Reference List
1.
Autism spectrum disorders. 1 ed. New York, NY: Oxford University Press; 2011.
Ref ID: 7097
2.
Comorbidities in developmental disorders. London, U.K.: MacKeith Press; 2010.
Ref ID: 7096
3.
Special report: aCGH for the genetic evaluation of patients with developmental
delay/mental retardation or autism spectrum disorder. Technol Eval Cent Asses Program
Exec Summ 2009;23(10):1-5.
Ref ID: 6523
4.
Prevalence of autism spectrum disorders--autism and developmental disabilities monitoring
network, 14 sites, United States, 2002. MMWR Surveill Summ 2007;56(1):12-28.
Ref ID: 5273
Abstract: PROBLEM/CONDITION: Data from a population-based, multisite surveillance
network were used to determine the prevalence of autism spectrum disorders (ASDs)
among children aged 8 years in 14 areas of the United States and to describe the
characteristics of these children. REPORTING PERIOD: 2002. METHODS: Children aged
8 years were identified as having an ASD through screening and abstraction of evaluation
records at health facilities for all 14 sites and through information from psychoeducational
evaluations for special education services for 10 of the 14 sites. Case status was
determined through clinician review of data abstracted from the records. Children whose
parent(s) or legal guardian(s) resided in the respective areas in 2002 and whose records
documented behaviors consistent with the Diagnostic and Statistical Manual, Fourth
Edition, Text Revision (DSM-IV-TR) criteria for autistic disorder; pervasive developmental
disorder, not otherwise specified; or Asperger disorder were classified as having ASDs.
RESULTS: For 2002, of 407,578 children aged 8 years in the 14 surveillance areas, 2,685
(0.66%) were identified as having an ASD. ASD prevalence per 1,000 children aged 8
years ranged from 3.3 (Alabama) to 10.6 (New Jersey), with the majority of sites ranging
from 5.2 to 7.6 (overall mean: 6.6 [i.e., one of every 152 children across all sites). ASD
prevalence was significantly lower than all other sites in Alabama (p<0.001) and higher in
New Jersey (p<0.0001). ASD prevalence varied by identification source, with higher
average prevalence for ASDs in sites with access to health and education records (mean:
7.2) compared with sites with health records only (mean: 5.1). Five sites identified a higher
prevalence of ASDs for non-Hispanic white children than for non-Hispanic black children.
The ratio of males to females ranged from 3.4:1.0 in Maryland, South Carolina, and
Wisconsin to 6.5:1.0 in Utah. The majority of children were receiving special education
services at age 8 years and had a documented history of concerns regarding their
development before age 3 years. However, the median age of earliest documented ASD
diagnosis was much later (range: 49 months [Utah]--66 months [Alabama]). The proportion
of children with characteristics consistent with the criteria for an ASD classification who had
a previously documented ASD classification varied across sites. In the majority of sites,
females with an ASD were more likely than males to have cognitive impairment. For the six
sites for which prevalence data were available from both 2000 and 2002, ASD prevalence
was stable in four sites and increased in two sites (17% in Georgia and 39% in West
Virginia). INTERPRETATION: Results from the second report of a U.S. multisite
collaboration to monitor ASD prevalence demonstrated consistency of prevalence in the
majority of sites, with variation in two sites. Prevalence was stable in the majority of sites
for which 2 years of data were available, but an increase in West Virginia and a trend
toward an increase in Georgia indicate the need for ongoing monitoring of ASD prevalence.
PUBLIC HEALTH ACTIONS: These ASD prevalence data provide the most complete
information on the prevalence of the ASDs in the United States to date. The data confirm
that ASD prevalence is a continuing urgent public health concern affecting an approximate
average of one child in every 150 and that efforts are needed to improve early identification
of ASDs
5.
Everything everyone needs to know about epigenetics. Einstein Quarterly
2006;(Spring):24-31.
Ref ID: 4978
6.
Mental health in the United States: parental report of diagnosed autism in children aged
4-17 years--United States, 2003-2004. MMWR Morb Mortal Wkly Rep
2006;55(17):481-486.
Ref ID: 5266
Abstract: Autism is a lifelong neurodevelopmental disorder characterized by early onset of
impairments in social interaction and communication and unusual, stereotyped behaviors.
Autism (i.e., autistic disorder) often is classified with two related, although less severe,
developmental disorders: Asperger disorder and pervasive developmental disorder--not
otherwise specified. These three constitute the autism spectrum disorders (ASDs).
Diagnosis of ASDs is based exclusively on developmental pattern and behavioral
observation. Two population-based studies conducted by CDC in selected U.S. locations
reported ASD prevalence of 3.4 and 6.7 per 1,000 children, respectively. CDC also
conducts two nationally representative surveys, the National Health Interview Survey
(NHIS) and the National Survey of Children's Health (NSCH), in which parents are asked
whether their child ever received a diagnosis of autism. Because of similarities in
methodology used by the two surveys, CDC analyzed 2003-2004 data from NHIS and data
from the first-ever NSCH (collected during January 2003-July 2004) to 1) estimate the
population-based prevalence of parental report of diagnosed autism in the United States
and 2) assess parental reporting of child social, emotional, and behavioral strengths and
difficulties and special-health care needs among children with and without reported autism.
This report describes the results of that analysis, which indicated that the prevalence of
parent-reported diagnosis of autism was 5.7 per 1,000 children in NHIS and 5.5 per 1,000
children in NSCH. Prevalence estimates in the two studies were similar across age, sex,
and racial/ethnic populations. The consistency in estimates between the two surveys
suggests high reliability for parental report of autism. These estimates suggest that, as of
2003-2004, autism had been diagnosed in at least 300,000 U.S. children aged 4-17 years.
In addition, parental reports of autism were associated with reported social, emotional, and
behavioral symptoms and specialized needs. Thus, these surveys might be useful to
assess health, education, and social service needs of children with autism
7.
Technical Report: The Pediatrician's Role in the Diagnosis and Management of Autistic
Spectrum Disorder in Children. Pediatrics 2001;107(5):E85.
Ref ID: 3362
Abstract: Autism and its milder variants are not rare. Most pediatricians will have the
opportunity to provide a medical home for a child with autism. This technical report serves
to complement and expand on the information in the accompanying policy statement to
increase the pediatrician's fund of knowledge and comfort level in caring for children with
autism. In so doing, it is anticipated that earlier diagnosis and referral for appropriate
intervention will be possible and that this will, in turn, have a positive effect on long-term
outcomes for children with autism and their families
8.
Developmental surveillance and screening of infants and young children. Pediatrics
2001;108(1):192-196.
Ref ID: 4194
Abstract: Early identification of children with developmental delays is important in the
primary care setting. The pediatrician is the best-informed professional with whom many
families have contact during the first 5 years of a child's life. Parents look to the pediatrician
to be the expert not only on childhood illnesses but also on development. Early intervention
services for children from birth to 3 years of age and early childhood education services for
2
children 3 to 5 years of age are widely available for children with developmental delays or
disabilities in the United States. Developmental screening instruments have improved over
the years, and instruments that are accurate and easy to use in an office setting are now
available to the pediatrician. This statement provides recommendations for screening
infants and young children and intervening with families to identify developmental delays
and disabilities
9.
Patient-based approaches to cognitive neuroscience. Cambridge MA: MIT Press; 2000.
Ref ID: 3382
10.
Reading and Attention Disorders. Baltimore MD: York Press; 1999.
Ref ID: 3340
11.
Practice parameters for the assessment and treatment of children and adolescents with
language and learning disorders. J Am Acad Child Adolesc Psychiatry 1998;37(10
Supplement):46S-62S.
Ref ID: 3026
12.
Textbook of Pediatric Neuropsychiatry. 1 ed. Washington D.C.: American Psychiatric
Press; 1998.
Ref ID: 3118
13.
Hearing Loss. New York: Thieme; 1997.
Ref ID: 1754
14.
Dyslexia. Sci Amer 1996;275(5):98-104.
Ref ID: 2059
15.
From categorization to classification: a comparison among individuals with autism, mental
retardation, and normal development. J Abn Psychol 1995;43:601-609.
Ref ID: 3379
16.
Movement disorders 3. London: Butterworth; 1994.
Ref ID: 2677
17.
Nonverbal learning disabilities: the syndrome and the model. New York: Guilford Press;
1989.
Ref ID: 7462
18.
Quantitative Examination of Neurologic Functions. Volume I: Scientific Basis and Design of
Instrumented Tests. Volume II: Methodology for Test and Patient Assessments and Design
of a Computer-Automated System. Boca Raton FL: CRC Press; 1985.
Ref ID: 1322
19.
The neuropsychology of social-emotional learning disabilities. Arch Neurol
1983;40:461-462.
Ref ID: 4216
20.
Developmental learning disabilities of the right hemisphere: emotional, interpersonal, and
cognitive components. Arch Neurol 1983;40:463-468.
Ref ID: 4217
21.
Acquired Aphasia in Children. New York NY: Academic Press; 1981.
Ref ID: 713
3
22.
Speech and language characteristics of children with Prader-Willi syndrome. In: Holm VA,
Sulzbacher S, Pipes PL, editors. The Prader-Willi syndrome. Baltimore MD: University Park
Press; 1981:179-183.
Ref ID: 1580
23.
Sign and Culture: A Reader for Students of American Sign Language. Silver Spring, MD:
Linstok Press; 1980.
Ref ID: 572
24.
Acoustic Impedance and Admittance - The Measurement of Middle Ear Function.
Baltimore: Williams and Wilkins; 1976.
Ref ID: 809
25.
Electrocochleography. Baltimore: University Park Press; 1976.
Ref ID: 811
26.
Anatomic diagnosis of nonconductive deafness by physiological tests. Archives of
Otorhinolaryngology 1963;78:47-51.
Ref ID: 4215
27.
Examiner Manual for the Purdue Pegboard. Chicago, IL: Science Research Associates;
1948.
Ref ID: 3137
28.
AACAP. Summary of the practice parameters for the assessment amd treatment of children
and adolescents with language and learning disorders. J Am Acad Child Adolesc
Psychiatry 1998;37(10):1117-1119.
Ref ID: 3023
29.
AACAP. Practice parameters for the assessment and treatment of children and
adolescents with language and learning disorders. J Am Acad Child Adolesc Psychiatry
1998;37(10 Supplement):46S-62S.
Ref ID: 3024
30.
Abbassi V, Linscheid T, Coleman M. Triiodothyronine (T3) concentration and therapy in
autistic children. Journal of Autism & Childhood Schizophrenia 1978;8(4):383-387.
Ref ID: 2251
Abstract: The clinical and biochemical status of thyroid function of patients with an autistic
syndrome was investigated. The study consisted of 13 patients between the ages of 7 and
21 years. There was no clinical evidence for hypothyroidism in any patient, and T3, T4, and
TSH concentrations were within the normal range. Two patients who had retarded bone
ages were treated with triiodothyronine for 6 months. Hyperthyroidism developed when T3
levels exceeded physiologic concentrations in these patients. The concept that the clinical
response to triiodothyronine in autistic patients results from correction of thyroid dysfunction
is not supported by these findings
31.
Abbeduto L, Furman L, Davies B. Relation between the receptive language and mental age
of persons with mental retardation. Am J Ment Retard 1989;93(5):535-543.
Ref ID: 2794
Abstract: The purpose of this study was to determine whether the development of receptive
language lags behind nonverbal cognitive development in school age persons with mental
retardation. The relation between receptive language and nonverbal MA was examined as
a function of MA level and the linguistic form to be understood. Individual differences in the
receptive language-MA relation were also investigated. Results indicated that the relation
4
between receptive language and MA varied across MA levels, linguistic forms, and
individuals at the same MA for listeners with mental retardation
32.
Abdul-Rahman OA, Hudgins L. The diagnostic utility of a genetics evaluation in children
with pervasive developmental disorders. Genet Med 2006;8(1):50-54.
Ref ID: 6618
Abstract: PURPOSE: A genetics evaluation of children with pervasive developmental
disorders (PDDs) identifies a diagnosis in 6% to 15% of cases. However, previous studies
have not measured the incidence of genetic disorders among children with autistic-like
features who do not necessarily meet the Diagnostic and Statistical Manual for Mental
Disorders, Fourth Edition criteria for PDD. METHODS: We identified 101 patients at our
institution referred for PDD, autism, Asperger syndrome, or autistic features. Seventy-eight
were males and 23 were females, giving a male-to-female ratio of 3.4:1. No diagnosis was
identified on examination alone, although Rett syndrome was suspected in six females.
Seventeen patients did not undergo any type of testing because of noncompliance.
RESULTS: Of the remaining 84 patients analyzed, seven (8.3%) were found to have
abnormalities on testing. Three chromosomal anomalies were found: one with 5p
duplication, one with low-level mosaicism for trisomy 21, and one with an unbalanced 10;22
translocation. Three females were diagnosed with Rett syndrome after MECP2 analysis
identified a disease-causing mutation. The remaining patient was found to have an
elevated urine orotic acid, with a normal ammonia level, of unknown significance.
CONCLUSION: On the basis of our series, the yield of a genetics evaluation in patients
with features of PDD who do not necessarily meet the Diagnostic and Statistical Manual for
Mental Disorders, Fourth Edition criteria is 8.3%. Approximately half of these were the
result of a chromosomal abnormality. Three cases of Rett syndrome were identified for
which autistic behaviors are a well-described feature. These findings suggest that a
high-resolution karyotype provides the greatest diagnostic yield for patients with autistic-like
features. MECP2 analysis should be considered for females who present with autistic
behaviors
33.
Abe K, Inokawa M, Kashiwagi A, Yanagihara T. Amnesia after a discrete basal forebrain
lesion. J Neurol Neurosurg Psychiatry 1998;65(1):126-130.
Ref ID: 2291
Abstract: Destructive lesions of the basal forebrain are often associated with memory
impairment and this structure is thought to contribute to memory function by providing a
cholinergic input to critical structures associated with memory such as the hippocampus
and amygdala. In previously reported cases of amnesia associated with damage in the
basal forebrain, multiple neuroanatomical regions were damaged, and the critical lesion
responsible for amnesia has not been identified clearly. We report a patient who developed
primarily anterograde amnesia after clipping of an unruptured anterior communicating
artery aneurysm. Postoperative magnetic resonance imaging showed a discrete lesion,
centering in the right diagonal band of Broca and including the anterior hypothalamus,
septal nucleus, lamina terminalis, and paraterminal gyrus, and an indiscrete patchy lesion
in the corresponding area on the opposite side. The nucleus basalis of Meynert was
minimally affected and the diencephalon was not damaged. Single photon emission
computed tomography showed marked hypoperfusion in the midline frontobasal region
corresponding to the MRI lesion and hypoperfusion in the hippocampus bilaterally. It is
concluded that disconnection of the pathway between the diagonal band of Broca and the
hippocampus contributed to memory impairment
34.
Abe K, Oda N, Amatomi M. Natural history and predictive significance of head-banging,
head-rolling and breath-holding spells. Dev Med Child Neurol 1984;26(5):644-648.
Ref ID: 3965
Abstract: A five-year follow-up study of children who had had spells of head-banging or
breath-holding at three years was carried out to see whether these symptoms have any
behavioural sequelae. Of 36 children with breath-holding spells at three years, none still
5
had them. 34 children had had spells of head-banging, and three still had the symptom at
follow-up. The children with a history of head-banging were more restless and emotionally
unstable at follow-up, but there was no significant difference between the index groups and
their controls in other problems of behaviour or development
35.
Abel KM, Drake R, Goldstein JM. Sex differences in schizophrenia. Int Rev Psychiatry
2010;22(5):417-428.
Ref ID: 7081
Abstract: Evidence suggests sex differences in schizophrenia reflect differences in both
neurodevelopmental processes and social effects on disease risk and course. Male:female
incidence approximates 1.4:1 but at older onset women predominate. Prevalence
differences appear smaller. Men have poorer premorbid adjustment and present with worse
negative and less depressive symptoms than women, which may explain their worse
medium term outcome according to a range of measures. Substance abuse is a
predominantly male activity in this group, as elsewhere. Findings of sex differences in brain
morphology are inconsistent but occur in areas that normally show sexual dimorphism,
implying that the same factors are important drivers of sex differences in both normal
neurodevelopmental processes and those associated with schizophrenia. There are sex
differences in antipsychotic responses but sex-specific endocrine effects on illness and
response to antipsychotics are potentially complex. Oestrogen's role as an adjunctive
medication is not yet clear due to methodological differences between the few randomized
controlled trials. Services that are sensitive to differences in gender can better meet their
patients' specific needs and potentially improve outcome
36.
Abell F, Krams M, Ashburner J et al. The neuroanatomy of autism: a voxel-based whole
brain analysis of structural scans. Neuroreport 1999;10(8):1647-1651.
Ref ID: 3325
Abstract: Autism is a biological disorder which affects social cognition, and understanding
brain abnormalities of the former will elucidate the brain basis of the latter. We report
structural MRI data on 15 high- functioning individuals with autistic disorder. A voxel-based
whole brain analysis identified grey matter differences in an amygdala centered system
relative to 15 age- and IQ-matched controls. Decreases of grey matter were found in
anterior parts of this system (right paracingulate sulcus, left inferior frontal gyrus). Increases
were found in posterior parts (amygdala/peri-amygdaloid cortex, middle temporal gyrus,
inferior temporal gyrus), and in regions of the cerebellum. These structures are implicated
in social cognition by animal, imaging and histopathological studies. This study therefore
provides converging evidence of the physiological basis of social cognition
37.
Aboitiz F, Scheibel AB, Zaidel E. Morphometry of the Sylvian fissure and the corpus
callosum, with emphasis on sex differences. Brain 1992;115(Pt 5):1521-1541.
Ref ID: 2787
Abstract: The relationship between anatomical asymmetries in the perisylvian region and
the sizes of different regions of the corpus callosum was investigated post-mortem in 40
brains of right-handed hospital admissions (20 males, 20 females) with no cortical
involvement. There were no sex differences either in anatomical asymmetries or in regional
size of the callosum. There was a negative correlation between the absolute value of
Sylvian fissure (planum temporale) asymmetries and the size of the isthmus in males but
not in females. Further, there was a significant negative correlation between the size of the
Sylvian fissure (or planum temporale) and the size of the callosal mid-body in males but not
in females. There was no correlation between the asymmetry of the planum temporale
magnitude of left-right and total size of the planum (left+right). These findings constrain
theories about the ontogenesis of hemispheric specialization through changes in callosal
connectivity and about sex differences in interhemispheric organization
38.
Abraham SS, Geschwind DH. Genetics of autism. In: Speicher MR, Antonarakis SE,
Motulsky AG, ., editors. Vogel and Moltusky's Human Genetics: Problems and Approaches
6
(4th Edition) ed. Berlin: Springer-Verlag; 2010:699-714.
Ref ID: 6604
39.
Abraham SS, Wallace IF, Gravel JS. Early otitis media and phonological development at
age 2 years. Laryngoscope 1996;106(6):727-732.
Ref ID: 1881
Abstract: The effect of early otitis media on phonology and articulation in the presence of
expressive language delay was investigated in 16 2-year-olds followed prospectively from
birth. Eight of the children were designated otitis-positive and 8 were considered
otitis-negative as determined by bilateral pneumatic otoscopy outcomes during year 1 of
life. The groups differed significantly on measures of expressive, not receptive, language
development. All members of the otitis-positive group were expressive language delayed.
Phonological analyses were completed on spoken language samples elicited from each
child at age 24 months. Results showed similar developmental tendencies in speech sound
acquisition between the groups, but the otitis-positive group had established significantly
fewer initial consonant phones and produced them less accurately than the otitis-negative
subject group. The otitis-positive group acquired significantly fewer consonants with back
place of articulation. Similar phonological error patterns of deletion and phoneme class
deficiency were used by the groups, but the otitis-positive group used the error patterns
more frequently. Findings here lend support to the otitis media effect as one of interaction
among risk factors.
40.
Abrahams BS. Genetics: many roads to the autism spectrum disorders. In: Fein D, editor.
2010.
Ref ID: 6605
41.
Abrahams BS, Geschwind DH. Connecting genes to brain in the autism spectrum
disorders. Arch Neurol 2010;67(4):395-399.
Ref ID: 6668
Abstract: The autism spectrum disorders (ASDs) are a complex group of neuropsychiatric
conditions involving language, social communication, and mental flexibility. Here, we
attempt to place recent genetic advances within a developmental and anatomical context.
Recent progress in identifying ASD candidate genes supports involvement of multiple brain
regions, including the frontal lobes, anterior temporal lobes, caudate, and cerebellum.
Understanding genetic data within an anatomical context will be critical to explain how
individual risk factors operate to shape phenotypic presentation in patients
42.
Abrahams BS, Geschwind DH. Genetics of Autism. In: Speicher MR, ntonarakis SE,
otulsky AG, editors. 4 ed. Berlin: Springer-Verlag; 2010:700-714.
Ref ID: 6865
43.
Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new
neurobiology. Nat Rev Genet 2008;9(5):341-355.
Ref ID: 5825
Abstract: Autism is a heterogeneous syndrome defined by impairments in three core
domains: social interaction, language and range of interests. Recent work has led to the
identification of several autism susceptibility genes and an increased appreciation of the
contribution of de novo and inherited copy number variation. Promising strategies are also
being applied to identify common genetic risk variants. Systems biology approaches,
including array-based expression profiling, are poised to provide additional insights into this
group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a
dominant theme
44.
Abrahams BS, Tentler D, Perederiy JV, Oldham MC, Coppola G, Geschwind DH.
Genome-wide analyses of human perisylvian cerebral cortical patterning. Proc Natl Acad
Sci U S A 2007;104(45):17849-17854.
7
Ref ID: 5415
Abstract: Despite the well established role of the frontal and posterior perisylvian cortices in
many facets of human-cognitive specializations, including language, little is known about
the developmental patterning of these regions in the human brain. We performed a
genome-wide analysis of human cerebral patterning during midgestation, a critical epoch in
cortical regionalization. A total of 345 genes were identified as differentially expressed
between superior temporal gyrus (STG) and the remaining cerebral cortex. Gene ontology
categories representing transcription factors were enriched in STG, whereas cell-adhesion
and extracellular matrix molecules were enriched in the other cortical regions. Quantitative
RT-PCR or in situ hybridization was performed to validate differential expression in a
subset of 32 genes, most of which were confirmed. LIM domain-binding 1 (LDB1), which
we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4
(LMO4), a gene known to be involved in the asymmetric pattering of the perisylvian
region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell
adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex.
Contactin associated protein-like 2 (CNTNAP2), in which mutations are known to cause
autism, epilepsy, and language delay, showed a remarkable pattern of anterior-enriched
cortical expression in human that was not observed in mouse or rat. These data highlight
the importance of expression analysis of human brain and the utility of cross-species
comparisons of gene expression. Genes identified here provide a foundation for
understanding molecular aspects of human-cognitive specializations and the disorders that
disrupt them
45.
Abrajano JJ, Qureshi IA, Gokhan S, Zheng D, Bergman A, Mehler MF. REST and CoREST
modulate neuronal subtype specification, maturation and maintenance. PLoS One
2009;4(12):e7936.
Ref ID: 6637
Abstract: BACKGROUND: The repressor element-1 silencing transcription
factor/neuron-restrictive silencer factor (REST/NRSF) is a master regulator of neuronal
gene expression. REST functions as a modular scaffold for dynamic recruitment of
epigenetic regulatory factors including its primary cofactor, the corepressor for
element-1-silencing transcription factor (CoREST), to genomic loci that contain the
repressor element-1 (RE1) binding motif. While REST was initially believed to silence RE1
containing neuronal genes in neural stem cells (NSCs) and non-neuronal cells, emerging
evidence shows an increasingly complex cell type- and developmental stage-specific
repertoire of REST target genes and functions that include regulation of neuronal lineage
maturation and plasticity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
utilized chromatin immunoprecipitation on chip (ChIP-chip) analysis to examine REST and
CoREST functions during NSC-mediated specification of cholinergic neurons (CHOLNs),
GABAergic neurons (GABANs), glutamatergic neurons (GLUTNs), and medium spiny
projection neurons (MSNs). We identified largely distinct but overlapping profiles of REST
and CoREST target genes during neuronal subtype specification including a
disproportionately high percentage that are exclusive to each neuronal subtype.
CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that the differential deployment
of REST and CoREST is an important regulatory mechanism that mediates neuronal
subtype specification by modulating specific gene networks responsible for inducing and
maintaining neuronal subtype identity. Our observations also implicate a broad array of
factors in the generation of neuronal diversity including but not limited to those that mediate
homeostasis, cell cycle dynamics, cell viability, stress responses and epigenetic regulation
46.
Abu-Elneel K, Liu T, Gazzaniga FS et al. Heterogeneous dysregulation of microRNAs
across the autism spectrum. Neurogenetics 2008;9(3):153-161.
Ref ID: 5823
Abstract: microRNAs (miRNAs) are ~21 nt transcripts capable of regulating the expression
of many mRNAs and are abundant in the brain. miRNAs have a role in several complex
diseases including cancer as well as some neurological diseases such as Tourette's
8
syndrome and Fragile x syndrome. As a genetically complex disease, dysregulation of
miRNA expression might be a feature of autism spectrum disorders (ASDs). Using
multiplex quantitative polymerase chain reaction (PCR), we compared the expression of
466 human miRNAs from postmortem cerebellar cortex tissue of individuals with ASD (n =
13) and a control set of non-autistic cerebellar samples (n = 13). While most miRNAs levels
showed little variation across all samples suggesting that autism does not induce global
dysfunction of miRNA expression, some miRNAs among the autistic samples were
expressed at significantly different levels compared to the mean control value. Twenty-eight
miRNAs were expressed at significantly different levels compared to the non-autism control
set in at least one of the autism samples. To validate the finding, we reversed the analysis
and compared each non-autism control to a single mean value for each miRNA across all
autism cases. In this analysis, the number of dysregulated miRNAs fell from 28 to 9
miRNAs. Among the predicted targets of dysregulated miRNAs are genes that are known
genetic causes of autism such Neurexin and SHANK3. This study finds that altered miRNA
expression levels are observed in postmortem cerebellar cortex from autism patients, a
finding which suggests that dysregulation of miRNAs may contribute to autism spectrum
phenotype
47.
Abutalebi J, Annoni JM, Zimine I et al. Language Control and Lexical Competition in
Bilinguals: An Event-Related fMRI Study. Cereb Cortex 2007.
Ref ID: 5432
Abstract: Language selection (or control) refers to the cognitive mechanism that controls
which language to use at a given moment and context. It allows bilinguals to selectively
communicate in one target language while minimizing the interferences from the nontarget
language. Previous studies have suggested the participation in language control of different
brain areas. However, the question remains whether the selection of one language among
others relies on a language-specific neural module or general executive regions that also
allow switching between different competing behavioral responses including the switching
between various linguistic registers. In this functional magnetic resonance imaging study,
we investigated the neural correlates of language selection processes in German-French
bilingual subjects during picture naming in different monolingual and bilingual selection
contexts. We show that naming in the first language in the bilingual context (compared with
monolingual contexts) increased activation in the left caudate and anterior cingulate cortex.
Furthermore, the activation of these areas is even more extended when the subjects are
using a second weaker language. These findings show that language control processes
engaged in contexts during which both languages must remain active recruit the left
caudate and the anterior cingulate cortex (ACC) in a manner that can be distinguished from
areas engaged in intralanguage task switching
48.
Accardo P, Morrow J, Heaney MS, Whitman B, Tomazic T. Toe walking and language
development. Clin Pediatr (Phila) 1992;31(3):158-160.
Ref ID: 3935
Abstract: Neurodevelopmental markers that are present early in childhood may identify
children at risk for later developmental disabilities. This paper attempts to clarify the
relationship between one such proposed marker, toe walking, and language development
in a general pediatric population. One hundred sixty-three children being seen for well-child
visits were included in the study. Information from each child's caretaker was obtained for
language development and a history of toe walking; observation of toe walking during the
visit was also included. The frequency of toe walking was 24%. Language quotients were
calculated and compared for toe walkers (n = 39) and non-toe walkers (n = 127). The mean
language quotient for toe walkers tended to be consistently lower than that for non-toe
walkers. The specificity of toe walking for low language scores was 85% but had a
sensitivity of only 32%. Although an association between toe walking and language delay is
supported by the present data, the association does not appear to be clinically significant
9
49.
Accardo P, Whitman B. Toe walking. A marker for language disorders in the
developmentally disabled. Clin Pediatr (Phila) 1989;28(8):347-350.
Ref ID: 3936
Abstract: Toe walking unassociated with an autistic disorder or cerebral palsy generally has
been considered a normal infant gait. The incidence of toe walking in various diagnostic
subgroups of 799 developmentally disabled children presenting to a tertiary-level
multidisciplinary assessment clinic was reviewed to investigate the authors' clinical
impression that toe walking may be a marker for language dysfunction. Toe walking was
found to be more frequent in those diagnostic subgroups with more severe language
disorders. Toe walking also correlated with lower IQ scores (p less than 0.0001). The
sensitivities, specificities, predictive validities and odds ratios all supported the
hypothesized association between toe walking and language disorders. Further prospective
studies of the neurodevelopmental outcome of children with toe walking are needed to
determine whether this behavior can identify children at risk for language disorders
50.
Achenbach TM, McConaughy SM, Howell CT. Child/adolescent behavioral and emotional
problems: Implications of cross-informant correlations for situational specificity. Psychol
Bull 1987;101(2):213-232.
Ref ID: 415
51.
Achenbach TM, Edelbrock CS. Manual for the Child Behavior Checklist and Revised
Profile. Burlington VT: University of Vermont, Department of Psychiatry; 1983.
Ref ID: 1424
52.
Acosta MT, Pearl PL. The neurobiology of autism: new pieces of the puzzle. Curr Neurol
Neurosci Rep 2003;3(2):149-156.
Ref ID: 3912
Abstract: The neurobiologic basis of autism is reviewed, with discussion of evidence from
genetic, magnetic resonance imaging, neuropathology, and functional neuroimaging
studies. Although autism is a behaviorally valid syndrome, it is remarkably heterogeneous
and involves multiple developmental domains as well as a wide range of cognitive,
language, and socioemotional functioning. Although multiple etiologies are implicated,
recent advances have identified common themes in pathophysiology. Genetic factors play
a primary role, based on evidence from family studies, identification of putative genes using
genome-wide linkage analyses, and comorbidities with known genetic mutations. The
RELN gene, which codes for an extracellular protein guiding neuronal migration, has been
implicated in autism. Numerous neuropathologic changes have been described, including
macroencephaly, acceleration and then deceleration in brain growth, increased neuronal
packing and decreased cell size in the limbic system, and decreased Purkinje cell number
in the cerebellum. Abnormalities in organization of the cortical minicolumn, representing the
fundamental subunit of vertical cortical organization, may underlie the pathology of autism
and result in altered thalamocortical connections, cortical disinhibition, and dysfunction of
the arousal-modulating system of the brain. The role of acquired factors is speculative, with
insufficient evidence to link the measles-mumps-rubella (MMR) vaccine with autism or to
change immunization practices
53.
Adab N, Kini U, Vinten J et al. The longer term outcome of children born to mothers with
epilepsy. J Neurol Neurosurg Psychiatry 2004;75(11):1575-1583.
Ref ID: 5478
Abstract: OBJECTIVES: To determine the prevalence of cognitive delay and possible
associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero.
DESIGN: Retrospective study of children born to mothers with epilepsy. SETTING:
Regional epilepsy clinics in Liverpool and Manchester, UK. PARTICIPANTS: Children aged
between 6 months and 16 years born to mothers with epilepsy. MAIN OUTCOME
MEASURES: Structured interviews, hospital records, clinical examination, and
psychometric tests (Wechsler) were used to assess exposure and intelligence quotient
10
(IQ). Blinded assessment of photographs was used to score children with characteristic
dysmorphic features. RESULTS: A total of 249 children aged 6 and over were studied: 41
were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to
polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the
valproate group compared to unexposed and other monotherapy groups. Multiple
regression analysis showed that both valproate exposure and frequent tonic-clonic seizures
in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other
confounding factors. There was a significant negative correlation between dysmorphic
features and verbal IQ in children exposed to valproate. CONCLUSIONS: This study
identifies valproate as a drug carrying potential risks for developmental delay and cognitive
impairment and is the first to suggest that frequent tonic-clonic seizures have a similar
effect. Our results need to be interpreted with caution given their retrospective nature.
Women with epilepsy need careful counselling about individual risk benefit of AED
treatment before pregnancy
54.
Adachi M, Kawanami T, Ohshima F, Hosoya T. MR findings of cerebral white matter in
Cockayne syndrome. Magn Reson Med Sci 2006;5(1):41-45.
Ref ID: 5734
Abstract: The characteristic magnetic resonance (MR) findings of Cockayne syndrome
have been reported; however, the corresponding characteristics on diffusion-weighted and
fluid-attenuated inversion recovery (FLAIR) imaging are yet to be documented. In this adult
case with Cockayne syndrome, we identified small patchy subcortical lesions visualized as
areas of high intensity on diffusion-weighted images and low intensity on FLAIR images. It
is possible that these findings reflect active demyelinating lesions
55.
Adams AM, Gathercole SE. Limitations in working memory: implications for language
development. Int J Lang Commun Disord 2000;35(1):95-116.
Ref ID: 3216
Abstract: In this study, the proposal that individual differences in spoken language
acquisition may be due to limitations in short-term memory abilities was investigated within
a working memory framework. The relationship speech production skills and working
memory abilities was examined in two groups of 4-year-old children, matched for
non-verbal ability but who had either relatively good or poor non-word repetition skills.
Children with better non-word repetition skills produced speech that comprised a wider
repertoire of words, on average longer utterances and a greater range of syntactic
constructions than did children with relatively poor non-word repetition skills. The significant
association found between these indices of language development and verbal short-term
memory span assessed with non-spoken recall, suggested that this relationship was not
merely due to the common output requirements of the language and memory tasks.
Inconsistent associations between language performance and two tasks of visuo-spatial
short-term memory precluded firm conclusions being drawn regarding the specificity of the
relationship to the phonological domain. Cognitive mechanisms that may underlie the
association between spoken language development and working memory skills are
discussed
56.
Adams C, Bishop DV. Conversational characteristics of children with semantic-pragmatic
disorder. I: Exchange structure, turntaking, repairs and cohesion. Brit J Disord Communic
1989;24(3):211-239.
Ref ID: 4623
Abstract: Conversational samples were obtained from 57 children aged from 8 to 12 years
with specific language impairment, and 67 control children aged from 4 to 12 years.
Fourteen of the language-impaired children fitted the clinical description of
semantic-pragmatic disorder. It was found that exchange structure, turntaking,
conversational repair and use of cohesive devices could be assessed with adequate
inter-rater and test-retest reliability. Children with semantic-pragmatic disorder produced
more initiations than other children. Some of these children also violated turntaking rules by
11
interrupting the conversational partner to an unusual degree. Use of cohesion was normal
for children with semantic-pragmatic disorder, but limited in other language-impaired
children. Analysis of conversations may be more useful than conventional language tests
for identifying linguistic abnormalities in children with semantic-pragmatic disorder
57.
Adams NA, Awadein A, Toma HS. The retinal ciliopathies. Ophthalmic Genet
2007;28(3):113-125.
Ref ID: 6163
Abstract: While the functions of many of the proteins located in or associated with the
photoreceptor cilia are poorly understood, disruption of the function of these proteins may
result in a wide variety of phenotypes ranging from isolated retinal degeneration to more
pleiotropic phenotypes. Systemic findings include neurosensory hearing loss,
developmental delay, situs-inversus, infertility, disorders of limb and digit development,
obesity, kidney disease, liver disease, and respiratory disease. The concept of "retinal
ciliopathies" brings to attention the importance of further molecular analysis of this
organelle as well as provides a potential common target for therapies for these disorders.
The retinal ciliopathies include retinitis pigmentosa, macular degeneration, cone-dystrophy,
cone-rod dystrophy, Leber congenital amaurosis, as well as retinal degenerations
associated with Usher syndrome, primary ciliary dyskinesia, Senior-Loken syndrome,
Joubert syndrome, Bardet-Biedl syndrome, Laurence-Moon syndrome, McKusick-Kaufman
syndrome, and Biemond syndrome. Mutations for these disorders have been found in
retinitis pigmentosa-1 (RP1), retinitis pigmentosa GTPase regulator (RPGR), retinitis
pigmentosa GTPase regulator interacting protein (RPGR-IP), as well as the Usher,
Bardet-Biedl, and nephronophthisis genes. Other systemic disorders associated with retinal
degenerations that may also involve ciliary abnormalities include: Alstrom, Edwards-Sethi,
Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes.
Understanding these conditions as ciliopathies may help the ophthalmologist to recognize
associations between seemingly unrelated diseases and have a high degree of suspicion
that a systemic finding may be present
58.
Addington AM, Rapoport JL. Annual research review: impact of advances in genetics in
understanding developmental psychopathology. J Child Psychol Psychiatry
2012;53(5):510-518.
Ref ID: 7291
Abstract: It was hoped that diagnostic guidelines for, and treatment of, child psychiatric
disorders in DSM-5 would be informed by the wealth of clinical genetic research related to
neurodevelopmental disorders. In spite of remarkable advances in genetic technology, this
has not been the case. Candidate gene, genome-wide association, and rare copy number
variant (CNV) studies have been carried out for attention-deficit/hyperactivity disorder
(ADHD), Autism, Tourette's Syndrome, and schizophrenia, with intriguing results, but
environmental factors, incomplete penetrance, pleiotropy, and genetic heterogeneity,
underlying any given phenotype have limited clinical translation. One promising approach
may be the use of developmental brain imaging measures as more relevant phenotypes.
This is particularly important, as subtle abnormalities in timing and expression of gene
pathways underlying brain development may well link these disorders and be the ultimate
target of treatments
59.
Adler S. The Non-Verbal Child. Springfield, IL: Charles C. Thomas; 1964.
Ref ID: 898
60.
Adrien JL, Lenoir P, Martineau J, Perrot A, Hameury L, Larmande C. Blind ratings of early
symptoms of autism based on family home movies. J Am Acad Child Adolesc Psychiatry
1993;32:617-626.
Ref ID: 1593
12
61.
Aeby A, DeTiege X, Creuzil M et al. Language development at 2 years is correlated to brain
microstructure in the left superior temporal gyrus at term equivalent age: a diffusion tensor
imaging study. Neuroimage 2013;78:145-151.
Ref ID: 7776
Abstract: This study aims at testing the hypothesis that neurodevelopmental abilities at age
2 years are related with local brain microstructure of preterm infants at term equivalent age.
Forty-one preterm infants underwent brain MRI with diffusion tensor imaging sequences to
measure mean diffusivity (MD), fractional anisotropy (FA), longitudinal and transverse
diffusivity (lambda// and lambda[perpendicular]) at term equivalent age. Neurodevelopment
was assessed at 2 years corrected age using the Bayley III scale. A voxel-based analysis
approach, statistical parametric mapping (SPM8), was used to correlate changes of the
Bayley III scores with the regional distribution of MD, FA, lambda// and
lambda[perpendicular]. We found that language abilities are negatively correlated to MD,
lambda// and lambda[perpendicular] in the left superior temporal gyrus in preterm infants.
These findings suggest that higher MD, lambda// and lambda[perpendicular] values at
term-equivalent age in the left superior temporal gyrus are associated with poorer language
scores in later childhood. Consequently, it highlights the key role of the left superior
temporal gyrus for the development of language abilities in children. Further studies are
needed to assess on an individual basis and on the long term the prognostic value of brain
DTI at term equivalent age for the development of language
62.
Afif A, Bouvier R, Buenerd A, Trouillas J, Mertens P. Development of the human fetal
insular cortex: study of the gyration from 13 to 28 gestational weeks. Brain Struct Funct
2007;212(3-4):335-346.
Ref ID: 5865
Abstract: To describe the morphological stages of insular sulci and gyri development we
carried out a macroscopical study on 21 human fetal brains, showing no anomalies, from
13 to 28 gestational weeks (GWs). Particular focus was given to morphological appearance
during the development of insular and periinsular structures, especially the gyration and
sulcation of the insula, central cerebral region and opercula, as well as the vascularization
of these regions. The periinsular sulci and the central (insular and cerebral) sulci were the
first macroscopical structures identified on the lateral surface of the human fetal cerebral
hemisphere with earlier development on the right hemisphere. Here we describe five
stages of insular gyral and sulcal development closely related to gestational age: stage 1:
appearance of the first sulcus at 13-17 GWs, stage 2: development of the periinsular sulci
at 18-19 GWs, stage 3: central sulci and opercularization of the insula at 20-22 GWs, stage
4: covering of the posterior insula at 24-26 GWs, stage 5: closure of the sylvian fissure at
27-28 GWs. We provide evidence that cortical maturation (sulcation and gyration) and
vascularization of the lateral surface of the brain starts with the insular region, suggesting
that this region is a central area of cortical development
63.
Afifi AK, Uc EY. Cortical-subcorical circuitry for movement, cognition, and behavior. In:
Coffey CE, Brumback RA, editors. Textbook of Pediatric Neuropsychiatry. 1 ed.
Washington DC: American Psychiatric Press; 1998:65-100.
Ref ID: 2450
64.
Afzal MA, Pipkin PA, Minor PD. Absence of chicken myelin basic protein residues in
commercial formulations of MMR vaccine. Vaccine 2000;19(4-5):442-446.
Ref ID: 3657
Abstract: Several preparations of MMR vaccines and their progenitor monovalent vaccine
bulks produced by two different manufacturers were examined serologically for the
presence of chicken myelin basic protein (MBP) residues. The products were challenged
against several commercial preparations of anti-hMBP antisera that reacted positively with
the control MBP preparations of human and chicken origins. There was no evidence of the
presence of MBP components in MMR vaccines or their progenitor vaccine bulks as shown
by the reactivity profiles of the antibody preparations against control and test antigens
13
65.
Aggleton JP. Multiple anatomical systems embedded within the primate medial temporal
lobe: implications for hippocampal function. Neurosci Biobehav Rev 2012;36(7):1579-1596.
Ref ID: 7804
Abstract: A review of medial temporal lobe connections reveals three distinct groupings of
hippocampal efferents. These efferent systems and their putative memory functions are: (1)
The 'extended-hippocampal system' for episodic memory, which involves the anterior
thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular
cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for
affective and social learning, which involves prefrontal cortex, amygdala and nucleus
accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum;
(3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and
integration, which originates from the length of CA1 and the subiculum, and is
characterised by columnar, connections with reciprocal topographies. A fourth system, the
'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval
processing, has more widespread prefrontal connections than those of the hippocampus,
along with different thalamic inputs. Despite many interactions between these four systems,
they may retain different roles in memory which when combined explain the importance of
the medial temporal lobe for the formation of declarative memories
66.
Agrillo C, Piffer L. Musicians outperform nonmusicians in magnitude estimation: evidence
of a common processing mechanism for time, space and numbers. Q J Exp Psychol (Hove
) 2012;65(12):2321-2332.
Ref ID: 7668
Abstract: It has been proposed that time, space, and numbers may be computed by a
common magnitude system. Even though several behavioural and neuroanatomical studies
have focused on this topic, the debate is still open. To date, nobody has used the individual
differences for one of these domains to investigate the existence of a shared cognitive
system. Musicians are known to outperform nonmusicians in temporal discrimination tasks.
We therefore observed professional musicians and nonmusicians undertaking three
different tasks: temporal (participants were required to estimate which of two tones lasted
longer), spatial (which line was longer), and numerical discrimination (which group of dots
was more numerous). If time, space, and numbers are processed by the same mechanism,
it is expected that musicians will have a greater ability, even in nontemporal dimensions. As
expected, musicians were more accurate with regard to temporal discrimination. They also
gave better performances in both the spatial and the numerical tasks, but only outside the
subitizing range. Our data are in accordance with the existence of a common magnitude
system. We suggest, however, that this mechanism may not involve the whole numerical
range
67.
Aguirre LA, Perez-Bas M, Villamar M et al. A Spanish sporadic case of deafness-dystonia
(Mohr-Tranebjaerg) syndrome with a novel mutation in the gene encoding TIMM8a, a
component of the mitochondrial protein translocase complexes. Neuromuscul Disord
2008;18(12):979-981.
Ref ID: 6145
Abstract: Mohr-Tranebjaerg syndrome is a rare X-linked condition characterized by the
association of dystonia and progressive postlingual sensorineural hearing impairment. Here
we report the clinical and genetic findings in a Spanish patient with MTS carrying a novel
mutation in the DDP1 (deafness-dystonia peptide 1) gene, which encodes TIMM8a, a
component of the mitochondrial protein translocation system. The phenotypic variability
observed in patients with Mohr-Tranebjaerg syndrome suggests the involvement of modifier
factors which may modulate the clinical manifestations of the syndrome
68.
Ahlsen G, Rosengren L, Belfrage M et al. Glial fibrillary acidic protein in the cerebrospinal
fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry
1993;33(10):734-743.
Ref ID: 1455
14
69.
Ahmad Z, Balsamo LM, Sachs BC, Xu B, Gaillard WD. Auditory comprehension of
language in young children: neural networks identified with fMRI. Neurology
2003;60(10):1598-1605.
Ref ID: 4362
Abstract: OBJECTIVE: The organization of neuronal systems that process language in
young children is poorly understood. The authors used fMRI to identify brain regions
underlying auditory comprehension in healthy young children. METHODS: Fifteen
right-handed children (mean age 6.8 years) underwent fMRI at 1.5-T using blood oxygen
level dependent echoplanar imaging. They listened to stories with a reverse speech control
condition. Group data were analyzed with statistical parametric mapping. Individual subject
data were analyzed with a region of interest approach based on t-maps. An asymmetry
index (AI = [(L-R)/(L+R)]) was calculated for each region. RESULTS: Group analysis
showed significant activation in the left middle temporal gyrus (Brodmann area [BA] 21) and
left superior temporal gyrus (BA 22) along the superior temporal sulcus extending back to
the angular gyrus (BA 39). Individual maps showed lateralized activation in temporal
regions (AI > 0.49 +/- 0.39). There was minimal activation in the frontal lobe. There were no
significant correlations between age and regional AI. CONCLUSION: Networks for auditory
language processing are regionally localized and lateralized by age 5. These data may
provide a means to interpret language fMRI studies performed in preparation for brain
surgery, and may be employed to investigate the effect of chronic disease states, such as
epilepsy, on language organization during critical periods for plasticity
70.
Ahmed ZM, Riazuddin S, Khan SN, Friedman PL, Riazuddin S, Friedman TB. USH1H, a
novel locus for type I Usher syndrome, maps to chromosome 15q22-23. Clin Genet
2009;75(1):86-91.
Ref ID: 6159
Abstract: Usher syndrome (USH) is a hereditary disorder associated with sensorineural
hearing impairment, progressive loss of vision attributable to retinitis pigmentosa (RP) and
variable vestibular function. Three clinical types have been described with type I (USH1)
being the most severe. To date, six USH1 loci have been reported. We ascertained two
large Pakistani consanguineous families segregating profound hearing loss, vestibular
dysfunction, and RP, the defining features of USH1. In these families, we excluded linkage
of USH to the 11 known USH loci and subsequently performed a genome-wide linkage
screen. We found a novel USH1 locus designated USH1H that mapped to chromosome
15q22-23 in a 4.92-cM interval. This locus overlaps the non-syndromic deafness locus
DFNB48 raising the possibility that the two disorders may be caused by allelic mutations
71.
Ahmed ZM, Riazuddin S, Aye S et al. Gene structure and mutant alleles of PCDH15:
nonsyndromic deafness DFNB23 and type 1 Usher syndrome. Hum Genet
2008;124(3):215-223.
Ref ID: 6157
Abstract: Mutations of PCDH15, encoding protocadherin 15, can cause either combined
hearing and vision impairment (type 1 Usher syndrome; USH1F) or nonsyndromic deafness
(DFNB23). Human PCDH15 is reported to be composed of 35 exons and encodes a variety
of isoforms with 3-11 ectodomains (ECs), a transmembrane domain and a carboxy-terminal
cytoplasmic domain (CD). Building on these observations, we describe an updated gene
structure that has four additional exons of PCDH15 and isoforms that can be subdivided
into four classes. Human PCDH15 encodes three alternative, evolutionarily conserved
unique cytoplasmic domains (CD1, CD2 or CD3). Families ascertained on the basis of
prelingual hearing loss were screened for linkage of this phenotype to markers for PCDH15
on chromosome 10q21.1. In seven of twelve families segregating USH1, we identified
homozygous mutant alleles (one missense, one splice site, three nonsense and two
deletion mutations) of which six are novel. One family was segregating nonsyndromic
deafness DFNB23 due to a homozygous missense mutation. To date, in our cohort of 557
Pakistani families, we have found 11 different PCDH15 mutations that account for deafness
in 13 families. Molecular modeling provided mechanistic insight into the phenotypic
15
variation in severity of the PCDH15 missense mutations. We did not find pathogenic
mutations in five of the twelve USH1 families linked to markers for USH1F, which suggest
either the presence of mutations of yet additional undiscovered exons of PCDH15,
mutations in the introns or regulatory elements of PCDH15, or an additional locus for type I
USH at chromosome 10q21.1
72.
Ahmed ZM, Goodyear R, Riazuddin S et al. The tip-link antigen, a protein associated with
the transduction complex of sensory hair cells, is protocadherin-15. J Neurosci
2006;26(26):7022-7034.
Ref ID: 6291
Abstract: Sound and acceleration are detected by hair bundles, mechanosensory structures
located at the apical pole of hair cells in the inner ear. The different elements of the hair
bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One
of these links, the tip link, connects the top of a shorter stereocilium with the lateral
membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel
of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a
hitherto unidentified antigen specifically associated with the tip and kinocilial links of
sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as
an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness
Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to
be expressed in the mouse inner ear, and these define four major isoform classes, two with
entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three
cytoplasmic domain-containing isoform classes reveal that each has a different
spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms
are distributed in a manner compatible for association with the tip-link complex. An isoform
located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with
subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal
of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and
may be an integral component of this structure and/or required for its formation
73.
Ahmed ZM, Riazuddin S, Riazuddin S, Wilcox ER. The molecular genetics of Usher
syndrome. Clin Genet 2003;63(6):431-444.
Ref ID: 4056
Abstract: Association of sensorineural deafness and progressive retinitis pigmentosa with
and without a vestibular abnormality is the hallmark of Usher syndrome and involves at
least 12 loci among three different clinical subtypes. Genes identified for the more
commonly inherited loci are USH2A (encoding usherin), MYO7A (encoding myosin VIIa),
CDH23 (encoding cadherin 23), PCDH15 (encoding protocadherin 15), USH1C (encoding
harmonin), USH3A (encoding clarin 1), and USH1G (encoding SANS). Transcripts from all
these genes are found in many tissues/cell types other than the inner ear and retina, but all
are uniquely critical for retinal and cochlear cell function. Many of these protein products
have been demonstrated to have direct interactions with each other and perform an
essential role in stereocilia homeostasis
74.
Ahn MS, Breeze JL, Makris N et al. Anatomic brain magnetic resonance imaging of the
basal ganglia in pediatric bipolar disorder. J Affect Disord 2007;104(1-3):147-154.
Ref ID: 7091
Abstract: BACKGROUND: Basal ganglia (BG) enlargement has been found in studies of
adults with bipolar disorder (BPD), while the few studies of BPD youths have had mixed
findings. The BG (caudate, putamen, globus pallidus, nucleus accumbens) is
interconnected with limbic and prefrontal cortical structures and therefore may be
implicated in BPD. METHODS: Sixty-eight youths (46 with BPD, 22 healthy controls)
received neurological and psychiatric assessment, semi-structured interviews, and
neuropsychological testing, followed by anatomic magnetic resonance imaging on a 1.5
Tesla scanner. After image segmentation, log BG volumes and asymmetry indices were
analyzed using MANOVAs controlling for the effects of cerebral volume, age, sex, and
16
diagnosis. These omnibus tests were followed by univariate linear regression models of
each BG structure. RESULTS: Youths with BPD had a trend for larger right nucleus
accumbens (NA) volumes (p = 0.089). There were no significant group asymmetry
differences, nor volume differences in the caudate, putamen, and globus pallidus. When
analyzed separately by pubertal status, the prepubertal group had significantly larger total
NA (p = 0.035) versus healthy controls, while the pubertal group did not show significant
differences in the NA versus healthy controls. LIMITATIONS: The size of the control group
is relatively small, possibly limiting our power to detect significant group differences. The
inter-rater reliability for the NA is not as strong as the other structures; the finding of volume
differences in this structure is preliminary and warrants replication. CONCLUSIONS:
Youths with BPD had larger right NA volumes; this enlargement was most pronounced in
the prepubertal group. The differences between these findings and those seen in adult BPD
imply a neurodevelopmental phenomenon
75.
Aicardi J. Atypical semiology of rolandic epilepsy in some related syndromes. Epileptic
Disord 2000;2 Suppl 1:S5-S9.
Ref ID: 5388
Abstract: Atypical seizures, especially generalized or focal atonic attacks and atypical
absences may occur in association with the classical seizures of rolandic epilepsy. They
are often associated with unusual EEG features, especially a marked activation of
paroxysms during sleep that may amount to continuous spike-wave complexes of slow
sleep. These electroclinical features are often accompanied by cognitive and/or behavioral
disturbances and may belong to several syndromes (atypical benign partial epilepsy,
syndrome of continuous spike-waves during sleep, Landau-Kleffner syndrome and status of
rolandic epilepsy) whose relationship with typical rolandic epilepsy and among themselves
remains to be clarified
76.
Aicardi J. Epilepsy in Children. 2 ed. New York: Raven Press; 1994.
Ref ID: 224
77.
Ajuriaguerra Jd, Jaeggi A, Guignard F et al. The development and prognosis of dysphasia
in children. In: Morehead DM, Morehead AE, editors. Normal and Deficient Child
Language. Baltimore: University Park Press; 1976:345-385.
Ref ID: 1035
78.
Akbarian S, Sucher NJ, Bradley D et al. Selective alterations in gene expression for NMDA
receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 1996;16(1):19-30.
Ref ID: 2176
Abstract: NMDA receptor antagonists can induce a schizophrenia-like psychosis, but the
role of NMDA receptors in the pathophysiology of schizophrenia remains unclear.
Expression patterns of mRNAs for five NMDA receptor subunits (NR1/NR2A-D) were
determined by in situ hybridization in prefrontal, parieto-temporal, and cerebellar cortex of
brains from schizophrenics and from neuroleptic-treated and nonmedicated controls. In the
cerebral cortex of both schizophrenics and controls, mRNAs for NR1, NR2A, NR2B, and
NR2D subunits were preferentially expressed in layers II/III, Va, and VIa, with much higher
levels in the prefrontal than in the parieto-temporal cortex. Levels of mRNA for the NR2C
subunit were very low overall. By contrast, the cerebellar cortex of both schizophrenics and
controls contained very high levels of NR2C subunit mRNA, whereas levels for the other
subunit mRNAs were very low, except NR1, for which levels were moderate. Significant
alterations in the schizophrenic cohort were confined to the prefrontal cortex. Here there
was a shift in the relative proportions of mRNAs for the NR2 subunit family, with a 53%
relative increase in expression of the NR2D subunit mRNA. No comparable changes were
found in neuroleptic-treated or untreated controls. These findings indicate regional
heterogeneity of NMDA receptor subunit expression in human cerebral and cerebellar
cortex. In schizophrenics, the alterations in expression of NR2 subunit mRNA in prefrontal
17
cortex are potential indicators of deficits in NMDA receptor-mediated neurotransmission
accompanying functional hypoactivity of the frontal lobes
79.
Akbarian S, Kim JJ, Potkin SG, Hetrick WP, Bunney WEJ, Jones EG. Maldistribution of
interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. Arch
Gen Psychiat 1996;53(5):425-436.
Ref ID: 2183
Abstract: BACKGROUND: The cortical subplate is a transitory structure involved in the
formation of connections in developing cerebral cortex. Interstitial neurons, normally
present in subcortical white matter (WM) of the adult brain, have escaped the programmed
cell death that eliminates most subplate neurons. Previous investigations indicated a
maldistribution of one population of interstitial neurons in the WM of brains of schizophrenic
patients, suggesting a defect of the subplate during brain development. METHODS: Three
histochemically or immunocytochemically defined neuronal populations were studied in WM
beneath the middle frontal gyrus of 20 schizophrenic patients and 20 matched control
subjects. RESULTS: Brains of schizophrenic patients showed significant changes in the
distribution of the three neuronal populations: microtubule-associated protein 2 and
nonphosphorylated neurofilament-immunoreactive neurons showed a decreased density in
superficial WM and an increased density in deeper WM. Nicotinamide adenine dinucleotide
phosphate-diaphorase neurons were reduced in superficial WM and showed variable
densities in deeper WM. Thirty-five percent of the brains of schizophrenic patients but no
brains of the control subjects showed a maldistribution of neurons toward deeper WM with
at least two of the three markers. Changes in neuronal distribution were not linked to age,
gender, autolysis time, or subtype of schizophrenia. CONCLUSIONS: Selective
displacement of interstitial WM neurons in the frontal lobe of brains of schizophrenic
patients may indicate alteration in the migration of subplate neurons or in the pattern of
programmed cell death. Both could lead to defective cortical circuitry in the brains of
schizophrenic patients
80.
Akbarian S, Smith MA, Jones EG. Editing for an AMPA receptor subunit RNA in prefrontal
cortex and striatum in Alzheimer's disease, Huntington's disease and schizophrenia. Brain
Res 1995;699(2):297-304.
Ref ID: 2175
Abstract: Animal studies and cell culture experiments demonstrated that posttranscriptional
editing of the transcript of the GluR-2 gene, resulting in substitution of an arginine for
glutamine in the second transmembrane region (TM II) of the expressed protein, is
associated with a reduction in Ca2+ permeability of the receptor channel. Thus,
disturbances in GluR-2 RNA editing with alteration of intracellular Ca2+ homeostasis could
lead to neuronal dysfunction and even neuronal degeneration. The present study
determined the proportions of edited and unedited GluR-2 RNA in the prefrontal cortex of
brains from patients with Alzheimer's disease, in the striatum of brains from patients with
Huntington's disease, and in the same areas of brains from age-matched schizophrenics
and controls, by using reverse transcriptase-polymerase chain reaction, restriction
endonuclease digestion, gel electrophoresis and scintillation radiometry. In the prefrontal
cortex of controls, < 0.1% of all GluR-2 RNA molecules were unedited and > 99.9% were
edited; in the prefrontal cortex both of schizophrenics and of Alzheimer's patients
approximately 1.0% of all GluR-2 RNA molecules were unedited and 99% were edited. In
the striatum of controls and of schizophrenics, approximately 0.5% of GluR-2 RNA
molecules were unedited and 99.5% were edited; in the striatum of Huntington's patients
nearly 5.0% of GluR-2 RNA was unedited. In the prefrontal white matter of controls,
approximately 7.0% of GluR-2 RNA was unedited. In the normal human prefrontal cortex
and striatum, the large majority of GluR-2 RNA molecules contains a CGG codon for
arginine in the TMII coding region; this implies that the corresponding AMPA receptors
have a low Ca2+ permeability, as previously demonstrated for the rat brain. The process of
GluR-2 RNA editing is compromised in a region-specific manner in schizophrenia, in
Alzheimer's disease and Huntington's Chorea although in each of these disorders there is
18
still a large excess of edited GluR-2 RNA molecules. Disturbances of GluR-2 RNA editing
leading to excessive Ca2+ permeability, may contribute to neuronal dysfunction in
schizophrenia and to neuronal death in Alzheimer's disease and Huntington's disease
81.
Akbarian S, Kim JJ, Potkin SG et al. Gene expression for glutamic acid decarboxylase is
reduced without loss of neurons in prefrontal cortex of schizophrenics [see comments].
Arch Gen Psychiat 1995;52(4):258-266.
Ref ID: 2182
Abstract: BACKGROUND: Up-regulation of gamma-aminobutyric acidA (GABAA) receptors
and decreased GABA uptake in the cerebral cortex of schizophrenics suggest altered
GABAergic transmission, which could be caused by primary disturbance of GABA
synapses or by decreased production of the transmitter. Decreased production could be
due to a shutdown in GABA production or to loss of GABA neurons caused by cell death or
their failure to migrate to the cortex during brain development. METHODS: To discriminate
between these possibilities, we quantified levels of messenger RNA (mRNA) for the 67-kd
isoform of glutamic acid decarboxylase (GAD), the key enzyme in GABA synthesis, and the
number and laminar distribution of GAD mRNA--expressing neurons in the dorsolateral
prefrontal cortex (DLPFC) of schizophrenics and matched controls, using in situ
hybridization-histochemistry, densitometry, and cell-counting methods. These data were
compared with the total number of neurons, the number of small, round or ovoid neurons 8
to 15 microns in diameter, and overall frontal lobe volume. As a control, mRNA levels for
type II calcium-calmodulin-dependent protein kinase (CamIIK) were quantified. RESULTS:
Schizophrenics showed a pronounced decrease in GAD mRNA levels in neurons of layer I
(40%) and layer II (48%) and an overall 30% decrease in layers III to VI. There were also
strong overall reductions in GAD mRNA levels. The CamIIK mRNA levels showed no
significant differences between samples. No differences were found in the total number of
neurons nor in small, round or ovoid neurons, which should include a majority of the GABA
cells. Prefrontal gray and white matter volume did not differ significantly between controls
and schizophrenics. CONCLUSIONS: The prefrontal cortex of schizophrenics shows
reduced expression for GAD in the absence of significant cell loss. This may be brought
about by an activity-dependent down-regulation associated with the functional hypoactivity
of the DLPFC. The lack of significant alterations in cell numbers in the DLPFC and frontal
lobe volume in schizophrenics also implies that overall cortical neuronal migration had not
been compromised in development. Previous reports of altered neuronal distribution in the
subcortical white matter of schizophrenic brains in comparison with that of controls may
indicate disturbances of migration or programmed cell death in the cortical subplate,
leading to altered connection formation in the overlying cortex of schizophrenics and
activity-dependent down-regulation of neurotransmitter-related gene expression
82.
Akbarian S, Huntsman MM, Kim JJ et al. GABAA receptor subunit gene expression in
human prefrontal cortex: comparison of schizophrenics and controls. Cereb Cortex
1995;5(6):550-560.
Ref ID: 2185
Abstract: The prefrontal cortex of schizophrenics is hypoactive and displays changes
related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes
include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA
synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine
binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have
demonstrated that gene expression for GAD and for several GABAA receptor subunit
polypeptides is under control of neuronal activity, raising the possibility that similar
mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the
abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the
first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits
(alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns
were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ
hybridization histochemistry and densitometry. Three types of laminar expression pattern
19
were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the
predominant receptor subunits expressed in the mature cortex, were expressed at
comparatively high levels by cells of all six cortical layers, but most intensely by cells in
lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were
expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in
layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There
were no significant changes in overall mRNA levels for any of the receptor subunits in the
prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor
subunit mRNAs did not differ between schizophrenics and controls. Because gene
expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex
of schizophrenics, the previously reported upregulation of muscimol binding sites and
downregulation of benzodiazepine binding sites in the prefrontal and adjacent cingulate
cortex of schizophrenics are possibly due to posttranscriptional modifications of mRNAs
and their translated polypeptides
83.
Akefeldt A, Akefeldt B, Gillberg C. Voice, speech and language characteristics of children
with Prader-Willi syndrome. J Intel Disabil Res 1997;41(Pt 4):302-311.
Ref ID: 2808
Abstract: Eleven individuals with Prader-Willi syndrome (PWS), aged between 4 and 25
years, were compared with II non-PWS children of the same sex, age, body mass index
and IQ level. Voice, speech and language skills were generally impaired in subjects with
PWS. Oral motor function, pitch level and resonance were specifically disordered and
clearly differentiated the two groups from each other. Certain biological perinatal factors
separated subjects with PWS from other obese children and adolescents, but did not
differentiate within the group with PWS and could not account for the speech/language
problems. Underlying cerebral dysfunction, combined with a characteristic anatomy of the
mouth and larynx in PWS, contributes to altered voice, speech and language function
84.
Akefeldt A, Gillberg C. Hypomelanosis of Ito in three cases with autism and autistic- like
conditions. Dev Med Child Neurol 1991;33:737-743.
Ref ID: 1
85.
Akesson HO. The biological origin of mild mental retardation: a critical review. Acta
Psychiatr Scand 1986;74:3-7.
Ref ID: 3085
86.
Akil H, Brenner S, Kandel E et al. The future of psychiatric research: genomes and neural
circuits. Science 2010;327(5973):1580-1581.
Ref ID: 6634
87.
Akman CI. Nonconvulsive status epilepticus and continuous spike and slow wave of sleep
in children. Semin Pediatr Neurol 2010;17(3):155-162.
Ref ID: 6856
Abstract: Nonconvulsive status epilepticus (NCSE) is a special epileptic state that can be
more common than previously thought in children and adult patients. Currently, there is no
universally accepted definition for NCSE. Early and accurate diagnosis depends on a high
index of suspicion and rapid availability of electroencephalographic recording. The clinical
presentation of NCSE can vary from a mild confusional state to a coma. The underlying
etiology is also quite diverse. In critically ill patients, NCSE has been reported with
convulsive status epilepticus (CSE), hypoxemia, acute ischemic or hemorrhagic stroke,
encephalitis, or trauma. The estimated incidence of NCSE is 15% to 40% in post-CSE, 8%
in subarachnoid hemorrhage, and 8% to 10% in coma. As seen in CSE, there is a bimodal
distribution with NCSE in critically ill patients; children (age <1 year) and elderly appear to
be at great risk. NCSE has also been reported in a number of epilepsy syndromes, such as
childhood absence epilepsy, Panayiotopoulos syndrome, Lennox-Gastaut syndrome, and
Dravet syndrome. However, it is difficult to determine the incidence of NCSE in an
20
ambulatory setting because of the great variation in clinical presentation and underlying
etiology. This review examines the clinical features, outcome, and treatment approach for
NCSE in 2 different clinical settings, in ambulatory and critically ill patients. NCSE is
reviewed in children and adults to distinguish similarities and differences in their clinical
presentation
88.
Akshoomoff N, Farid N, Courchesne E, Haas R. Abnormalities on the neurological
examination and EEG in young children with pervasive developmental disorders. J Autism
Dev Disord 2007;37(5):887-893.
Ref ID: 5172
Abstract: This study examined the nature and frequency of neurological and EEG
abnormalities in 60 young children (ages 2-6 years) with pervasive developmental
disorders. A number of standard neurological functions could not be adequately assessed
due to the young age of the children and/or limited comprehension and cooperation. The
most common neurological deficits were hyporeflexia, stereotypies, and hypotonia. EEG
abnormalities were identified in 32% of the children while only two children were known to
have clinical seizures. The frequency of cases with hypotonia or hyporeflexia was more
common than in older children with this diagnosis. Results also indicate that EEG
abnormalities are common in this young population but clinical seizures are rare, confirming
other studies
89.
Akshoomoff N, Lord C, Lincoln AJ et al. Outcome classification of preschool children with
autism spectrum disorders using MRI brain measures. J Am Acad Child Adolesc Psychiatry
2004;43(3):349-357.
Ref ID: 4281
Abstract: OBJECTIVE: To test the hypothesis that a combination of magnetic resonance
imaging (MRI) brain measures obtained during early childhood distinguish children with
autism spectrum disorders (ASD) from typically developing children and is associated with
functional outcome. METHOD: Quantitative MRI technology was used to measure gray and
white matter volumes (cerebrum and cerebellum), total brain volume, and the area of the
cerebellar vermis in 52 boys with a provisional diagnosis of autism (aged 1.9-5.2 years) and
15 typically developing young children (aged 1.7-5.2 years). Diagnostic confirmation and
cognitive outcome data were obtained after the children reached 5 years of age.
RESULTS: A discriminant function analysis of the MRI brain measures correctly classified
95.8% of the ASD cases and 92.3% of the control cases. This set of variables also correctly
classified 85% of the ASD cases as lower functioning and 68% of the ASD cases as higher
functioning. CONCLUSIONS: These results indicate that variability in cerebellar and
cerebral size is correlated with diagnostic and functional outcome in very young children
with ASD
90.
Akshoomoff NA, Feroleto CC, Doyle RE, Stiles J. The impact of early unilateral brain injury
on perceptual organization and visual memory. Neuropsychologia 2002;40(5):539-561.
Ref ID: 7590
Abstract: Studies of young children with early unilateral brain injury have suggested that
while hemispheric differences in visuospatial processing appear to be present early in
development, the young brain is better able to compensate for injury than when the injury
occurs later, after networks have been established. The aim of this study was to determine
if this pattern continues later in development when these children are given a challenging
task: the Rey-Osterrieth Complex Figure. Experiment 1 included longitudinal data from ten
children with early left hemisphere (LH) injury and nine children with early right hemisphere
(RH) injury. Injury was presumed to be due to a prenatal or perinatal stroke. Compared with
typically developing children, both groups were poorer in copying the figure. With
development, these children produced reasonably accurate drawings but continued to use
the most immature and piecemeal strategy. In Experiment 2, copy and immediate memory
drawings from the 19 children with early unilateral brain injury were collected at a single
age (11-14 years). Eight of the ten children with LH injury organized their memory
21
reproductions around the core rectangle but included relatively few additional details. In
contrast, only two of the nine children with RH injury organized their memory reproductions
around the core rectangle and all but one produced the figure in a piecemeal manner. The
results from both studies demonstrate the continuation of subtle deficits in visuospatial
analysis with development but also the continued capacity for compensation
91.
Akshoomoff NA, Courchesne E, Townsend J. Attention coordination and anticipatory
control. Int Rev Neurobiol 1997;41:575-598.
Ref ID: 2921
Abstract: The coordination of the direction of selective attention is an adaptive function that
may be one of the many anticipatory tools under cerebellar control. This chapter presents
neurobehavioral, neurophysiological, and neuroimaging data to support our hypothesis that
the cerebellum plays a role in attentional functions. We discuss the idea that the cerebellum
is a master computational system that anticipates and adjusts responsiveness in a variety
of brain systems (e.g., sensory, attention, memory, language, affect) to efficiently achieve
goals determined by cerebral and other subcortical systems. [References: 80]
92.
Akshoomoff NA, Courchesne E. A new role of the cerebellum in cognitive operations.
Behav Neurosci 1992;106:157-168.
Ref ID: 117
93.
Alaghband-Rad J, McKenna K, Gordon CT et al. Childhood-onset schizophrenia: The
severity of premorbid course. J Am Acad Child Adolesc Psychiatry 1995;34(10):1273-1283.
Ref ID: 1469
94.
Alajouanine TH, Lhermitte F. Acquired aphasia in children. Brain 1965;88:653-662.
Ref ID: 702
95.
Alam SA, Robinson BK, Huang J, Green SH. Prosurvival and proapoptotic intracellular
signaling in rat spiral ganglion neurons in vivo after the loss of hair cells. J Comp Neurol
2007;503(6):832-852.
Ref ID: 6209
Abstract: Neurons depend on afferent input for survival. Rats were given daily kanamycin
injections from P8 to P16 to destroy hair cells, the sole afferent input to spiral ganglion
neurons (SGNs). Most SGNs die over an approximately 14-week period after
deafferentation. During this period, the SGN population is heterogeneous. At any given
time, some SGNs exhibit apoptotic markers--TUNEL and cytochrome c loss--whereas
others appear nonapoptotic. We asked whether differences among SGNs in intracellular
signaling relevant to apoptotic regulation could account for this heterogeneity. cAMP
response element binding protein (CREB) phosphorylation, which reflects neurotrophic
signaling, is reduced in many SGNs at P16, P23, and P32, when SGNs begin to die. In
particular, nearly all apoptotic SGNs exhibit reduced phospho-CREB, implying that
apoptosis is due to insufficient neurotrophic support. However, >32% of SGNs maintain
high phospho-CREB levels, implying access to neurotrophic support. By P60, when
approximately 50% of the SGNs have died, phospho-CREB levels in surviving neurons are
not reduced, and SGN death is no longer correlated with reduced phospho-CREB. Activity
in the proapoptotic Jun N-terminal kinase (JNK)-Jun signaling pathway is elevated in SGNs
during the cell death period. This too is heterogeneous: <42% of the SGNs exhibited high
phospho-Jun levels, but nearly all SGNs undergoing apoptosis exhibited elevated
phospho-Jun. Thus, heterogeneity among SGNs in prosurvival and proapoptotic signaling
is correlated with apoptosis. SGN death following deafferentation has an early phase in
which apoptosis is correlated with reduced phospho-CREB and a later phase in which it is
not. Proapoptotic JNK-Jun signaling is tightly correlated with SGN apoptosis
96.
Alant E. The use of Bliss symbols as a first step into literacy with four children with Down
syndrome. South African Journal of Communication Disorders - die Suid-Afrikaanse
22
Tydskrif vir Kommunikasieafwykings 1994;41:23-31.
Ref ID: 3045
Abstract: This study describes the use of Bliss symbolics as a first step into literacy with
four children with Down syndrome in a preschool setting. Initial stages of the intervention
programme are discussed as well as the children's ability to read Bliss symbols six months
after commencement of the programme. Symbol errors are analyzed and implications for
further research discussed
97.
Alarcon M, Cantor RM, Liu J, Gilliam TC, Geschwind DH. Evidence for a language
quantitative trait locus on chromosome 7q in multiplex autism families. Am J Hum Genet
2002;70(1):60-71.
Ref ID: 4501
Abstract: Autism is a syndrome characterized by deficits in language and social skills and
by repetitive behaviors. We hypothesized that potential quantitative trait loci (QTLs) related
to component autism endophenotypes might underlie putative or significant regions of
autism linkage. We performed nonparametric multipoint linkage analyses, in 152 families
from the Autism Genetic Resource Exchange, focusing on three traits derived from the
Autism Diagnostic Interview: "age at first word," "age at first phrase," and a composite
measure of "repetitive and stereotyped behavior." Families were genotyped for 335
markers, and multipoint sib pair linkage analyses were conducted. Using nonparametric
multipoint linkage analysis, we found the strongest QTL evidence for age at first word on
chromosome 7q (nonparametric test statistic [Z] 2.98; P=.001), and subsequent linkage
analyses of additional markers and association analyses in the same region supported the
initial result (Z=2.85, P=.002; chi(2)=18.84, df 8, P=.016). Moreover, the peak fine-mapping
result for repetitive behavior (Z=2.48; P=.007) localized to a region overlapping this
language QTL. The putative autism-susceptibility locus on chromosome 7 may be the result
of separate QTLs for the language and repetitive or stereotyped behavior deficits that are
associated with the disorder
98.
Alberti PW. Hearing conservation. In: Alberti PW, Ruben RJ, editors. Otologic medicine and
surgery, Vol. 2. New York: Churchill Livingstone; 1988:1739-1752.
Ref ID: 460
99.
Alberti PW, Ruben RJ. Otologic medicine and surgery. 1 ed. New York, NY: Churchill
Livingstone; 1988.
Ref ID: 6303
100. Alberti PW. Noise and the ear. In: Ballantyne J, Groves J, editors. Scott-Brown's Diseases
of the Ear, Nose and Throat. 4th edition. The Ear, Vol. 2. London: Butterworths; 1979.
Ref ID: 766
101. Albright AL. Neurosurgical treatment of spasticity and other pediatric movement disorders.
J Child Neurol 2003;18 Suppl 1:S67-S78.
Ref ID: 3864
Abstract: For children whose spasticity and movement disorders are inadequately treated
by oral medications and botulinum toxins, neurosurgical procedures are now available to
effectively treat spasticity, tremor, and many cases of dystonia. Spastic diplegia can be
treated with selective lumbar rhizotomies, which significantly decrease spasticity, increase
range of motion, and improve Gross Motor Function Measure scores. Children with spastic
quadriparesis and those with secondary dystonia can be treated with intrathecal baclofen,
which diminishes both spasticity and dystonia and is associated with improved function and
quality of life. Children with primary dystonia and those with tremor can be treated with
deep brain stimulation of the internal globus pallidus and thalamus, respectively. Some
children with chorea respond to deep brain stimulation. There are no effective
neurosurgical treatments for athetosis or ataxia. The effectiveness of neurosurgical
treatments of pediatric movement disorders has increased significantly in the past 15 years
23
102. Albright AL, Gilmartin R, Swift D, Krach LE, Ivanhoe CB, McLaughlin JF. Long-term
intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg
2003;98(2):291-295.
Ref ID: 3874
Abstract: OBJECT: The goal of this study was to ascertain the long-term effectiveness and
safety of intrathecal baclofen (ITB) in the treatment of spasticity of cerebral origin in
children and young adults. METHODS: A prospective, multicenter study was conducted in
68 patients who had been enrolled in the initial evaluation of ITB therapy and were willing to
participate in long-term surveillance. Seventy-three percent of the patients were younger
than 16 years of age at the time of study entry. The patients were examined at least every
3 months and were observed for an average of 70 months. At each follow-up visit,
spasticity in the upper and lower extremities was evaluated by applying Ashworth scores.
All adverse events and complications were recorded on standardized data forms. Spasticity
in both upper and lower extremities decreased significantly (p < 0.005) and remained
decreased up to 10 years. The dosage of ITB increased from a mean of 157 microg/day 3
months after pump insertion to 300 microg/day at 2 years postimplantation, and remained
relatively stable thereafter. There were no significant differences in ITB dosage in children
of different ages. Adverse events potentially related to ITB therapy occurred in 50% of
patients within 2 months after pump insertion and in 50% of patients thereafter; hypotonia
and lethargy were the two most common adverse events. The most common complications
of surgery were catheter-related problems (31%), seromas (24%), and cerebrospinal fluid
leaks (15%). CONCLUSIONS: Intrathecal baclofen provides effective long-term treatment
of spasticity of cerebral origin and its effects do not appear to diminish with time. This
therapy is frequently associated with adverse side effects that usually can be alleviated by
adjustments in dosage
103. Alcantara JI, Weisblatt EJ, Moore BC, Bolton PF. Speech-in-noise perception in
high-functioning individuals with autism or Asperger's syndrome. J Child Psychol Psychiatry
2004;45(6):1107-1114.
Ref ID: 4794
Abstract: BACKGROUND: High-functioning individuals with autism (HFA) or Asperger's
syndrome (AS) commonly report difficulties understanding speech in situations where there
is background speech or noise. The objective of this study was threefold: (1) to verify the
validity of these reports; (2) to quantify the difficulties experienced; and (3) to propose
possible mechanisms to explain the perceptual deficits described. METHOD:
Speech-in-noise perception abilities were measured using speech reception thresholds
(SRTs), defined as the speech-to-noise ratio (SNR) at which approximately 50% of the
speech is correctly identified. SRTs were measured for 11 individuals with HFA/AS and 9
age/IQ-matched normal-hearing control subjects, using an adaptive procedure, in a
non-reverberant sound-attenuating chamber. The speech materials were standardised lists
of everyday sentences spoken by a British male speaker. The background sounds were:
(1) a single female talker; (2) a steady speech-shaped noise; (3) a speech-shaped noise
with temporal dips; (4) a steady speech-shaped noise with regularly spaced spectral dips;
and (5) a speech-shaped noise with temporal and spectral dips. RESULTS: SRTs for the
HFA/AS group were generally higher (worse) than those for the controls, across the five
background sounds. A statistically significant difference in SRTs between the subject
groups was found only for those background sounds that contained temporal or
spectro-temporal dips. SRTs for the HFA/AS individuals were 2 to 3.5 dB higher than for
the controls, equivalent to a substantial decrease in speech recognition. Expressed another
way, the HFA/AS individuals required a higher SNR, whenever there were temporal dips in
the background sound, to perform at the same level as the controls. CONCLUSIONS: The
results suggest that the speech-in-noise perception difficulties experienced by individuals
with autism may be due, in part, to a reduced ability to integrate information from glimpses
present in the temporal dips in the noise
24
104. Alexander AL, Lee JE, Lazar M et al. Diffusion tensor imaging of the corpus callosum in
Autism. NeuroImage 2007;34(1):61-73.
Ref ID: 5148
Abstract: The corpus callosum is the largest commissural white matter pathway that
connects the hemispheres of the human brain. In this study, diffusion tensor imaging (DTI)
was performed on subject groups with high-functioning autism and controls matched for
age, handedness, IQ, and head size. DTI and volumetric measurements of the total corpus
callosum and subregions (genu, body and splenium) were made and compared between
groups. The results showed that there were significant differences in volume, fractional
anisotropy, mean diffusivity, and radial diffusivity between groups. These group differences
appeared to be driven by a subgroup of the autism group that had small corpus callosum
volumes, high mean diffusivity, low anisotropy, and increased radial diffusivity. This
subgroup had significantly lower performance IQ measures than either the other individuals
with autism or the control subjects. Measurements of radial diffusivity also appeared to be
correlated with processing speed measured during the performance IQ tests. The subgroup
of autism subjects with high mean diffusivity and low fractional anisotropy appeared to
cluster with the highest radial diffusivities and slowest processing speeds. These results
suggest that the microstructure of the corpus callosum is affected in autism, which may be
related to nonverbal cognitive performance
105. Alexander AW, Slinger-Constant AM. Current status of treatments for dyslexia: critical
review. J Child Neurol 2004;19(10):744-758.
Ref ID: 7397
Abstract: The acquisition of reading is a complex neurobiologic process. Identifying the
most effective instruction and remedial intervention methods for children at risk of
developing reading problems and for those who are already struggling is equally complex.
This article aims to provide the clinician with a review of more current findings on the
prevention and remediation of reading problems in children, along with an approach to
considering the diagnosis and treatment of a child with dyslexia. The first part of the review
describes interventions targeted at preventing reading difficulties in the at-risk younger
child. The second part of the review discusses the efficacy of approaches to treat the older,
reading-disabled child ("intervention studies"). Factors that impact the response to
treatment are also discussed, as are neuroimaging studies that offer insight into how the
brain responds to treatment interventions. With appropriate instruction, at-risk readers can
become both accurate and fluent readers. In contrast, although intensive, evidence-based
remedial interventions can markedly improve reading accuracy in older, reading-disabled
children, they have been significantly less effective in closing the fluency gap. Owing to the
dynamic course of language development and the changes in language demands over
time, even after a child has demonstrated a substantial response to treatment interventions,
his or her subsequent progress should be carefully tracked to ensure optimal progress
toward the development of functional reading and written language skills
106. Alexander MP, Stuss DT, Picton T, Shallice T, Gillingham S. Regional frontal injuries cause
distinct impairments in cognitive control. Neurology 2007;68(18):1515-1523.
Ref ID: 5019
Abstract: BACKGROUND: Lesions of the frontal lobes may impair the capacity of patients
to control otherwise intact cognitive operations in the face of ambiguous sensory input or
conflicting possible responses. OBJECTIVE: To address the question of whether focal
lesions in different regions of the frontal lobes produced specific impairments in cognitive
control. METHODS: We evaluated 42 patients with chronic frontal lesions and 38 control
subjects on a modified Stroop test that allowed measurement of reaction times and errors.
Planned, stratified analyses permitted identification of discrete frontal lesions that are
critical for impaired performance. RESULTS: Lesions of the left ventrolateral region
produced an increased number of incorrect responses to distractors. Lesions of a large
portion of the right superior medial region, including anterior cingulate, supplementary
motor area (SMA), pre-SMA, and dorsolateral areas, caused a slow reaction time and a
25
decreased number of correct responses to targets. CONCLUSION: Lesions in two distinct
frontal regions impair cognitive control for a Stroop task, and the mechanisms of
impairment are specific to the region of injury. This is support for a general proposal that
the supervisory system is constructed of distinct subsystems
107. Alexander MP. Impairments of procedures for implementing complex language are due to
disruption of frontal attention processes. J Int Neuropsychol Soc 2006;12(2):236-247.
Ref ID: 5020
Abstract: Production of complex discourse-lengthy, open-ended utterances and
narratives-requires intact basic language operations, but it also requires a series of learned
procedures for construction of complex, goal-directed communications. The progression of
clinical disorders from transcortical motor aphasia to dynamic aphasia to discourse
impairments represents a progression of procedural deficits from basic morpho-syntax to
complex grammatical structures to narrative and a progression of lesions from posterior
frontal to polar and/or lateral frontal to medial frontal. Two cases of impaired utilization of
language exemplify the range of impairments from clearly aphasic agrammatic, nonfluency
to less and less "aphasic" and more and more executive impairments from transcortical
motor aphasia to dynamic aphasia to narrative discourse disorder. The clinical
phenomenology of these disorders gradually comes to be more accurately defined in the
terminology of executive deficits than that of aphasia. The executive deficits are, in turn,
based on impairments in various components of attention. Specific impairments in
energizing attention and setting response criteria associated, respectively, with lesions in
superior medial and left ventrolateral frontal regions may cause defective recruitment of the
procedures of complex language assembly
108. Alexander MP, Stuss DT, Shallice T, Picton TW, Gillingham S. Impaired concentration due
to frontal lobe damage from two distinct lesion sites. Neurology 2005;65(4):572-579.
Ref ID: 4607
Abstract: BACKGROUND: Investigations of cognitive deficits after frontal lobe damage
have commonly relied on multidimensional tests and relatively coarse specification of lesion
anatomy. Some form of impairment in attention is often asserted to cause the revealed
deficits. OBJECTIVE: To describe a disorder of attention in patients with frontal damage
using a theoretical model of the fundamental cognitive processes that underlie attention.
METHODS: The ability to perform a task of concentrated responding was studied in 43
patients with well-defined chronic frontal lesions and 38 control subjects using a continuous
reaction time (RT) test. Performance measures were mean RT, RT across blocks of the
test, and errors. Lesion measures were coarse localization and a hot-spot analysis to
detect finer grained lesion effects. RESULTS: Only patients with lesions in the right
superomedial (SM) frontal regions had significantly prolonged RT consistently across the
entire test. The critical lesion was in Brodmann's areas 24, 32, 9, and 46 days and in the
adjacent corpus callosum. Patients with lesions in left lateral frontal (LL) regions made
significantly more errors on the 20% of trials in the first block. The critical lesion was in
areas 44, 45, and 47/12. CONCLUSION: Concentrating attention to respond is affected by
lesions in two different frontal regions for reasons that reflect impairments in different
cognitive processes. Right superomedial lesions cause an insufficient energizing of
attention to respond. Left lateral lesions cause defective setting of specific
stimulus-response contingencies. Constrained tests of attention can demonstrate
impairments in specific cognitive operations following lesions to different regions of the
frontal lobes
109. Alford RL, Friedman TB, Keats BJ et al. Early childhood hearing loss: clinical and molecular
genetics. An educational slide set of the American College of Medical Genetics. Genet Med
2003;5(4):338-341.
Ref ID: 6373
Abstract: An educational slide set entitled "Early Childhood Hearing Loss: Clinical and
Molecular Genetics" is offered by the American College of Medical Genetics (ACMG). The
26
slide set is produced in Microsoft PowerPoint 2002. It is extensively illustrated and
supported with teaching tools, explanations of each slide and figure, links to Internet
resources, and a bibliography. The slide set is expected to be used as a resource for
self-directed learning and in support of medical genetics teaching activities. The slide set is
available through the ACMG (http://www.acmg.net) for $20, plus applicable tax and
shipping. It is the first in a series of educational slide sets to be developed by the ACMG
110. Ali ZS, Van Der Voorn JP, Powers JM. A comparative morphologic analysis of adult onset
leukodystrophy with neuroaxonal spheroids and pigmented glia--a role for oxidative
damage. J Neuropathol Exp Neurol 2007;66(7):660-672.
Ref ID: 6681
Abstract: We performed a blinded study on 5 cases of hereditary diffuse
leukoencephalopathy with spheroids and 10 cases of the pigmentary type of
orthochromatic leukodystrophy, 6 of the latter having a family history of neurologic illness.
Patients presented in the third to sixth decade with behavioral, cognitive, and motor
symptoms. All cases displayed widespread myelin loss, predominantly frontotemporal with
relative sparing of subcortical U-fibers, and variable numbers of both neuroaxonal
spheroids and pigmented glia. Immunohistochemically, spheroids contained amyloid
precursor/neurofilament proteins, several neurotransmitters or neuropeptides, and
ubiquitin. Cytoplasmic inclusions in glia and numerous pigmented macrophages were
autofluorescent and stained consistently with diastase-periodic acid-Schiff, prolonged
Ziehl-Nielsen, and Sudan black, but the same cells labeled inconsistently for iron or ferritin.
Ultrastructurally, the most characteristic autofluorescent glial lipopigments consisted of
bosselated masses of granular, electron-dense material. These morphologic features are
those of ceroid, an end-product of oxidative damage. Glial immunoreactivity for markers of
oxidative stress (hemeoxygenase-1 and superoxide dismutase 2) and damage
(4-hydroxynonenal, malondialdehyde, and nitrotyrosine) was noted, particularly in cases
with increased iron and ferritin. These data support the hypothesis that the similar
clinicopathologic features of hereditary diffuse leukoencephalopathy with spheroids and the
pigmentary type of orthochromatic leukodystrophy reflect a common disease due, at least
in part, to an oxidative insult
111. Allan WC, Vohr B, Makuch RW, Katz KH, Ment LR. Antecedents of cerebral palsy in a
multicenter trial of indomethacin for intraventricular hemorrhage [see comments]. Archives
of Pediatrics & Adolescent Medicine 1997;151(6):580-585.
Ref ID: 2000
Abstract: OBJECTIVES: To determine if cerebral palsy (CP) rates were lower in the active
treatment group compared with the control group, as improved survival rates of very
low-birth-weight infants are postulated to be the cause of the increased incidence of CP in
preterm infants, to evaluate relationships between multiple prenatal, perinatal, and
postnatal variables and CP to understand better its antecedents in very low-birth-weight
infants in the era of surfactant replacement therapy, and to determine the usefulness of a
cranial ultrasonographic (US) scan in predicting CP. DESIGN: Inception cohort follow-up
study as part of a randomized controlled trial of low-dose indomethacin sodium for the
prevention of intraventricular hemorrhage. SETTING: Neonatal intensive care units at 3
medical centers. PATIENTS: Infants with birth weights between 600 and 1250 g were
eligible, and 505 infants were enrolled in the original study. Of these infants, 440 (87%)
survived; neurologic examinations were completed on 381 infants (86%) at 36 months
corrected age. MAIN OUTCOME MEASURES: Statistical analyses were performed to
identify the antecedents of CP, including the results of frequent cranial US scans obtained
throughout the newborn period. RESULTS: Cerebral palsy was found in 36 (9.5%) of 381
infants at 36 months corrected age (range, 33-39 months corrected age). Univariate
analysis identified chorioamnionitis, treatment with surfactant, bronchopulmonary dysplasia,
and abnormal cranial US findings as antecedents of CP. Periventricular leukomalacia and
ventriculomegaly were associated with the highest detection rates for CP (37% and 30%,
respectively) with acceptable false-positive rates. Multivariate analysis identified
27
bronchopulmonary dysplasia and an abnormal cranial US scan showing grade 3 to 4
intraventricular hemorrhage, periventricular leukomalacia, or ventriculomegaly as
independent predictors of CP. Odds ratios for the detection of CP using cranial US findings
tabulated by hospital day were in the range of 7 to 26 beginning on day 2. CONCLUSION:
The results suggest that cranial US findings are useful predictors of CP during a patient's
stay in the hospital
112. Allardyce J, Gaebel W, Zielasek J, van OJ. Deconstructing Psychosis conference February
2006: the validity of schizophrenia and alternative approaches to the classification of
psychosis. Schizophr Bull 2007;33(4):863-867.
Ref ID: 7049
Abstract: The DSM V planning process is currently underway and it has once again ignited
the debate about the validity of the schizophrenia diagnosis. In this paper, we review the
psychometric literature examining the evidence for discontinuity between schizophrenia
and normality and the distinction between schizophrenia and other psychotic disorders. We
conclude by proposing potential alternative approaches to refining the classification of
psychosis
113. Allen DA, Steinberg M, Dunn M et al. Autistic disorder versus other pervasive
developmental disorders in young children: Same or different? Eur Child Adoles Psychiatry
2001;10:67-78.
Ref ID: 113
Abstract: Eighteen preschool children diagnosed according to the Diagnostic and Statistical
Manual of Mental Disorders Third Edition Revised (DSM III-R) as having Pervasive
Developmental Disorder-Not Otherwise Specified (PDD-NOS) were compared to 176
children with DSM III-R Autistic Disorder (AD), and to 311 non-autistic children with
developmental language disorders (DLD) (N = 201) or low IQ (N = 110). All children were
partitioned into "high" and "low" cognitive subgroups at a nonverbal IQ of 80. Within
cognitive subgroups, the 18 PDD-NOS children did not differ significantly from either the
DLD or the AD children in verbal and adaptive skills and obtained scores intermediate
between those of these groups. The PDD-NOS did not differ from the AD children in
maladaptive behaviors. Both the PDD-NOS and AD children had many more of these
behaviors than the non-autistic comparison groups. Children in the "high" and "low"
cognitive subgroups of AD, but not of PDD-NOS, differed substantially on most measures,
with the children with lower cognitive scores significantly more impaired on all measures.
Similarity of PDD-NOS children to AD children in maladaptive behaviors and an
intermediate position between autistic and non-autistic groups on virtually all measures
explains the difficulty clinicians encounter in classifying children with PDD and raises
questions about the specificity of these diagnostic subtypes of the autistic spectrum.
114. Allen DA, Mendelson L. Parent, child, and professional: meeting the needs of young autistic
children and their families in a multidisciplinary therapeutic nursery model. In: Epstein S,
editor. Autistic spectrum disorders and psychoanalytic ideas: Reassessing the fit. Hillsdale,
NJ: The Analytic Press; 2000:704-731.
Ref ID: 3279
115. Allen DA. Tratamiento educativo para ninos autistas preescolares. In: Fejerman N, Arroyo
HA, Massaro ME, Riggieri VL, editors. Autismo Infantil Y Otros Trastornos del Desarrollo.
Buenos Aires: Paidos; 1994:109-121.
Ref ID: 307
116. Allen DA, Rapin I. Autistic children are also dysphasic. In: Naruse H, Ornitz E, editors.
Neurobiology of Infantile Autism. Amsterdam NL: Excerpta Medica; 1992:73-80.
Ref ID: 385
28
117. Allen DA. Variability in the clinical presentation of autism: issues of diagnosis and treatment
in the preschool years. In: Amir N, Rapin I, Branski D, editors. 1 ed. Basel, Switzerland:
Karger; 1991:36-49.
Ref ID: 4608
118. Allen DA, Mendelson L, Rapin I. Syndrome specific remediation in preschool
developmental dysphasia. In: French JH, Harel S, Casaer P, Gottlieb MI, Rapin I, De Vivo
DC, editors. Child Neurology and Developmental Disabilities. Baltimore: Paul Brookes;
1989:233-243.
Ref ID: 351
119. Allen DA. Developmental language disorders in preschool children: Clinical subtypes and
syndromes. School Psychol Rev 1989;18:442-451.
Ref ID: 893
120. Allen DA. Autistic spectrum disorders: Clinical presentation in preschool children. J Child
Neurol 1988;3:s48-s56.
Ref ID: 384
121. Allen DA, Rapin I, Wiznitzer M. Communication disorders of preschool children: The
physician's responsibility. Journal of Developmental and Behavioral Pediatrics
1988;9:164-170.
Ref ID: 682
122. Allen DA, Rapin I. Language disorders in preschool children: Predictors of outcome. A
preliminary report. Brain Dev 1980;2:73-80.
Ref ID: 897
123. Allen G, Muller RA, Courchesne E. Cerebellar function in autism: functional magnetic
resonance image activation during a simple motor task. Biol Psychiatry
2004;56(4):269-278.
Ref ID: 4557
Abstract: BACKGROUND: The cerebellum is one of the most consistent sites of
neuroanatomic abnormality in autism, yet it is still unclear how such pathology impacts
cerebellar function. In normal subjects, we previously demonstrated with functional
magnetic resonance imaging (fMRI) a dissociation between cerebellar regions involved in
attention and those involved in a simple motor task, with motor activation localized to the
anterior cerebellum ipsilateral to the moving hand. The purpose of the present investigation
was to examine activation in the cerebella of autistic patients and normal control subjects
performing this motor task. METHODS: We studied eight autistic patients and eight
matched normal subjects, using fMRI. An anatomic region-of-interest approach was used,
allowing a detailed examination of cerebellar function. RESULTS: Autistic individuals
showed significantly increased motor activation in the ipsilateral anterior cerebellar
hemisphere relative to normal subjects, in addition to atypical activation in contralateral and
posterior cerebellar regions. Moreover, increased activation was correlated with the degree
of cerebellar structural abnormality. CONCLUSIONS: These findings strongly suggest
dysfunction of the autistic cerebellum that is a reflection of cerebellar anatomic abnormality.
This neurofunctional deficit might be a key contributor to the development of certain
diagnostic features of autism (e.g., impaired communication and social interaction,
restricted interests, and stereotyped behaviors)
124. Allen G, Courchesne E. Attention function and dysfunction in autism. Front Biosci
2001;6:D105-D119.
Ref ID: 3443
Abstract: Impairments of attention are among the most consistently reported cognitive
deficits in autism, and they continue to be a key focus of research. This is in no doubt due
29
to the importance of normal attention function to the development of many so-called "higher
level" cognitive operations, and to the likely involvement of attention dysfunction in certain
clinical features of autism. Autistic individuals display a wide range of attentional abilities
and deficits across the many domains of attention function, including selective, sustained,
spatial, and shifting attention operations. This unique pattern of attention function and
dysfunction has profound implications for the development and treatment of autistic
children. The present review will explore this pattern of attentional strengths and
weaknesses and the neural defects that underlie them
125. Allen G, Buxton RB, Wong EC, Courchesne E. Attentional activation of the cerebellum
independent of motor involvement. Science 1997;275(5308):1940-1943.
Ref ID: 2425
Abstract: The cerebellum traditionally has been viewed as a neural device dedicated to
motor control. Although recent evidence shows that it is involved in nonmotor operations as
well, an important question is whether this involvement is independent of motor control and
motor guidance. Functional magnetic resonance imaging was used to demonstrate that
attention and motor performance independently activate distinct cerebellar regions. These
findings support a broader concept of cerebellar function, in which the cerebellum is
involved in diverse cognitive and noncognitive neurobehavioral systems, including the
attention and motor systems, in order to anticipate imminent information acquisition,
analysis, or action
126. Allen JB. Cochlear signal processing. In: Jahn AF, Santos-Sacchi J, editors. Physiology of
the ear. New York: Raven Press; 1988:243.
Ref ID: 4045
127. Allen SM, Rice SN. Risperidone antagonism of self-mutilation in a Lesch-Nyhan patient.
Progr Neuro-Psychopharmacol & Biol Psychiat 1996;20(5):793-800.
Ref ID: 1991
128. Allman J, Hakeem A, Watson K. Two phylogenetic specializations in the human brain.
Neuroscientist 2002;8(4):335-346.
Ref ID: 5210
Abstract: In this study, two anatomical specializations of the brain in apes and humans are
considered. One of these is a whole cortical area located in the frontal polar cortex
(Brodmann's area 10), and the other is a morphologically distinctive cell type, the spindle
neuron of the anterior cingulate cortex. The authors suggest that the spindle cells may relay
to other parts of the brain--especially to area 10, the outcome of processing within the
anterior cingulate cortex. This relay conveys the motivation to act. It particularly concerns
the recognition of having committed an error that leads to the initiation of adaptive
responses to these adverse events so as to reduce error commission. This capacity is
related to the development of self-control as an individual matures and gains social insight.
Although the anterior cingulate deals with the individual's immediate response to changing
conditions, area 10 is involved in the retrieval of memories from the individual's past
experience and the capacity to plan adaptive responses. The authors suggest that these
neurobehavioral specializations are crucial aspects of intelligence as defined as the
capacity to make adaptive responses to changing conditions. The authors further
hypothesize that these specializations facilitated the evolution of the unique capacity for the
intergenerational transfer of the food and information characteristic of human extended
families
129. Allman TM. Patterns of spelling in young deaf and hard of hearing students. Am Ann Deaf
2002;147(1):46-64.
Ref ID: 4168
Abstract: The study examined the invented spelling abilities demonstrated by kindergarten
and first-grade deaf and hard of hearing students. The study included two parts: In Part 1,
30
the researcher compared three groups (deaf, hard of hearing, and hearing) using
posttesting only on the Early Reading Screening Inventory, or ERSI (Morris, 1998), and in
part 2 collected and analyzed samples of the spelling of deaf students in a Total
Communication program. Analysis showed that the deaf group performed significantly
differently in three areas: concept of word, word recognition, and phoneme awareness
("invented spelling"; Read, 1971). The deaf group outperformed the hearing and hard of
hearing groups in concept of word and word recognition. But in phoneme awareness, the
deaf group performed significantly less well than the hearing group. Therefore, the deaf
group's spelling was followed for 1 year. Deaf students' spelling patterns were not the same
as those of hearing and hard of hearing students. Deaf students' spelling miscues were
directly related to the cueing systems of lipreading, signing, and fingerspelling
130. Alsdorf R, Wyszynski DF. Teratogenicity of sodium valproate. Expert Opin Drug Saf
2005;4(2):345-353.
Ref ID: 5574
Abstract: The teratogenicity of the widely popular antiepileptic drug (AED) and mood
stabiliser sodium valproate (also known as valproate, VPA) has been evidenced by
previous research; however, these findings have often been limited by a small population
sample of exposed women and a retrospective study design. Many factors contribute to the
teratogenicity of VPA. These include the number of drugs that are co-administered, drug
dosage, differences in maternal and/or infant metabolism, the gestational age of the fetus
at exposure, and hereditary susceptibility. VPA has been associated with a variety of major
and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and
palate, cardiovascular abnormalities, genitourinary defects, developmental delay,
endocrinological disorders, limb defects, and autism. It has been suggested that
polytherapy treatment in epileptic pregnant women increases the risk of teratogenicity in
offspring. Furthermore, there is an established relationship between VPA dose and adverse
outcome. Large single doses of VPA potentially cause high peak levels in the fetal serum
resulting in deleterious effects. Currently there is an increase in the number of national and
international pregnancy registries being formed in an effort to better identify the teratogenic
effects of AEDs. These efforts hope to enhance our understanding of AEDs and their
associated risks by addressing past study limitations
131. Alsobrook JP, Pauls DL. The genetics of Tourette syndrome. Neurology Clinics
1997;15(2):381-393.
Ref ID: 2391
Abstract: Tourette syndrome has significant genetic determinants. The mode of
transmission, while mildly controversial, generally is thought to be due to a single major
locus inherited either as an autosomal dominant trait with reduced penetrance, or as a trait
with intermediate inheritance in which some heterozygotes manifest the disorder. These is
evidence for a Tourette syndrome spectrum of symptoms that includes
obsessive-compulsive disorder. Systematic genome linkage studies of Tourette syndrome
are progressing, but to date there are no significant linkage findings, although the search
has included many neurologically relevant candidate genes. [References: 83]
132. Altamura C, Dell'Acqua ML, Moessner R, Murphy DL, Lesch KP, Persico AM. Altered
neocortical cell density and layer thickness in serotonin transporter knockout mice: a
quantitation study. Cereb Cortex 2007;17(6):1394-1401.
Ref ID: 5164
Abstract: The neurotransmitter serotonin (5-HT) plays morphogenetic roles during
development, and their alteration could contribute to autism pathogenesis in humans. To
further characterize 5-HT's contributions to neocortical development, we assessed the
thickness and neuronal cell density of various cerebral cortical areas in serotonin
transporter (5-HTT) knockout (ko) mice, characterized by elevated extracellular 5-HT
levels. The thickness of layer IV is decreased in 5-HTT ko mice compared with wild-type
(wt) mice. The overall effect on cortical thickness, however, depends on the genetic
31
background of the mice. Overall cortical thickness is decreased in many cortical areas of
5-HTT ko mice with a mixed c129-CD1-C57BL/6J background. Instead, 5-HTT ko mice
backcrossed into the C57BL/6J background display increases in supragranular and
infragranular layers, which compensate entirely for decreased layer IV thickness, resulting
in unchanged or even enhanced cortical thickness. Moreover, significant increases in
neuronal cell density are found in 5-HTT ko mice with a C57BL/6J background (wt:hz:ko
ratio = 1.00:1.04:1.17) but not in the mixed c129-CD1-C57BL/6J 5-HTT ko animals. These
results provide evidence of 5-HTT gene effects on neocortical morphology in epistatic
interaction with genetic variants at other loci and may model the effect of functional 5-HTT
gene variants on neocortical development in autism
133. Alvarez Retuerto AI, Cantor RM, Gleeson JG et al. Association of common variants in the
Joubert syndrome gene (AHI1) with autism. Hum Mol Genet 2008;17:3887-3896.
Ref ID: 5821
Abstract: It has been suggested, that autism, like other complex genetic disorders, may
benefit from the study of rare or Mendelian variants associated with syndromic or
non-syndromic forms of the disease. However, there are few examples in which common
variation in genes causing a Mendelian neuropsychiatric disorder, have been shown to
contribute to disease susceptibility in an allied common condition. Joubert syndrome is a
rare recessively inherited disorder with mutations reported at several loci including the gene
Abelson's Helper Integration 1 (AHI1). A significant proportion of patients with Joubert
syndrome, in some studies up to 40%, have been diagnosed with autism spectrum disorder
(ASD) and several linkage studies in ASD have nominally implicated the region on 6q
where AHI1 resides. To evaluate AHI1 in ASD, we performed a 3-stage analysis of AHI1 as
an a priori candidate gene for autism. Re-sequencing was first used to screen AHI1,
followed by 2 subsequent association studies, one limited, and one covering the gene more
completely, in Autism Genetic Resource Exchange (AGRE) families. In stage 3, we found
evidence of an associated haplotype in AHI1 with ASD after correction for multiple
comparisons, in a region of the gene that had been previously associated with
schizophrenia. These data suggest a role for AHI1 in common disorders affecting human
cognition and behavior
134. Alves FR, Ribeiro FA. Clinical data and hearing of individuals with Alport syndrome. Braz J
Otorhinolaryngol 2008;74(6):807-814.
Ref ID: 6389
Abstract: Alport Syndrome (AS) is a hereditary disease, characterized by nephropathy,
often times with sensorineural hearing loss and ocular defects. AIM: to analyze the clinical
and hearing information from individuals with AS, more specifically the correlation between
renal disorder and hearing loss (HL). STUDY DESIGN: clinical prospective with
cross-sectional cohort. MATERIALS AND METHODS: 37 individuals underwent
otorhinolaryngological evaluation and were submitted to audiologic tests. For HL statistical
analysis we considered only the results from the pure tone audiometries. RESULTS: of the
28 individuals with clinical alterations, we found 46.4% of DLX and 53.6% of AD. HL
happened to 46.1% of the individuals evaluated. 12 patients presented HL in the
audiometric test: 11.5% mild and 34.6% moderate. Comparing the normal relatives with
those with renal disorder; all that had HL also had renal disorder. In 30.8% the curve shape
was mild descending in the high frequencies and in 11.5% it was flat. CONCLUSIONS: The
inheritance pattern distribution does not match literature descriptions. HL is a frequent
extra-renal finding. There is an association between renal involvement and HL (p= 0.009).
The most frequent curve shapes: mild descending in the high frequencies and flat. There
was no association between HL and age. There is no correlation between the HL and
gender in this group
135. Aman MG. Management of hyperactivity and other acting-out problems in patients with
autism spectrum disorder. Semin Pediatr Neurol 2004;11(3):225-228.
Ref ID: 4438
32
Abstract: Hyperactivity/impulsivity, aggression, self injury, and irritability are disruptive
behaviors that frequently accompany autism spectrum disorders (ASD). The
psychostimulants and atypical antipsychotics have been used with some success to
manage hyperactivity, but neither drug group is fully satisfactory and clinical response to
the stimulants varies. For other disruptive symptoms (irritability, aggression, self injury),
both older antipsychotics and newer atypical antipsychotics have been shown to have
helpful effects. Because of potential side effects, atypical antipsychotics should ordinarily
be preferred over older agents. A small group of studies suggests that selective serotonin
reuptake inhibitors may be helpful in managing symptoms related to aggression, self injury,
and the like. A small and largely imperfect literature suggests that beta blockers, mood
stabilizers, and alpha-2 agonists may also have some role for treating such symptoms.
More research is needed on the management of all of these target symptoms, both for new
agents (e.g., atomoxetine) and for established psychoactive medicines
136. Aman MG, Novotny S, Samango-Sprouse C et al. Outcome measures for clinical drug trials
in autism. CNS Spectr 2004;9(1):36-47.
Ref ID: 4440
Abstract: This paper identifies instruments and measures that may be appropriate for
randomized clinical trials in participants with autism spectrum disorders (ASDs). The
Clinical Global Impressions scale was recommended for all randomized clinical trials. At
this point, however, there is no "perfect" choice of outcome measure for core features of
autism, although we will discuss five measures of potential utility. Several communication
instruments are recommended, based in part on suitability across the age range. In trials
where the intention is to alter core features of ASDs, adaptive behavior scales are also
worthy of consideration. Several "behavior complexes" common to ASDs are identified, and
instruments are recommended for assessment of these. Given the prevalence of cognitive
impairment in ASDs, it is important to assess any cognitive effects, although cognitive data
from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related
pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine
elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics)
extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests
and assessments for continence and sleep pattern
137. Aman MG, Lam KS, Collier-Crespin A. Prevalence and patterns of use of psychoactive
medicines among individuals with autism in the Autism Society of Ohio. J Autism Dev
Disord 2003;33(5):527-534.
Ref ID: 4008
Abstract: To date, there have been few surveys of psychotropic and antiepileptic drug
(AED) prevalence in individuals with autism-spectrum conditions. We surveyed 747 families
in the Autism Society of Ohio regarding the use of psychotropic drugs, AEDs, and
over-the-counter (OTC) preparations for autism. In all, 417 families (55.8%) replied. A total
of 45.6% were taking some form of psychotropic agent (including St. John's wort and
melatonin), whereas 11.5% were taking AEDs, and 10.3% took OTC autism preparations.
The most common psychotropic agents included antidepressants (21.6%), antipsychotics
(14.9%), antihypertensives (12.5%), and stimulants (11.3%). Some 51.6% were prescribed
psychotropic drugs or AEDs, and 55.4% took psychotropic drugs, AEDs, or autism
supplements. Demographic variables frequently found to be associated with medication
use included greater age, more severe autism, more severe intellectual handicap, and
housing outside the family home. Whereas there is empirical support for the use of some of
these psychotropic agents in autism, others are being prescribed with minimal research
support. OTC autism preparations were used in substantial numbers of individuals, despite
limited research support and the possibility of toxic effects
138. Aman MG. Assessing Psychopathology and Behavior Problems in Persons with Mental
Retardation: A review of Available Instruments. Rockville, MD: US Department of Health
33
and Human Sciences; 1991.
Ref ID: 907
139. Aman MG, Singh NN. Aberrant Behavior Checklist: Manual. Aurora NY: Slossom
Educational Publications; 1986.
Ref ID: 41
140. Aman MG. Stimulant drug effects in developmental disorders and hyperactivity--toward a
resolution of disparate findings. J Autism Dev Disord 1982;12(4):385-398.
Ref ID: 2410
Abstract: An attempt is made to integrate data from a variety of clinical populations and
from the animal literature. Evidence is presented suggesting that mentally retarded and
autistic children generally show a poor response to stimulant medication, whereas
hyperactive and normal children respond beneficially. Cognitive research in mentally
retarded and autistic children is reviewed, and it is suggested that both diagnostic groups
suffer from attentional difficulties, the mechanisms of which may be very similar. The
literature on stimulant-induced stereotypy in animals is discussed, with emphasis on the
clinical implications for autism and mental retardation. An attentional model is proposed to
account for type of therapeutic response to stimulant medication. This is followed by a
possible method for testing the model and by specific predictions relating to subject
characteristics and response. [References: 82]
141. Amaral DG. The promise and the pitfalls of autism research: an introductory note for new
autism researchers. Brain Res 2011;1380:3-9.
Ref ID: 7003
Abstract: The last decade has seen an enormous growth in the quantity of research
directed at understanding the biological underpinnings of autism spectrum disorders. This
increase has been spurred on, in part, by research funding provided through private, parent
advocacy groups. While increased funding and entry into autism research by scientists
from many disciplines has facilitated the speed of discoveries germane to establishing the
etiologies of autism, there remain a number of roadblocks to understanding autism
sufficiently well to foster new treatments. This short article provides a brief overview of
some of the achievements and some of the difficulties in conducting autism research
142. Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci
2008;31(3):137-145.
Ref ID: 5601
Abstract: Autism spectrum disorder is a heterogeneous, behaviorally defined,
neurodevelopmental disorder that occurs in 1 in 150 children. Individuals with autism have
deficits in social interaction and verbal and nonverbal communication and have restricted or
stereotyped patterns of behavior. They might also have co-morbid disorders including
intellectual impairment, seizures and anxiety. Postmortem and structural magnetic
resonance imaging studies have highlighted the frontal lobes, amygdala and cerebellum as
pathological in autism. However, there is no clear and consistent pathology that has
emerged for autism. Moreover, recent studies emphasize that the time course of brain
development rather than the final product is most disturbed in autism. We suggest that the
heterogeneity of both the core and co-morbid features predicts a heterogeneous pattern of
neuropathology in autism. Defined phenotypes in larger samples of children and
well-characterized brain tissue will be necessary for clarification of the neuroanatomy of
autism
143. Amaral DG, Scharfman HE, Lavenex P. The dentate gyrus: fundamental neuroanatomical
organization (dentate gyrus for dummies). Prog Brain Res 2007;163:3-22.
Ref ID: 5793
Abstract: The dentate gyrus is a simple cortical region that is an integral portion of the
larger functional brain system called the hippocampal formation. In this review, the
34
fundamental neuroanatomical organization of the dentate gyrus is described, including
principal cell types and their connectivity, and a summary of the major extrinsic inputs of
the dentate gyrus is provided. Together, this information provides essential information that
can serve as an introduction to the dentate gyrus--a "dentate gyrus for dummies."
144. Amaral DG, Bauman MD, Capitanio JP et al. The amygdala: is it an essential component of
the neural network for social cognition? Neuropsychologia 2003;41(4):517-522.
Ref ID: 3750
Abstract: Observations from human subjects with focal brain lesions and animal subjects
with experimental lesions have implicated a variety of brain regions in the mediation of
social behavior. Previous studies carried out in the macaque monkey found that lesions of
the amygdala not only decrease emotional reactivity but also disrupt normal social
interactions. We have re-investigated the relationship between amygdala lesions and social
behavior in cohorts of mature and neonatal rhesus monkeys who were prepared with
selective and complete bilateral ibotenic acid lesions of the amygdaloid complex. These
animals display clear alterations in emotional and social behavior. We interpret these
changes as due to a loss of the ability to evaluate environmental stimuli as potential
threats. However, adult animals with bilateral lesions of the amygdala demonstrate near
normal, and even increased, social interactions with conspecifics. Moreover, neonatal
animals, prepared with amygdala lesions at 2 weeks of age, also demonstrate species
typical social behaviors such as the generation of facial expressions, grooming and play
behavior. These results argue against the idea that the amygdala is essential for the
interpretation of social communication or for the expression of social behavior. Because it
does appear to participate in the evaluation of the "safety" of social interactions, we believe
that it does have a role in modulating the amount of social behavior in which an organism
will participate. However, our current answer to the question posed in the title of this paper
is no!
145. Amaral DG, Bauman MD, Schumann CM. The amygdala and autism: implications from
non-human primate studies. Genes Brain Behav 2003;2(5):295-302.
Ref ID: 6106
Abstract: Brothers (1990) has proposed that the amygdala is an important component of
the neural network that underlies social behavior. Kemper and Bauman (1993) identified
neuropathology in the amygdala of the postmortem autistic brain. These findings, along
with recent functional neuroimaging data, have led Baron-Cohen et al. (2000) to propose
that dysfunction of the amygdala may be responsible, in part, for the impairment of social
behavior that is a hallmark feature of autism. Recent data from studies in our laboratory on
the effects of amygdala lesions in the adult and infant macaque monkey do not support a
fundamental role for the amygdala in social behavior. If the amygdala is not essential for
the component processes of social behavior, as seems to be case in both non-human
primates and selected patients with bilateral amygdala damage, then it is unlikely to be the
primary substrate for the impaired social behavior of autism. However, damage to the
amygdala does have an effect on a monkey's response to normally fear-inducing stimuli,
such as snakes, and removes a natural reluctance to engage novel conspecifics in social
interactions. These findings lead to the conclusion that an important role for the amygdala
is in the detection of threats and mobilizing an appropriate behavioral response, part of
which is fear. Interestingly, an important comorbid feature of autism is anxiety (Muris et al.
1998). If the amygdala is pathological in subjects with autism, it may contribute to their
abnormal fears and increased anxiety rather than their abnormal social behavior
146. Amaral DG, Corbett BA. The amygdala, autism and anxiety. Novartis Found Symp
2003;251:177-187.
Ref ID: 6752
Abstract: Brothers has proposed that the amygdala is an important component of the neural
network that underlies social cognition. And Bauman and Kemper observed signs of
neuropathology in the amygdala of the post-mortem autistic brain. These findings, in
35
addition to recent functional neuroimaging data, have led Baron-Cohen and colleagues to
propose that dysfunction of the amygdala may be responsible, in part, for the impairment of
social functioning that is a hallmark feature of autism. Recent data from studies in our
laboratory on the effects of amygdala lesions in the macaque monkey are at variance with
a fundamental role for the amygdala in social behaviour. If the amygdala is not essential for
normal social behaviour, as seems to be the case in both non-human primates and
selected patients with bilateral amygdala damage, then it is unlikely to be the substrate for
the abnormal social behaviour of autism. However, damage to the amygdala does have an
effect on a monkey's response to normally fear-inducing stimuli, such as snakes, and
removes a natural reluctance to engage novel conspecifics in social interactions. These
findings lead to the conclusion that an important role for the amygdala is in the detection of
threats and mobilizing an appropriate behavioural response, part of which is fear. If the
amygdala is pathological in subjects with autism, it may contribute to their abnormal fears
and increased anxiety rather than their abnormal social behaviour
147. Amati-Bonneau P, Guichet A, Olichon A et al. OPA1 R445H mutation in optic atrophy
associated with sensorineural deafness. Ann Neurol 2005;58(6):958-963.
Ref ID: 6187
Abstract: The heterozygous R445H mutation in OPA1 was found in five patients with optic
atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from
auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial
network, decreased mitochondrial membrane potential, and adenosine triphosphate
synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and
neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to
energy defects due to a fragmented mitochondrial network
148. Amato M, Donati F. Update on perinatal hypoxic insult: mechanism, diagnosis, and
interventions. Eur J Paediatr Neurol 2000;4:203-209.
Ref ID: 3116
149. Amatuzzi MG, Liberman MC, Northrop C. Selective inner hair cell loss in prematurity: a
temporal bone study of infants from a neonatal intensive care unit. J Assoc Res Otolaryngol
2011.
Ref ID: 7061
Abstract: Premature birth is a well-known risk factor for sensorineural hearing loss in
general and auditory neuropathy in particular. However, relatively little is known about the
underlying causes, in part because there are so few relevant histopathological studies.
Here, we report on the analysis of hair cell loss patterns in 54 temporal bones from
premature infants and a control group of 46 bones from full-term infants, all of whom spent
time in the neonatal intensive care unit at the Hospital de Ninos in San Jose, Costa Rica,
between 1977 and 1993. The prevalence of significant hair cell loss was higher in the
preterm group than the full-term group (41% vs. 28%, respectively). The most striking
finding was the frequency of selective inner hair cell loss, an extremely rare
histopathological pattern, in the preterm vs. the full-term babies (27% vs. 3%, respectively).
The findings suggest that a common cause of non-genetic auditory neuropathy is selective
loss of inner hair cells rather than primary damage to the cochlear nerve
150. Amatuzzi MG, Northrop C, Liberman MC et al. Selective inner hair cell loss in premature
infants and cochlea pathological patterns from neonatal intensive care unit autopsies. Arch
Otolaryngol Head Neck Surg 2001;127(6):629-636.
Ref ID: 4114
Abstract: BACKGROUND: Deafness and handicapping sensorineural hearing impairment
occur frequently in neonatal intensive care unit survivors for unknown reasons. PATIENTS
AND METHODS: Hearing was tested early and repeatedly in neonatal intensive care unit
patients with an auditory brainstem response (ABR) screener. The temporal bones of 15
nonsurvivors (30 ears) were fixed promptly (average, 5 hours) after death for histological
36
evaluation. RESULTS: Among these patients, 12 failed the ABR screen bilaterally, 1
passed unilaterally, and 2 passed bilaterally. Cochlear histopathologic conditions that could
contribute to hearing loss included bilateral selective outer hair cell loss in 2 patients,
bilateral selective inner hair cell loss in 3 (all premature), and a combination of both outer
and inner hair cell loss in 2. Other hair cell abnormalities were noted; the 2 infants who had
passed the ABR screen demonstrated normal histological features. Neuronal counts were
normal. CONCLUSIONS: Auditory brainstem response failure among these neonatal
intensive care unit infants who died was extremely common in part owing to an unexpected
histological alteration, selective inner hair cell loss among premature newborns, that should
be detectable uniquely by the ABR testing method. Additional histological patterns suggest
more than one cause for neonatal intensive care unit hearing loss. Hair cell loss patterns
seem frequently compatible with in utero damage
151. Ameli R, Courchesne E, Lincoln AJ, Kaufman A, Grillon C. Visual memory processes in
high-functioning individuals with autism. J Autism Dev Disord 1988;18:601-615.
Ref ID: 312
Abstract: High-functioning autistic individuals were compared with age-matched normal
control subjects on a visual recognition memory task. In order to evaluate the effects of
"meaning" and "delay" on the visual memory of autistic individuals, meaningful (pictures)
and meaningless (nonsense shapes) stimuli were presented visually in no delay and
1-minute delay intervals to both groups. It was concluded that autistic subjects perform
particularly poorly on meaningless material, but they are able to utilize meaning to aid their
visual memory. Contrary to expectations, 1-minute delay intervals did not differentially
affect the visual memory performance of autistic individuals compared to control subjects.
The results do not support the idea of a simple parallel between autism and mediotemporal
lobe amnesias. The visual memory performance of the autistic subjects was discussed in
the light of the possibility of a subtle involvement of the mediotemporal brain structures and
inflexible cognitive strategies poorly suited to encode novel information.
152. American Academy of Child and Adolescent Psychiatry. Summary of the practice
parameters for the assessment and treatment of children and adolescents with language
and learning disorders. Journal of the American Academy of Child & Adolescent
Psychiatry 1998;37(10):1117-1119.
Ref ID: 2588
Abstract: This summary provides an overview of the recommendations contained in the
Practice Parameters for the Assessment and Treatment of Children and Adolescents with
Language and Learning Disorders. These disorders are among the most common
developmental disorders. The diagnosis of language and learning disorders requires a
discrepancy, based on age and intelligence, between potential and achievement. The
clinician collaborates with parents and school personnel to clarify the diagnosis, implement
appropriate treatment and remediation, and monitor progress. The clinician also is
instrumental in identifying and treating comorbid conditions. Long-term prognosis depends
on the type and severity of the language or learning disorder, the availability of remediation,
and the presence of a supportive family and school environment. [References: 1]
153. American Academy of Child and Adolescent Psychiatry. Practice parameters for the
assessment and treatment of children and adolescents with language and learning
disorders. Journal of the American Academy of Child & Adolescent Psychiatry 1998;37(10
Suppl):46S-62S.
Ref ID: 2590
Abstract: These parameters describe the aims and approach to diagnosis, treatment, and
monitoring of children and adolescents with language and learning disorders (LLDs). LLDs
are among the most common developmental disorders the clinician is likely to encounter.
About 50% of children with an LLD also have a comorbid Axis I psychiatric disorder. The
diagnosis of an LLD requires a discrepancy, based on age and intelligence, between
potential and achievement. The clinician collaborates with parents and school personnel to
37
clarify the diagnosis, implement appropriate treatment and remediation, and monitor
progress. The clinician is instrumental in identifying and treating comorbid conditions,
including determining the appropriateness of medication. Long-term prognosis depends on
the type and severity of the LLD, the availability of remediation, and the presence of a
supportive family and school environment. [References: 119]
154. American Academy of Pediatrics JCoIH. Year 2007 position statement: principles and
guidelines for early hearing detection and intervention programs. Pediatrics
2007;120(4):898-921.
Ref ID: 6438
155. American Academy of Pediatrics: Committee on Children with Disabilities. The
pediatrician's role in the diagnosis and management of autistic spectrum disorder in
children. Pediatrics 2001;107(5):1221-1226.
Ref ID: 4193
Abstract: Primary care physicians have the opportunity, especially within the context of the
medical home, to be the first point of contact when parents have concerns about their
child's development or behavior. The goal of this policy statement is to help the pediatrician
recognize the early symptoms of autism and participate in its diagnosis and management.
This statement and the accompanying technical report will serve to familiarize the
pediatrician with currently accepted criteria defining the spectrum of autism, strategies used
in making a diagnosis, and conventional and alternative interventions
156. American National Standards Institute. Specifications for audiometers ANSI S3.6-1969.
New York: American National Standards Institute, Inc.; 1970.
Ref ID: 899
157. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.
Fifth Edition. 5 ed. Washington D.C.: American Psychiatric Association; 2013.
Ref ID: 7614
158. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.
Fourth edition, text revision: DSM IV-TR. 4th ed. Washington, DC.: American Psychiatric
Association; 2000.
Ref ID: 3233
159. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.
4th edition. Washington, D.C.: American Psychiatric Association; 1994.
Ref ID: 267
160. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders,
Third Edition Revised. Third, Revised ed. Washington, D.C.: American Psychiatric
Association; 1987.
Ref ID: 337
161. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders,
Third Edition. 3 ed. Washington, D.C.: American Psychiatric Association; 1980.
Ref ID: 336
162. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders,
Second Edition. 2 ed. Washington, D.C.: American Psychiatric Association; 1968.
Ref ID: 889
38
163. American Speech-Language-Hearing Association. Position Paper on Social Dialects.
September 23-24. Washington DC: ASHA; 1983.
Ref ID: 901
164. Amiel-Tison C, Stewart A. Follow up studies during the first five years of life: A pervasive
assessment of neurological function. Arch Dis Child 1989;64:496-502.
Ref ID: 1321
165. Amiet C, Gourfinkel-An I, Bouzamondo A et al. Epilepsy in autism is associated with
intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry
2008;64(7):577-582.
Ref ID: 6761
Abstract: BACKGROUND: The association between epilepsy and autism is consistently
reported, with a wide range of prevalence rates. This may be attributed to the heterogeneity
of the samples with respect to age, comorbidity, sex, and intellectual disability (ID). We
aimed to compare the prevalence of epilepsy 1) among autistic patients with ID versus
autistic patients without ID and 2) among male versus female autistic patients. METHODS:
We reviewed all data available from published reports (1963-2006) on autism and epilepsy
and conducted a meta-analysis of 10 and 14 studies, respectively, to assess the relative
risk (RR) of epilepsy in autism according to ID and gender. The pooled groups included
2112 (627 with IQ > or = 70, 1485 with IQ < 70) and 1530 (1191 male, 339 female)
patients, respectively. RESULTS: There was a strong discrepancy in relative risk (RR)
according to IQ, with more autistic patients with ID having epilepsy (RR = .555; 95%
confidence interval [CI]: .42-.73; p < .001). The pooled prevalence of epilepsy was 21.5% in
autistic subjects with ID versus 8% in autistic subjects without ID. There was a strong
discrepancy in RR according to sex, favoring comorbidity of epilepsy in autistic girls (RR =
.549; 95% CI: .45-.66; p < .001). The male:female ratio of autism comorbid with epilepsy
was close to 2:1 whereas the male:female ratio of autism without epilepsy was 3.5:1.
CONCLUSIONS: The results of this meta-analysis indicate that risk for epilepsy in autism is
a function of ID severity and distinguishes autism associated with epilepsy as a subgroup of
autism by its male-female ratio
166. Amir RE, van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is
caused by mutations in x-linked MECP2, encoding methyl-CpG-binding protein. Nat Genet
1999;23(10):185-188.
Ref ID: 2681
167. Amorosa H, von Benda U, Wagner E. Voice problems in children with unintelligible speech
as indicators of deficits in fine motor coordination. Folia Phoniatrica 1990;42:64-70.
Ref ID: 1599
168. Amorosa H, von Benda U, Dames M, Schaferskupper P. Deficits in fine moter coordination
in children with unintelligible speech. Eur Archiv Psychiatry Neurol Sci 1986;236(1):26-30.
Ref ID: 1584
169. Amunts K, Lepage C, Borgeat L et al. BigBrain: an ultrahigh-resolution 3D human brain
model. Science 2013;340(6139):1472-1475.
Ref ID: 7646
Abstract: Reference brains are indispensable tools in human brain mapping, enabling
integration of multimodal data into an anatomically realistic standard space. Available
reference brains, however, are restricted to the macroscopic scale and do not provide
information on the functionally important microscopic dimension. We created an
ultrahigh-resolution three-dimensional (3D) model of a human brain at nearly cellular
resolution of 20 micrometers, based on the reconstruction of 7404 histological sections.
"BigBrain" is a free, publicly available tool that provides considerable neuroanatomical
insight into the human brain, thereby allowing the extraction of microscopic data for
39
modeling and simulation. BigBrain enables testing of hypotheses on optimal path lengths
between interconnected cortical regions or on spatial organization of genetic patterning,
redefining the traditional neuroanatomy maps such as those of Brodmann and von
Economo
170. Amunts K, Weiss PH, Mohlberg H et al. Analysis of neural mechanisms underlying verbal
fluency in cytoarchitectonically defined stereotaxic space--the roles of Brodmann areas 44
and 45. NeuroImage 2004;22(1):42-56.
Ref ID: 4379
Abstract: We investigated neural activations underlying a verbal fluency task and
cytoarchitectonic probabilistic maps of Broca's speech region (Brodmann's areas 44 and
45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging
(fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412
(1999) 319] and developed a method to combine both data sets. In the fMRI experiment,
verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from
predefined categories. A factorial design was used with factors verbal class (semantic vs.
overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis
employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44
and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo
fMRI and postmortem MR data were warped to a common reference brain using a new
elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about
intersubject variability were calculated for both areas and superimposed on the functional
data, which showed the involvement of left hemisphere areas with verbal fluency relative to
the baseline. Semantic relative to overlearned fluency showed greater involvement of left
area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so
differentially. Left area 45 is more involved in semantic aspects of language processing,
while area 44 is probably involved in high-level aspects of programming speech production
per se. The combination of functional data analysis with a new elastic warping tool and
cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved
in language
171. Amunts K, Schleicher A, Zilles K. Outstanding language competence and cytoarchitecture
in Broca's speech region. Brain Lang 2004;89(2):346-353.
Ref ID: 4380
Abstract: Studies on brains of individuals with an exceptional mental capacity are of
widespread interest. Here, we analyze the cytoarchitecture of areas 44 and 45 (anatomical
correlates of Broca's speech region) of a person with a documented extraordinary
competence in language performance (Emil Krebs, E.K.), and compared it with 11 control
brains. Morphometry and multivariate statistical analysis revealed significant
cytoarchitectonic differences between E.K. and the controls in left and right areas 44, in
right 45, and in interhemispheric asymmetries. We conclude, that the exceptional language
competence of E.K. may be related to distinct cytoarchitectonic features in Broca's region
172. Amunts K, Schleicher A, Ditterich A, Zilles K. Broca's region: cytoarchitectonic asymmetry
and developmental changes. J Comp Neurol 2003;465(1):72-89.
Ref ID: 5797
Abstract: Functional imaging and clinical studies in children and adults have provided
evidence of developmental changes in the hemispheric specialization for language.
Whereas cytoarchitectonic asymmetry has been demonstrated in Broca's region of adults,
the anatomical correlates of developmental changes in language dominance are largely
unknown. In the present postmortem study of 34 human brains (ages ranging from 3.5
months to 85 years), the cytoarchitecture of areas 44 and 45 as the putative anatomical
correlates of Broca's region, their developmental changes, and interhemispheric asymmetry
were analyzed. Asymmetry as estimated by Euclidean distances between feature vectors
of cytoarchitectonic profiles of left and right areas 44 and 45 was already found in
1-year-old infants. Asymmetry tended to increase with age, which was significant in area
40
45, but not in area 44. An adult-like, left-larger-than-right asymmetry in the volume fraction
of cell bodies [gray level index (GLI)] was reached at approximately 5 years in area 45 and
11 years in area 44. These time points indicate a delayed development of the
cytoarchitectonic asymmetry in Broca's region in comparison with that of the primary motor
cortex. It may be hypothesized that the delayed maturation is the microstructural basis of
the development of language abilities and the influence of language practice on
cytoarchitecture during childhood. Interhemispheric asymmetry in the cytoarchitecture of
areas 44 and 45 continues to change throughout life. We conclude that the
cytoarchitectonic asymmetry of areas 44 and 45 is a result of microstructural plasticity that
endures throughout almost the whole lifespan
173. Amunts K, Jancke L, Mohlberg H, Steinmetz H, Zilles K. Interhemispheric asymmetry of the
human motor cortex related to handedness and gender. Neuropsychologia
2000;38(3):304-312.
Ref ID: 164
Abstract: Most people are right-handed, preferring the right hand for skilled as well as
unskilled activities, but a notable proportion are mixed-handed, preferring to use the right
hand for some actions and the left hand for others. Assuming a structural/functional
correlation in the motor system we tested whether asymmetries in hand performance in
consistent right and left handers as well as in mixed handers are associated with
anatomical asymmetries in the motor cortex. In vivo MR morphometry was used for
analyzing interhemispheric asymmetry in the depth of the central sulcus in the region of
cortical hand representation of 103 healthy subjects. Subjects were tested both for hand
preference and hand performance. As expected, left-right differences in hand performance
differed significantly between consistent right, consistent left and mixed handers and were
independent on gender. Male consistent right handers showed a significant deeper central
sulcus on the left hemisphere than on the right. Anatomical asymmetries decreased
significantly from male consistent right over mixed to consistent left handers. Sixty two per
cent of consistent left handers revealed a deeper central sulcus on the right than on the left
hemisphere, but for the group as a whole this rightward asymmetry was not significant. No
interhemispheric asymmetry was found in females. Thus, anatomical asymmetry was
associated with handedness only in males, but not in females, suggesting sex differences
in the cortical organization of hand movements
174. Amunts K, Schmidt-Passos F, Schleicher A, Zilles K. Postnatal development of
interhemispheric asymmetry in the cytoarchitecture of human area 4. Anat Embryol (Berl)
1997;196(5):393-402.
Ref ID: 5799
Abstract: The postnatal development of interhemispheric asymmetry was analyzed in the
primary motor cortex (area 4) of 20 human brains with quantitative cytoarchitectonic
techniques. The volume fraction of cortical tissue occupied by cell bodies (grey level index)
was determined by automated image analysis. In children as well as in adults, the volume
fraction of cell bodies averaged over all cortical layers was greater on the right than on the
left. Thus, the space between cell bodies, i.e. the volume fraction of neuropil containing
axons, dendrites and synapses, was greater in the left than in the right primary motor
cortex. At the level of single layers, however, interhemispheric asymmetry of the neuropil
volume fraction differed between age groups. The supragranular layers were significantly
less asymmetrical in children than in adults, whereas the infragranular layers showed a
similar degree of asymmetry in both age groups. Thus, the postnatal development of the
architectonic asymmetry in the supra- and infragranular layers of area 4 follows the same
sequence of maturation as found during neuronal migration, i.e. an inside-to-outside
gradient. Comparing the layer-specific developmental pattern with available functional data,
it was found that the structural maturation of interhemispheric asymmetry in the
supragranular layers correlates with the development of hand preference
41
175. An SK, Park SI, Jun SB et al. Design for a simplified cochlear implant system. IEEE Trans
Biomed Eng 2008.
Ref ID: 6426
Abstract: A simplified cochlear implant system would be appropriate for widespread use in
developing countries. Here, we describe a cochlear implant that we have designed to
realize such a concept. The system implements 8 channels of processing and stimulation
using the Continuous Interleaved Sampling (CIS) strategy. A generic Digital Signal
Processing (DSP) chip is used for the processing, and the filtering functions are performed
with a Fast Fourier Transform (FFT) of a microphone or other input. Data derived from the
processing are transmitted through an inductive link using Pulse Width Modulation (PWM)
encoding and Amplitude Shift Keying (ASK) modulation. The same link is used in the
reverse direction for backward telemetry of electrode and system information. A custom
receiver-stimulator chip has been developed that demodulates incoming data using pulse
counting and produces charge balanced biphasic pulses at 1000 pulses/s/electrode. This
chip is encased in a titanium package that is hermetically sealed using a simple but
effective method. A low cost metal-silicon hybrid mold has been developed for fabricating
an intra-cochlear electrode array with 16 ball-shaped stimulating contacts
176. Anagnostou E, Taylor MJ. Review of neuroimaging in autism spectrum disorders: what
have we learned and where we go from here. Mol Autism 2011;2(1):4.
Ref ID: 7117
Abstract: Autism spectrum disorder (ASD) refers to a syndrome of social communication
deficits and repetitive behaviors or restrictive interests. It remains a behaviorally defined
syndrome with no reliable biological markers. The goal of this review is to summarize the
available neuroimaging data and examine their implication for our understanding of the
neurobiology of ASD.Although there is variability in the literature on structural magnetic
resonance literature (MRI), there is evidence of volume abnormalities in both grey and
white matter, with a suggestion of some region-specific differences. Early brain overgrowth
is probably the most replicated finding in a subgroup of people with ASD, and new
techniques, such as cortical-thickness measurements and surface morphometry have
begun to elucidate in more detail the patterns of abnormalities as they evolve with age, and
are implicating specific neuroanatomical or neurodevelopmental processes. Functional MRI
and diffusion tensor imaging techniques suggest that such volume abnormalities are
associated with atypical functional and structural connectivity in the brain, and researchers
have begun to use magnetic resonance spectroscopy (MRS) techniques to explore the
neurochemical substrate of such abnormalities. The data from multiple imaging methods
suggests that ASD is associated with an atypically connected brain. We now need to
further clarify such atypicalities, and start interpreting them in the context of what we
already know about typical neurodevelopmental processes including migration and
organization of the cortex. Such an approach will allow us to relate imaging findings not
only to behavior, but also to genes and their expression, which may be related to such
processes, and to further our understanding of the nature of neurobiologic abnormalities in
ASD
177. Anckarsater H, Nilsson T, Stahlberg O et al. Prevalences and configurations of mental
disorders among institutionalized adolescents. Dev Neurorehabil 2007;10(1):57-65.
Ref ID: 5075
Abstract: OBJECTIVE: To assess prevalence figures for psychiatric disorders among
institutionalized adolescents due to behavioural problems and/or delinquency. METHOD:
Participants were recruited from consecutive referrals to/or treated at two Swedish
adolescent units, SIS1 (n = 60) and SIS2 (n = 70) with ranging age of 12-20.3 years (mean
age = 16.2; SD = 1.8) during 1 year. Clinical and diagnostic information was used to
generate DSM-IV diagnoses. RESULTS: One or several neuropsychiatric disorders were
diagnosed in 53% of all subjects: 39% met DSM-IV diagnostic criteria for attention
deficit/hyperactivity disorder (AD/HD), 15% for a pervasive developmental disorder
(referred to as autism spectrum disorders, ASDs) and 8% had a mental retardation
42
(referred to as a learning disability, LD). The collapsed prevalence for psychiatric disorders
requiring specialist attention was 66%, counting severe depression and psychotic disorders
but not substance use. About one in three of all adolescents in the study were given
psychopharmacological treatment. CONCLUSION: Published studies and this clinical
survey clearly indicate that systematic studies of mental health needs among
institutionalized adolescents are warranted to form the basis of adequate treatment and
support measures
178. Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social
behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U
S A 2010;107(9):4389-4394.
Ref ID: 6774
Abstract: Social adaptation requires specific cognitive and emotional competences.
Individuals with high-functioning autism or with Asperger syndrome cannot understand or
engage in social situations despite preserved intellectual abilities. Recently, it has been
suggested that oxytocin, a hormone known to promote mother-infant bonds, may be
implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin
in 13 subjects with autism. In a simulated ball game where participants interacted with
fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger
interactions with the most socially cooperative partner and reported enhanced feelings of
trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively
increased patients' gazing time on the socially informative region of the face, namely the
eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more
appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin
through its action on a core dimension of autism
179. Anderson DK, Lord C, Risi S et al. Patterns of growth in verbal abilities among children with
autism spectrum disorder. J Consult Clin Psychol 2007;75(4):594-604.
Ref ID: 5232
Abstract: Verbal skills were assessed at approximately ages 2, 3, 5, and 9 years for 206
children with a clinical diagnosis of autism (n = 98), pervasive developmental disorders-not
otherwise specified (PDD-NOS; n = 58), or nonspectrum developmental disabilities (n =
50). Growth curve analyses were used to analyze verbal skills trajectories over time.
Nonverbal IQ and joint attention emerged as strong positive predictors of verbal outcome.
The gap between the autism and other 2 groups widened with time as the latter improved
at a higher rate. However, there was considerable variability within diagnostic groups.
Children with autism most at risk for more serious language impairments later in life can be
identified with considerable accuracy at a very young age, while improvement can range
from minimal to dramatic
180. Anderson GM. The potential role of emergence in autism. Autism Research 2008;1:18-30.
Ref ID: 6504
Abstract: Abstract: Although most research on autistic behavior has considered autism
categorically, the increasingly apparent genetic and phenotypic complexities of autism are
prompting a more dimensional approach to this area. The long-standing interest in a less
categorical approach is made clear from a review of literature. The accumulating empirical
support for viewing autism-related phenomena as separable and fractionable is outlined
and includes data indicating that many of the behaviors occur in isolation in family
members and the general population, are not highly correlated within individuals, and
appear to be inherited separately. However, it is emphasized that some of the most
common and characteristic phenomena observed in individuals diagnosed with autism do
not run in their families. It is suggested that these novel, "emergent," phenomena may arise
in the individual from interacting configurations of co-occurring traits or from the interaction
of genetic and biological factors underlying the traits. A number of autism-related
phenomena including intellectual disability, seizures, persistence of primitive reflexes,
stereotypies, self-injurious behavior, savant abilities, and morphological abnormalities,
43
among others, are discussed as potentially being emergent. It is concluded that
consideration of the role of emergence in autistic behavior and related phenomena should
complement a reductionist approach and might help illuminate the components and
complexities of autism
181. Anderson GM, Zimmerman AW, Akshoomoff N, Chugani DC. Autism clinical trials:
biological and medical issues in patient selection and treatment response. CNS Spectr
2004;9(1):57-64.
Ref ID: 4356
Abstract: Biomedical measures are critical in the initial patient-screening and -selection
phases of a clinical trial in autism and related disorders. These measures can also play an
important role in the assessment and characterization of response and can provide an
opportunity to study underlying etiologic and pathophysiologic processes. Thus, biomedical
measures, including clinical laboratory analyses, metabolic screening, and chromosomal
analysis, are used to screen for potential safety-related problems, to decrease biological
and genetic heterogeneity, and to define subgroups. Neurobiological measures can be
examined as possible predictors, modifiers or surrogates of therapeutic response, and
adverse effects. Neurobiological research measures can also be used to study
mechanisms and extent of drug action and to perform baseline and longitudinal
investigations of possible pathophysiologic alterations. The potential utility and desirability
of specific measures are considered and the general approach to choosing measures for
incorporation is discussed
182. Anderson GM, Leckman JF, Cohen DJ. Neurochemical and neuropeptide systems. In:
Leckman JF, Cohen DJ, editors. Tourette's syndrome--tics, obsessions, compulsions:
Developmental psychopathology and clinical care. New York: John Wiley & Sons;
1999:261-280.
Ref ID: 2689
183. Anderson GM, Hoshino Y. Neurochemical studies of autism. In: Cohen DJ, Volkmar FR,
editors. Handbook of Autism and Pervasive Developmental Disorders. 2 ed. New York NY:
John Wiley & Sons; 1997:325-343.
Ref ID: 1930
184. Anderson GM. Studies on the neurochemistry of autism. In: Bauman ML, Kemper TL,
editors. The Neurobiology of Autism. Baltimore: Johns Hopkins University Press;
1994:227-242.
Ref ID: 124
185. Anderson GW. Thyroid hormones and the brain. Front Neuroendocrinol 2001;22(1):1-17.
Ref ID: 6076
Abstract: Significant progress has been made over the past 2 decades toward
understanding the molecular basis of thyroid hormone action. It is now widely accepted that
thyroid hormones play predominantly a nuclear role and function by regulating the
transcription of specific target genes. Understanding thyroid hormone action at the tissue
and organismic level requires assessment of the thyroid hormone response apparatus and
identification of specific target genes. Progress toward uncovering the molecular basis of
thyroid hormone action during mammalian brain development is advancing rapidly. This
commentary provides a brief overview of the molecular basis of thyroid hormone action
followed by three sections detailing thyroid hormone regulation of brain development at the
functional, cellular, and molecular levels. Each section is followed by a discussion of
unresolved issues and an analysis of our current level of understanding of each topic
186. Anderson H, Wedenberg E. Identification of normal hearing carriers of genes for deafness.
Acta Otolaryngologica (Stockh) 1978;85:40-44.
Ref ID: 787
44
187. Anderson H, Wedenberg E. Identification of normal hearing carriers of genetic deafness.
Acta Otolaryngologica (Stockh ) 1976;82:245.
Ref ID: 767
188. Anderson H, Wedenberg E. Audiometric identification of normal hearing carriers of genes
for deafness. Acta Otolaryngologica (Stockh ) 1968;65:535-554.
Ref ID: 786
189. Anderson JR, Carter CS, Fincham JM, Qin Y, Ravizza SM, Rosenberg-Lee M. Using FMRI
to test models of complex cognition. Cogn Sci 2008;32(8):1323-1348.
Ref ID: 7489
Abstract: This article investigates the potential of fMRI to test assumptions about different
components in models of complex cognitive tasks. If the components of a model can be
associated with specific brain regions, one can make predictions for the temporal course of
the BOLD response in these regions. An event-locked procedure is described for dealing
with temporal variability and bringing model runs and individual data trials into alignment.
Statistical methods for testing the model are described that deal with the scan-to-scan
correlations in the errors of measurement of the BOLD signal. This approach is illustrated
using a "sacrificial" ACT-R model that involves mapping 6 modules onto 6 brain regions in
an experiment from Ravizza, Anderson, and Carter (in press) concerned with equation
solving. The model's visual encoding predicted the BOLD response in the fusiform gyrus,
its controlled retrieval predicted the BOLD response in the lateral inferior prefrontal cortex,
and its subgoal setting predicted the BOLD response in the anterior cingulate cortex. On
the other hand, its motor programming failed to predict anticipatory activation in the motor
cortex, its representational changes failed to predicted the pattern of activity in the posterior
parietal cortex, and its procedural component failed to predict an initial spike in caudate.
The results illustrate the power of such data to direct the development of a theory of
complex problem solving, both at the level of a specific task model as well as at the level of
the cognitive architecture
190. Anderson JR. Retrieval of information from long-term memory. Science
1983;220(4592):25-30.
Ref ID: 7539
Abstract: Information is represented in long-term memory as a network of associations
among concepts. Information is retrieved by spreading activation from concepts in working
memory through the network structure. The time required to retrieve information is a
function of the level of activation that it achieves. Fanning of multiple paths from a node
dissipates the activation the node sends down any path and increases retrieval time. Fan
effects are reduced as subjects overlearn the material or when they can change their task
from a recognition judgment to a consistency judgment
191. Anderson JS, Nielsen JA, Froehlich AL et al. Functional connectivity magnetic resonance
imaging classification of autism. Brain 2011.
Ref ID: 7112
Abstract: Group differences in resting state functional magnetic resonance imaging
connectivity between individuals with autism and typically developing controls have been
widely replicated for a small number of discrete brain regions, yet the whole-brain
distribution of connectivity abnormalities in autism is not well characterized. It is also
unclear whether functional connectivity is sufficiently robust to be used as a diagnostic or
prognostic metric in individual patients with autism. We obtained pairwise functional
connectivity measurements from a lattice of 7266 regions of interest covering the entire
grey matter (26.4 million connections) in a well-characterized set of 40 male adolescents
and young adults with autism and 40 age-, sex- and IQ-matched typically developing
subjects. A single resting state blood oxygen level-dependent scan of 8 min was used for
the classification in each subject. A leave-one-out classifier successfully distinguished
autism from control subjects with 83% sensitivity and 75% specificity for a total accuracy of
45
79% (P = 1.1 x 10(-7)). In subjects <20 years of age, the classifier performed at 89%
accuracy (P = 5.4 x 10(-7)). In a replication dataset consisting of 21 individuals from six
families with both affected and unaffected siblings, the classifier performed at 71%
accuracy (91% accuracy for subjects <20 years of age). Classification scores in subjects
with autism were significantly correlated with the Social Responsiveness Scale (P = 0.05),
verbal IQ (P = 0.02) and the Autism Diagnostic Observation Schedule-Generic's combined
social and communication subscores (P = 0.05). An analysis of informative connections
demonstrated that region of interest pairs with strongest correlation values were most
abnormal in autism. Negatively correlated region of interest pairs showed higher correlation
in autism (less anticorrelation), possibly representing weaker inhibitory connections,
particularly for long connections (Euclidean distance >10 cm). Brain regions showing
greatest differences included regions of the default mode network, superior parietal lobule,
fusiform gyrus and anterior insula. Overall, classification accuracy was better for younger
subjects, with differences between autism and control subjects diminishing after 19 years of
age. Classification scores of unaffected siblings of individuals with autism were more
similar to those of the control subjects than to those of the subjects with autism. These
findings indicate feasibility of a functional connectivity magnetic resonance imaging
diagnostic assay for autism
192. Andreasen NC. Understanding the causes of schizophrenia. N Engl J Med
1999;340(8):645-647.
Ref ID: 4575
193. Andreasen NC, Flaum M, Swayze VI, et al. Intelligence and brain structure in normal
individuals. Am J Psychiatry 1993;150:130-134.
Ref ID: 2605
194. Andres M, Michaux N, Pesenti M. Common substrate for mental arithmetic and finger
representation in the parietal cortex. Neuroimage 2012;62(3):1520-1528.
Ref ID: 7558
Abstract: The history of mathematics provides several examples of the use of fingers to
count or calculate. These observations converge with developmental data showing that
fingers play a critical role in the acquisition of arithmetic knowledge. Further studies
evidenced specific interference of finger movements with arithmetic problem solving in
adults, raising the question of whether or not finger and number manipulations rely on
common brain areas. In the present study, functional magnetic resonance imaging (fMRI)
was used to investigate the possible overlap between the brain areas involved in mental
arithmetic and those involved in finger discrimination. Solving subtraction and multiplication
problems was found to increase cerebral activation bilaterally in the horizontal part of the
intraparietal sulcus (hIPS) and in the posterior part of the superior parietal lobule (PSPL).
Finger discrimination was associated with increased activity in a bilateral
occipito-parieto-precentral network extending from the extrastriate body area to the primary
somatosensory and motor cortices. A conjunction analysis showed common areas for
mental arithmetic and finger representation in the hIPS and PSPL bilaterally. Voxelwise
correlations further showed that finger discrimination and mental arithmetic induced a
similar pattern of activity within the parietal areas only. Pattern similarity was more
important for the left than for the right hIPS and for subtraction than for multiplication.
These findings provide the first evidence that the brain circuits involved in finger
representation also underlie arithmetic operations in adults
195. Andressoo JO, Weeda G, de WJ et al. An Xpb mouse model for combined xeroderma
pigmentosum and cockayne syndrome reveals progeroid features upon further attenuation
of DNA repair. Mol Cell Biol 2009;29(5):1276-1290.
Ref ID: 6044
Abstract: Patients carrying mutations in the XPB helicase subunit of the basal transcription
and nucleotide excision repair (NER) factor TFIIH display the combined cancer and
46
developmental-progeroid disorder xeroderma pigmentosum/Cockayne syndrome (XPCS).
Due to the dual transcription repair role of XPB and the absence of animal models, the
underlying molecular mechanisms of XPB(XPCS) are largely uncharacterized. Here we
show that severe alterations in Xpb cause embryonic lethality and that knock-in mice
closely mimicking an XPCS patient-derived XPB mutation recapitulate the UV sensitivity
typical for XP but fail to show overt CS features unless the DNA repair capacity is further
challenged by crossings to the NER-deficient Xpa background. Interestingly, the
Xpb(XPCS) Xpa double mutants display a remarkable interanimal variance, which points to
stochastic DNA damage accumulation as an important determinant of clinical diversity in
NER syndromes. Furthermore, mice carrying the Xpb(XPCS) mutation together with a point
mutation in the second TFIIH helicase Xpd are healthy at birth but display neonatal
lethality, indicating that transcription efficiency is sufficient to permit embryonal
development even when both TFIIH helicases are crippled. The double-mutant cells exhibit
sensitivity to oxidative stress, suggesting a role for endogenous DNA damage in the onset
of XPB-associated CS
196. Andressoo JO, Hoeijmakers JH, Mitchell JR. Nucleotide excision repair disorders and the
balance between cancer and aging. Cell Cycle 2006;5(24):2886-2888.
Ref ID: 5732
Abstract: Cancer incidence increases with age and is driven by accumulation of mutations
in the DNA. In many so-called premature aging disorders, cancer appears earlier and at
elevated rates. These diseases are predominantly caused by genome instability and
present with symptoms, including cancer, resembling "segments" of aging and are thus
often referred to as "segmental progerias". Two related segmental progerias, Cockayne
syndrome (CS) and trichothiodystrophy (TTD), don't fit this pattern. Although caused by
defects in genome maintenance via the nucleotide excision DNA repair (NER) pathway and
displaying severe progeroid symptoms, CS and TTD patients appear to lack any cancer
predisposition. More strikingly, genetic defects in the same NER pathway, and in some
cases even within the same gene, XPD, can also give rise to disorders with greatly
elevated cancer rates but without progeria (xeroderma pigmentosum). In this review, we
will discuss the connection between genome maintenance, aging and cancer in light of a
new mouse model of XPD disease
197. Andressoo JO, Hoeijmakers JH, de WH. Nucleotide excision repair and its connection with
cancer and ageing. Adv Exp Med Biol 2005;570:45-83.
Ref ID: 6043
198. Andrews AD, Barrett SF, Yoder FW, Robbins JH. Cockayne's syndrome fibroblasts have
increased sensitivity to ultraviolet light but normal rates of unscheduled DNA synthesis. J
Invest Dermatol 1978;70(5):237-239.
Ref ID: 6030
Abstract: Cockayne's syndrome is a form of cachectic dwarfism characterized by acute sun
sensitivity and numerous other abnormalities of many organ systems. We studied
fibroblasts from 9 Cockayne's syndrome patients to determine if their fibroblasts had
abnormal post-ultraviolet light colony-forming ability or abnormal ultraviolet light-induced
unscheduled DNA synthesis. The fibroblast strains from all the patients had markedly
decreased post-ultraviolet light colony-forming ability in comparison with fibroblasts from
control donors. Since this increased ultraviolet light sensitivity is propagable in vitro, it may
be a manifestation of, or be closely associated with, the inherited genetic defect of this
autosomal recessive disease. However, the patients' fibroblasts had normal rates of
ultraviolet light-induced unscheduled DNA synthesis. Thus, unlike the UV sensitivity of DNA
excision repair-deficient xeroderma pigmentosum strains, the UV sensitivity of Cockayne's
syndrome strains is not related to abnormal DNA excision repair, at least to the extent that
this repair process is reflected by rates of ultraviolet light-induced unscheduled DNA
synthesis
47
199. Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B. Thimerosal exposure in
infants and developmental disorders: a retrospective cohort study in the United kingdom
does not support a causal association. Pediatrics 2004;114(3):584-591.
Ref ID: 4291
Abstract: OBJECTIVE: After concerns about the possible toxicity of thimerosal-containing
vaccines in the United States, this study was designed to investigate whether there is a
relationship between the amount of thimerosal that an infant receives via
diphtheria-tetanus-whole-cell pertussis (DTP) or diphtheria-tetanus (DT) vaccination at a
young age and subsequent neurodevelopmental disorders. METHODS: A retrospective
cohort study was performed using 109 863 children who were born from 1988 to 1997 and
were registered in general practices in the United Kingdom that contributed to a research
database. The disorders investigated were general developmental disorders, language or
speech delay, tics, attention-deficit disorder, autism, unspecified developmental delays,
behavior problems, encopresis, and enuresis. Exposure was defined according to the
number of DTP/DT doses received by 3 and 4 months of age and also the cumulative
age-specific DTP/DT exposure by 6 months. Each DTP/DT dose of vaccine contains 50
microg of thimerosal (25 microg of ethyl mercury). Hazard ratios (HRs) for the disorders
were calculated per dose of DTP/DT vaccine or per unit of cumulative DTP/DT exposure.
RESULTS: Only in 1 analysis for tics was there some evidence of a higher risk with
increasing doses (Cox's HR: 1.50 per dose at 4 months; 95% confidence interval [CI]:
1.02-2.20). Statistically significant negative associations with increasing doses at 4 months
were found for general developmental disorders (HR: 0.87; 95% CI: 0.81-0.93), unspecified
developmental delay (HR: 0.80; 95% CI: 0.69-0.92), and attention-deficit disorder (HR:
0.79; 95% CI: 0.64-0.98). For the other disorders, there was no evidence of an association
with thimerosal exposure. CONCLUSIONS: With the possible exception of tics, there was
no evidence that thimerosal exposure via DTP/DT vaccines causes neurodevelopmental
disorders
200. Andy OJ, Jurko M. The human amygdala: excitability state and aggression. In: Sweet WH,
et al., editors. Neurosurgical treatment in psychiatry, pain, and epilepsy. Baltimore MD:
University Park Press; 1977:417-427.
Ref ID: 3051
201. Anello A, Reichenberg A, Luo X et al. Brief report: parental age and the sex ratio in autism.
J Autism Dev Disord 2009;39(10):1487-1492.
Ref ID: 6439
Abstract: The male-to-female (M:F) ratio for autism spectrum disorders (ASD), typically
about 4:1, appears to decrease with increasing paternal age, but this relationship has not
been systematically tested. With 393 ASD cases from families with two or more ASD
cases, we categorized paternal age into five age groups (<30, 30-34, 35-39, 40-44, 45+)
and found that the M:F ratio was significantly decreased with increasing paternal age
groups and remained so after also adjusting for maternal age. No significant relationship
between maternal age group and the M:F ratio was observed. This study suggests that the
M:F ratio is reduced with increasing paternal age consistent with de novo genetic or
genomic anomalies arising more frequently as men age and then conceive children
202. Angelelli P, Notarnicola A, Judica A, Zoccolotti P, Luzzatti C. Spelling impairments in Italian
dyslexic children: phenomenological changes in primary school. Cortex
2010;46(10):1299-1311.
Ref ID: 7360
Abstract: INTRODUCTION: Although spelling difficulties are constantly associated with
developmental dyslexia, they have been largely neglected by the majority of studies in this
area. This study analyzes spelling impairments in developmental dyslexia across school
grades in Italian, a language with high grapheme-to-phoneme correspondence.
METHODS: The performances of 33 Italian dyslexic children attending Grades 3 and 5
were compared with those of age-matched control participants. Writing abilities were
48
investigated through a spelling test that included regular words with one-sound-to-one-letter
correspondence, regular words requiring the application of context-sensitive conversion
rules, words with unpredictable transcription and nonwords with one-sound-to-one-letter
correspondence. RESULTS: Both accuracy and error analyses indicate that the spelling
impairment assumes different characteristics at different grades: Grade 3 children showed
an undifferentiated spelling deficit (involving regular words, regular nonwords and words
with unpredictable spelling), whereas the fifth graders were prevalently impaired in writing
words with unpredictable transcription. The error analysis confirms these results, with third
graders producing a high rate of all types of errors (i.e., phonologically plausible, simple
and context-sensitive conversion errors), whereas most errors committed by fifth graders
were phonologically plausible. CONCLUSIONS: Results are coherent with the hypothesis
that dyslexic children learning a shallow orthography suffer from delayed acquisition and
some fragility of the sub-word level routine, together with a severe and long-lasting deficit of
orthographic lexical acquisition
203. Anglin DM, Cohen PR, Chen H. Duration of early maternal separation and prediction of
schizotypal symptoms from early adolescence to midlife. Schizophr Res
2008;103(1-3):143-150.
Ref ID: 7025
Abstract: Early childhood experiences influence the capacity for healthy social and
emotional development. The present study uses longitudinal data to determine whether
early maternal separation predicted the subsequent development of schizotypal personality
disorder (SPD) symptoms assessed repeatedly from early adolescence over the following
20 years. Within this community sample (N=766), multilevel linear regression analyses
revealed the duration of separation from mother in the first 2 years of life predicted elevated
SPD symptoms. This relationship was specific to children with mother-reported early angry
emotional behavior. These results provide support for the role of early childhood
psychosocial risk factors in the development of subsequent schizophrenia spectrum
symptoms in emotionally vulnerable children
204. Angold A, Costello EJ, Erkanli A. Comorbidity. J Child Psychol Psychiatry
1999;40(1):57-87.
Ref ID: 3679
Abstract: We review recent research on the prevalence, causes, and effects of diagnostic
comorbidity among the most common groups of child and adolescent psychiatric disorders;
anxiety disorders, depressive disorders, attention deficit hyperactivity disorders,
oppositional defiant and conduct disorders, and substance abuse. A meta-analysis of
representative general population studies provides estimates of the strength of associations
between pairs of disorders with narrower confidence intervals than have previously been
available. Current evidence convincingly eliminates methodological factors as a major
cause of comorbidity. We review the implications of comorbidity for understanding the
development of psychopathology and for nosology
205. Anindya R, Aygun O, Svejstrup JQ. Damage-Induced Ubiquitylation of Human RNA
Polymerase II by the Ubiquitin Ligase Nedd4, but Not Cockayne Syndrome Proteins or
BRCA1. Mol Cell 2007;28(3):386-397.
Ref ID: 5401
Abstract: UV-induced RNA polymerase II (RNAPII) ubiquitylation and degradation are
important DNA damage responses, conserved from yeast to man. However, the identity of
the human enzymes that mediate these responses has been unclear. Previously,
Cockayne syndrome proteins and BRCA1 were implicated in the process. Surprisingly,
using a recently developed assay system, we found that these factors are not directly
involved in RNAPII ubiquitylation. The defects in RNAPII ubiquitylation observed in CS cells
are caused by an indirect mechanism: these cells shut down transcription in response to
DNA damage, effectively depleting the substrate for ubiquitylation, namely elongating
RNAPII. Instead, we identified Nedd4 as an E3 that associates with and ubiquitylates
49
RNAPII in response to UV-induced DNA damage in human cells. Nedd4-dependent
RNAPII ubiquitylation could also be reconstituted with highly purified proteins. Together,
our results indicate that transcriptional arrest at DNA lesions triggers Nedd4 recruitment
and RNAPII ubiquitylation
206. Annegers JF, Blakley SA, Hauser WA, Kurland LT. Recurrence of febrile convulsions in a
population-based cohort. Epilepsy Res 1990;5:209-216.
Ref ID: 1343
207. Annett M. The theory of an agnosic right shift gene in schizophrenia and autism. Schizophr
Res 1999;39(3):177-182.
Ref ID: 3309
Abstract: The right shift (RS) theory (Annett, M., 1972. The distribution of manual
asymmetry. Br. J. Psychol. 63, 343-358; Annett, M., 1985. Left, Right, Hand and Brain: The
Right Shift Theory. Lawrence Erlbaum, London) suggests that the typical pattern of human
cerebral and manual asymmetries depends on a single gene (RS+) which impairs
speech-related cortex of the right hemisphere. The theory offers solutions to several
puzzles, including the distribution of handedness in families (Annett, M., 1978. A Single
Gene Explanation of Right and Left Handedness and Brainedness. Lanchester Polytechnic,
Coventry; Annett, M., 1996. In defense of the right shift theory. Percept. Motor Skills 82,
115-137), relations between handedness and cerebral speech laterality (Annett, M., 1975.
Hand preference and the laterality of cerebral speech. Cortex 11, 305-328; Annett, M.,
Alexander, M.P., 1996. Atypical cerebral dominance: predictions and tests of the right shift
theory. Neuropsychologia 34, 1215-1227) and handedness and dyslexia (Annett, M. et al.,
1996. Types of dyslexia and the shift to dextrality. J. Child Psychol. Psychiatry 37,
167-180). If Crow's (Crow, T.J. et al., 1989. Schizophrenia as an anomaly of development
of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of
the disease. Arch. Gen. Psychiatry 46, 1145-1150; Crow, T.J., 1997. Is schizophrenia the
price that Homo sapiens pays for language? Schizophr. Res. 28, 127-141) theory that
schizophrenia is due to an anomaly of cerebral dominance is correct, and if the RS theory
is correct, schizophrenia could be due to an anomaly of the RS+ gene. If the RS+ gene
were at risk for a mutation which caused a loss of directional coding, the mutant could be
described as 'agnosic' for left and right. Such a gene would impair either hemisphere at
random. When paired with another RS+ gene, both hemispheres would be impaired in 50%
of cases. The other 50% and people in whom the agnosic gene is paired with an RS- allele
(neutral for asymmetry and not giving hemisphere impairment) would have one unaffected
hemisphere and, thus, normal development. Quantitative predictions based on the RS
genetic theory as previously developed, plus an agnosic mutant with frequency required to
give schizophrenia in 1% of the population, are consistent with estimates of concordance
for schizophrenia in relatives. Homozygotes of the agnosic mutant would occur at about the
rate estimated for autism
208. Anney R, Klei L, Pinto D et al. A genome-wide scan for common alleles affecting risk for
autism. Hum Mol Genet 2010;19(20):4072-4082.
Ref ID: 6867
Abstract: Although autism spectrum disorders (ASDs) have a substantial genetic basis,
most of the known genetic risk has been traced to rare variants, principally copy number
variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP)
Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide
polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In
one of four primary association analyses, the association signal for marker rs4141463,
located within MACROD2, crossed the genome-wide association significance threshold of
P < 5 x 10(-8). When a smaller replication sample was analyzed, the risk allele at
rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect
size in the replication sample was much smaller; and, for the combined samples, the
association signal barely fell below the P < 5 x 10(-8) threshold. Exploratory analyses of
50
phenotypic subtypes yielded no significant associations after correction for multiple testing.
They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2,
ST8SIA2 and TAF1C
209. Anonymous. A full genome screen for autism with evidence for linkage to a region on
chromosome 7q. International Molecular Genetic Study of Autism Consortium. Hum Mol
Genet 1998;7(3):571-578.
Ref ID: 2382
Abstract: Autism is characterized by impairments in reciprocal social interaction and
communication, and restricted and sterotyped patterns of interests and activities.
Developmental difficulties are apparent before 3 years of age and there is evidence for
strong genetic influences most likely involving more than one susceptibility gene. A
two-stage genome search for susceptibility loci in autism was performed on 87 affected sib
pairs plus 12 non-sib affected relative-pairs, from a total of 99 families identified by an
international consortium. Regions on six chromosomes (4, 7, 10, 16, 19 and 22) were
identified which generated a multipoint maximum lod score (MLS) > 1. A region on
chromosome 7q was the most significant with an MLS of 3.55 near markers D7S530 and
D7S684 in the subset of 56 UK affected sib-pair families, and an MLS of 2.53 in all 87
affected sib-pair families. An area on chromosome 16p near the telomere was the next
most significant, with an MLS of 1.97 in the UK families, and 1.51 in all families. These
results are an important step towards identifying genes predisposing to autism; establishing
their general applicability requires further study
210. Anonymous. NIH consensus conference. Cochlear implants in adults and children. JAMA
1995;274(24):1955-1961.
Ref ID: 1750
211. Anonymous. Clinical Forum. Lang Speech Hear Serv Schools 1991;22:65-88.
Ref ID: 1174
212. Anonymous. Joint Committee on Infant Hearing: Position Statement. Pediatrics
1982;70:496.
Ref ID: 783
213. Ansari D, Lyons IM, van Eimeren L, Xu F. Linking visual attention and number processing
in the brain: the role of the temporo-parietal junction in small and large symbolic and
nonsymbolic number comparison. J Cogn Neurosci 2007;19(11):1845-1853.
Ref ID: 7576
Abstract: There exists a long-standing debate regarding whether small and large
numerosities engage different networks of processing. The ability to rapidly enumerate
small (1-4) numerosities is referred to as "subitizing" and is thought to be qualitatively
different from large numerosity processing. Functional neuro-imaging studies have
attempted to dissociate neural correlates of small and large number processing by
contrasting subitizing with counting of numerosities just outside the subitizing range. In the
present study, we used functional magnetic resonance imaging (fMRI) to contrast the
processing of numerosities in the "subitizing range" with numerosities requiring estimation.
Participants compared sequentially presented slides of either dots or Arabic numerals for
their relative magnitude. We show that comparison of nonsymbolic numerosities in the
subitizing range led to activation of the right temporo-parietal junction, while at the same
time this region was found to be suppressed during large numerosity processing.
Furthermore, relative suppression of this region was strongly associated with faster
response times. In previous studies, this region has been implicated in stimulus-driven
attention. We therefore contend that activation of the temporo-parietal junction during small
number processing and the suppression thereof during large numerosity comparisons
reflects differential reliance on stimulus-driven versus goal-directed attentional networks in
the brain
51
214. Ansari D. Does the parietal cortex distinguish between "10," "ten," and ten dots? Neuron
2007;53(2):165-167.
Ref ID: 7653
Abstract: It is well established that the intraparietal sulcus (IPS) plays an important role in
the processing and representation of numerical magnitude. Two recent studies by Piazza et
al. and Cohen Kadosh et al. published in this issue of Neuron used fMRI adaptation to
explore the extent to which parietal number processing is dependent upon or independent
of a numbers' surface format. Their results, while slightly different, converge to suggest that
the answer may be neither, but rather that it depends on the hemisphere
215. Ansari D, Coch D. Bridges over troubled waters: education and cognitive neuroscience.
Trends Cogn Sci 2006;10(4):146-151.
Ref ID: 7525
Abstract: Recently there has been growing interest in and debate about the relation
between cognitive neuroscience and education. Our goal is to advance the debate beyond
both recitation of potentially education-related cognitive neuroscience findings and the
claim that a bridge between fields is chimerical. In an attempt to begin a dialogue about
mechanisms among students, educators, researchers and practitioner-scientists, we
propose that multiple bridges can be built to make connections between education and
cognitive neuroscience, including teacher training, researcher training and collaboration.
These bridges--concrete mechanisms that can advance the study of mind, brain and
education--will benefit both educators and cognitive neuroscientists, who will gain new
perspectives for posing and answering crucial questions about the learning brain
216. Antonini A, Stryker MP. Effect of sensory disuse on geniculate afferents to cat visual cortex.
Visual Neuroscience 1998;15(3):401-409.
Ref ID: 2741
Abstract: In the kitten, as little as a week of monocular lid suture during early life causes a
remarkable remodeling of the geniculocortical projections serving the deprived eye
(Antonini & Stryker, 1993a, 1996). While the physiological effects of monocular deprivation
have been shown to be due to competitive interactions between the projections serving the
two eyes, it is not known whether these morphological changes are due to competitive
interactions or to sensory disuse. We addressed this question by analyzing the morphology
of geniculocortical arbors in kittens deprived of patterned vision by binocular lid suture for 1
week or 2 weeks ending at 6 weeks of age. Such deprivation would be expected to affect
the afferents serving the two eyes equally, giving neither eye a competitive advantage. The
arbors were anterogradely filled with Phaseolus lectin iontophoretically injected into lamina
A of the lateral geniculate nucleus. The lectin was visualized immunohistochemically, and
single geniculocortical arbors were serially reconstructed in three dimensions. Arbors
reconstructed in binocularly deprived animals were compared with arbors serving the
deprived and nondeprived eye in animals monocularly deprived by lid suture of one eye for
a week and with arbors obtained in age-matched normal controls. Geniculocortical arbors
in binocularly deprived animals did not suffer the drastic remodeling of the deprived arbors
in monocularly deprived animals. Indeed, arbors in binocularly deprived animals were
indistinguishable from arbors in normal kittens or nondeprived arbors in short-term
monocularly deprived animals. These results support the notion that competitive
mechanisms rather than sensory disuse are responsible for gross morphological
remodeling of geniculocortical arbors
217. Antshel KM, Aneja A, Strunge L et al. Autistic spectrum disorders in velo-cardio facial
syndrome (22q11.2 Deletion). J Autism Dev Disord 2006.
Ref ID: 5289
Abstract: The extent to which the phenotype of children comorbid for velocardiofacial
syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS-only has
not been studied. The sample consisted of 41 children (20 females) with VCFS, ranging in
age from 6.5 years to 15.8 years. Eight children with VCFS met formal DSM-IV diagnostic
52
criteria for autism based upon the ADI-R. These eight plus an additional nine participants
met diagnostic criteria for an autistic spectrum disorder (VCFS + ASD). Ninety-four percent
of the children with VCFS + ASD had a co-occurring psychiatric disorder while 60% of
children with VCFS had a psychiatric disorder. Children with VCFS + ASD had larger right
amygdala volumes. All other neuroanatomic regions of interest were statistically similar
between the two groups
218. Anttinen A, Koulu L, Nikoskelainen E et al. Neurological symptoms and natural course of
xeroderma pigmentosum. Brain 2008;131(Pt 8):1979-1989.
Ref ID: 5796
Abstract: We have prospectively followed 16 Finnish xeroderma pigmentosum (XP)
patients for up to 23 years. Seven patients were assigned by complementation analysis to
the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of
the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient
had a different mutation (G283A). Further patients were assigned to complementation
groups on the basis of their consanguinity to an XP patient with a known complementation
group. The first sign of the disease in all the cases was severe sunburn with minimal sun
exposure in early infancy. However, at the time the diagnosis was made in only two cases.
The XP-A patients developed neurological and cognitive dysfunction in childhood. The
neurological disease advanced in an orderly fashion through its successive stages, finally
affecting the whole nervous system and leading to death before the age of 40 years.
Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C
patients were neurologically and cognitively intact despite mild brain atrophy as seen by
neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and
peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that
first presented at pre-school age. They also showed immunosuppression in cell-mediated
immunity. Neurological disease appears to be associated with the complementation group
and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not
necessarily to the severity of the dermatological symptoms, the hypersensitivity of
fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis
219. Aradhya S, Manning MA, Splendore A, Cherry AM. Whole-genome array-CGH identifies
novel contiguous gene deletions and duplications associated with developmental delay,
mental retardation, and dysmorphic features. Am J Med Genet A
2007;143A(13):1431-1441.
Ref ID: 6535
Abstract: Cytogenetic imbalances are the most frequently identified cause of developmental
delay or mental retardation, which affect 1-3% of children and are often seen in conjunction
with growth retardation, dysmorphic features, and various congenital anomalies. A
substantial number of patients with developmental delay or mental retardation are predicted
to have cytogenetic imbalances, but conventional methods for identifying these imbalances
yield positive results in only a small fraction of these patients. We used microarray-based
comparative genomic hybridization (aCGH) to study a panel of 20 patients predicted to
have chromosomal aberrations based on clinical presentation of developmental delay or
mental retardation, growth delay, dysmorphic features, and/or congenital anomalies.
Previous G-banded karyotypes and fluorescence in situ hybridization results were normal
for all of these patients. Using both oligonucleotide-based and bacterial artificial
chromosome (BAC)-based arrays on the same panel of patients, we identified 10 unique
deletions and duplications ranging in size from 280 kb to 8.3 Mb. The whole-genome
oligonucleotide arrays identified nearly twice as many imbalances as did the
lower-resolution whole-genome BAC arrays. This has implications for using aCGH in a
clinical setting. Analysis of parental DNA samples indicated that most of the imbalances
had occurred de novo. Moreover, seven of the 10 imbalances represented novel disorders,
adding to an increasing number of conditions caused by large-scale deletions or
duplications. These results underscore the strength of high-resolution genomic arrays in
diagnosing cases of unknown genetic etiology and suggest that contiguous genomic
53
alterations are the underlying pathogenic cause of a significant number of cases of
developmental delay
220. Aram DM, Eisele JA. Limits to a left hemisphere explanation for specific language
impairment. Journal of Speech & Hearing Research 1994;37(4):824-830.
Ref ID: 2630
Abstract: The hypothesis of unilateral left hemisphere damage as an explanatory model for
the neurological basis of specific language impairment (SLI) does not appear to be
sufficient for most children with SLI. Children with unilateral brain lesions have been shown
to function significantly lower than their neurologically intact peers on a variety of language
measures, yet few of the deficits noted are as persistent or severe as those seen in SLI. In
at least two instances, however, language symptomatology following unilateral lesions in
children does parallel some types of SLI. The first occurs following subcortical damage to
anterior grey and white matter structures that typically results in pronounced language and
learning disorders. The second parallel lies in the similar developmental course shared by
children with "delayed" language and children with known unilateral lesions, whereby
language onset and development is slow in the preschool years but normalizes by school
age, with minimal long-term language-learning deficits. [References: 57]
221. Aram DM, Eisele JA. Intellectual stability in children with unilateral brain lesions.
Neuropsychologia 1994;32(1):85-95.
Ref ID: 2832
Abstract: In this paper we report on the longitudinal stability of IQ in 26 children with
unilateral left (LL N = 18) or right (RL N = 8) hemisphere damage. Results revealed (i)
normal or near normal levels of intellectual performance in both LL and RL groups, and, (ii)
hemispheric differences in the level and stability of intellectual performance. RL children
achieved lower IQ scores than LL children and were more likely to decrease in VIQ over
time. Cross-sectional analyses revealed a tendency for injury sustained earlier (e.g. during
the first 5 years of age), rather than later in development to be associated with lower IQ
scores
222. Aram DM, Morris R, Hall NE. Clinical and research congruence in identifying children with
specific language impairment. Journal of Speech & Hearing Research 1993;36(3):580-591.
Ref ID: 2642
Abstract: This paper reports on the results of a large multicenter project designed to
develop an empirically based classification of preschool children with language
impairments. A clinically selected population of 252 children with specific language
impairments (SLI) was used to evaluate the reliability, coverage, and usefulness of both
standard clinical and research definitions of such children. Varying degrees of congruence
were found between the clinically identified children with SLI and those identified as SLI
using discrepancy, deficit, and standardized operational criteria. Such mismatch between
the original clinical identification and more standardized operational criteria may be related
to different clinical perspectives, professional training, and limited assessment measures.
These results suggest that there is a significant gulf between the clinical diagnosis of
children with specific language impairment and more standardized operational criteria. It is
suggested that the global concept of a "specific language impairment" may not be a useful
concept for either clinical or research activities
223. Aram DM, Eisele JA. Plasticity and recovery of higher cognitive functions following early
brain injury. In: Rapin I, Segalowitz SJ, editors. Section 10: Child Neuropsychology (Part 1).
4 ed. Amsterdam NL: Elsevier Science; 1992:73-92.
Ref ID: 710
224. Aram DM, Morris R, Hall NE. The validity of discrepancy criteria for identifying children with
developmental language disorders. J Learn Disabil 1992;25(9):549-554.
Ref ID: 2628
54
Abstract: Empirical data from two studies address the clinical validity of discrepancy criteria
for identification of children with developmental language disorders (DLD). Study 1 involved
256 preschoolers clinically defined as DLD and meeting inclusionary criteria for normal
hearing, intellectual, neurological, and psychiatric status. Application of alternative
psychometrically derived discrepancy criteria identified only 40% to 60% of the clinically
defined group as language disordered. Study 2 applied nonverbal IQ-language
performance discrepancy criteria to 368 eight-year-old, randomly selected control subjects,
resulting in over 45% of the controls being identified as DLD. Factors contributing to
underidentification in Study 1 and over-identification in Study 2 are discussed, raising
questions regarding the validity of discrepancy criteria for identification of DLD children
225. Aram DM. Comments on specific language impairment as a clinical category. Lang Speech
Hear Serv Schools 1991;22:84-87.
Ref ID: 908
226. Aram DM, Hack M, Hawkins S, Weissman BM, Borawski-Clark E. Very-low-birthweight
children and speech and language development. Journal of Speech & Hearing Research
1991;34(5):1169-1179.
Ref ID: 2646
Abstract: Very low birthweight (VLBW) is often considered to be a risk factor for speech and
language disorders, yet data are equivocal. The present study compared speech and
language comprehension and production between 249 very-low-birthweight (VLBW: less
than 1.5 kg) and 363 normal-birthweight 8-year-olds, randomly sampled in a geographic
area. Mean performance for the entire group of VLBW children and for the group when 24
VLBW children with major neurologic abnormalities were excluded, was significantly lower
than for controls on the majority of speech and language measures. Further analyses
addressed the clinical significance of these statistically significant differences. Test scores
were converted to standard scores and grouped according to standard deviation intervals,
thus portraying each child's performance in terms of the magnitude of discrepancy from
each test's mean. When the 24 children with major neurological abnormalities were
excluded, no significant differences between the VLBW and control children were
observed. Using discrepancy between WISC-R performance IQ and language to define
specific language impairment (SLI), a higher percentage of control than VLBW children
were identified as having SLI. Neonatal risk factors did not differentiate between VLBW
children with or without SLI. A higher proportion of VLBW than control children did present
subnormal language associated with IQ less than 85, hearing deficits, and/or major
neurological impairments. Thus, SLI is not more common among VLBW than control
children. Language deficits accompanied by more general developmental problems,
however, are more frequent. [References: 53]
227. Aram DM. Language sequelae of unilateral brain lesions in children. In: Plum F, editor.
Language, communication and the brain. New York: Raven Press; 1988:171-197.
Ref ID: 2824
228. Aram DM, Ekelman BL, Whitaker HA. Spoken syntax in children with acquired unilateral
hemisphere lesions. Brain Lang 1986;27(1):75-100.
Ref ID: 2828
Abstract: The spoken syntax of eight left hemisphere lesioned and eight right hemisphere
lesioned children were compared to matched controls. The children's lesions were acquired
between 0.08 and 6.17 years of age (mean = 1.33 years), and at the time of testing they
were between 1.67 and 8.15 years of age (mean = 4.19). Based on analyses of
spontaneous language samples, left hemisphere lesioned subjects performed more poorly
than did their controls on most measures of simple and complex sentence structure. In
contrast right lesioned subjects performed similarly to their controls on these measures,
except for a tendency to make more errors in simple sentence structures. These findings
55
provide further evidence that the left and right hemispheres are not comparable in
supporting syntactic abilities
229. Aram DM, Ekelman BL, Rose DF, Whitaker HA. Verbal and cognitive sequelae following
unilateral lesions acquired in early childhood. Journal of Clinical & Experimental
Neuropsychology 1985;7(1):55-78.
Ref ID: 2829
Abstract: Eight left-hemisphere lesioned children and eight right-hemisphere lesioned
children between 18 months and 8 years of age were compared to control subjects on a
battery of intelligence and language measures. Both left- and right-lesioned subjects had
lower IQ scores than their controls, yet most functioned within the normal range or higher.
Lexical comprehension and production were depressed in both subject groups and
appeared to be depressed to a greater degree in right-lesioned subjects than in those with
left lesions. In contrast, syntactic production in left-lesioned subjects was markedly deficient
in comparison to controls as well as right-lesioned subjects. Although both subjects and
controls included children with articulation errors, the number of misarticulating children and
misarticulated sounds was greatest in the left-lesioned group. Finally, fluency disorders
were observed in both right- and left-lesioned subjects but were not observed in controls.
The study provides further evidence that the right and left hemispheres are not
equipotential for language and that left-hemisphere lesions acquired early in childhood
impair syntactic development to a greater degree than do right-hemisphere lesions
230. Aram DM, Ekelman BL, Nation JE. Preschoolers with language disorders: 10 years later.
Journal of Speech & Hearing Research 1984;27(2):232-244.
Ref ID: 2831
Abstract: Language, intelligence, academic achievement, and behavioral adjustment were
assessed in a group of 20 adolescents originally studied 10 years earlier as preschoolers
with language disorders. At follow-up, 20% had WISC-R IQ scores in the mentally deficient
range and were being educated in EMR classrooms. Of the remaining 16, 11 (69%) had
required special tutoring, grade retention, or LD class placement. The majority of non-EMR
subjects continued to evidence persistent deficits in language and academic achievement
and were rated by their parents as being less socially competent and having more
behavioral problems than their peers. Of the initial preschool measures available, the Leiter
was found to be the best single predictor of intelligence, language, class placement, and
reading achievement in adolescence, although the NSST: Expressive subtest also was a
strong predictor of adolescent language
231. Aram DM, Rose DF, Rekate HL, Whitaker HA. Acquired capsular/striatal aphasia in
childhood. Arch Neurol 1983;40(10):614-617.
Ref ID: 2826
Abstract: We studied a case of language loss caused by an acquired vascular lesion in the
putamen, anterior limb of the internal capsule, and lateral aspect of the head of the caudate
nucleus in a 7-year-old right-handed girl. Acute right-sided hemiplegia, mutism, oral
apraxia, and disturbance in language comprehension but no dysarthria were present.
During recovery, a nonfluent aphasia with anomia was evident. After six months, only mild
hemiparesis and minor spelling difficulties persisted. We compared this patient with an
11-year-old right-handed girl with right-sided hemiparesis and dysarthria but no language
loss following a lesion in the globus pallidus, a portion of the posterior limb of the internal
capsule, and the body of the caudate. The presence of a language disturbance in the first
but not the second patient was attributed to the difference in lesion location. The symptoms
and lesions were similar to those in recent reports of adult patients. To our knowledge, this
is the first report of these findings in a child with a left-hemisphere lesion
232. Aram DM, Nation JE. Preschool language disorders and subsequent language and
academic difficulties. J Commun Disord 1980;13(2):159-170.
Ref ID: 6972
56
Abstract: Sixty-three language-disordered children first evaluated in their preschool years
were followed four to five years after initial diagnosis. At follow-up approximately 40% of
these children continued to present speech and language problems and approximately
40% presented other learning problems. Preschool levels of language comprehension,
formulation, semantics, syntax, phonology, and speech production were found to be
moderately correlated to subsequent class placement in the elementary grades. Duration of
preschool therapy was not related to either the severity of preschool language disorder or
to any subsequent speech, language, or academic abilities. Duration of school therapy was
related to severity of phonologic deficit as rated during the preschool years and to all
follow-up ratings for speech, language, and academic abilities
233. Aram DM, Nation JE. Patterns of language behavior in children with developmental
language disorders. J Speech Hear Res 1975;18:229-241.
Ref ID: 6973
Abstract: 47 DLD kids. Factor analysis: 3 factors, 6 subtypes: 1. repetition stregth; 2.
non-specific formulation-repetition deficit; 3. generalized low performance; 4. phonologic
comprehension-repetition deficit; 5. Comprehension deficit; 6. formulation-repetition deficit
234. Aran A, Shalev RS, Biran G, Gross-Tsur V. Parenting style impacts on quality of life in
children with cerebral palsy. J Pediatr 2007.
Ref ID: 5000
235. Arbelle S, Sigman MD, Kasari C. Compliance with parental prohibition in autistic children. J
Autism Dev Disord 1994;24:693-702.
Ref ID: 1217
236. Arcelus J, Vostanis P. Psychiatric comorbidity in children and adolescents. Curr Opin
Psychiatry 2005;18(4):429-434.
Ref ID: 7186
Abstract: PURPOSE OF REVIEW: This review critically discusses recent research findings
on psychiatry comorbidity in children and adolescent persons. RECENT FINDINGS:
Several epidemiological studies have confirmed previous findings in relation to the high
rates of psychiatric comorbidity in children and adolescents. In particular, psychiatric
comorbidity has been detected in children with substance abuse, and with conduct and
oppositional defiant, anxiety and attention deficit-hyperactivity disorders. These studies
have also investigated the impact comorbidity has on symptom presentation, outcome and
service utilization. Although the presence of concurrent psychiatric disorders in children and
adolescents is well established, there has been limited research on the need for different
treatment modalities in children suffering from more than one disorder. SUMMARY: It is
widely accepted that children and adolescents frequently present with more than one
psychiatric diagnosis. The substantial variation in psychiatric comorbidity found in the
literature may be due to the different methods of data collection as well as to the
classification system used. Whether children and adolescents fulfil diagnostic criteria for a
mixed condition (International Classification of Diseases-10) or multiple disorders
(Diagnostic and Statistical Manual of Mental Disorders-IV), it is important that the
concurrent psychopathology be recognized and treated
237. Ariella RR, Ritvo ER, Guthrie D, Ritvo MJ. Clinical evidence that Asperger's disorder is a
mild form of autism. Compr Psychiatry 2008;49(1):1-5.
Ref ID: 149
Abstract: OBJECTIVE: The aim of this study is to obtain clinical evidence to test the
hypothesis that Asperger's disorder (AD) is a mild form of autism (AU). METHOD: A
78-item Likert scale (the RAADS) was administered to 25 adults with AD and 19 with AU
(ages, 18-65 years) to assess presence, type, and duration of symptoms. RESULTS: The
following results were found: (a) subjects with AD and AU have similar symptoms
throughout adulthood (responses to 72 of 78 questions were not significantly different); (b)
57
subjects with AD had a significantly fewer total number of symptoms; (c) subjects with AD
reported nonsignificantly fewer symptoms in the DSM-IV-TR domains of social interaction
and repetitive patterns of behavior; and (d) subjects with AD had significantly fewer
symptoms in the communication domain. CONCLUSIONS: The data support the
hypothesis that AD is a mild form of AU, and that they share a common etiology and
developmental neuropathology. It appears warranted in future diagnostic manuals to
incorporate AU and AD into 1 diagnostic category such as, "Autism Spectrum Disorder,
(with modifiers, severe, moderate, mild, atypical, and Asperger's type)."
238. Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol 2005;20(9):747-753.
Ref ID: 4749
Abstract: Rett syndrome is a sporadic disorder (except for a few familial cases) occurring in
1 in 10,000 to 1 in 23,000 girls worldwide. It is associated with profound mental and motor
handicap. About 90% of cases involve a mutation in the methyl-CpG binding protein 2 gene
(MECP2). The role of this gene in the pathogenesis of this enigmatic disorder is being
extensively investigated in animal models. Rett syndrome is associated with a complex
phenotype that is unique in every aspect of its presentation, clinical physiology, chemistry,
and pathology. Years of concentrated observations have defined the clinical presentation of
classic Rett syndrome and its variants and related features (eg, neurophysiologic,
radiologic, chemical, metabolic, and anatomic). This article reviews the neuropathology of
Rett syndrome, which involves individual neurons, perhaps selected neurons, of decreased
size, dendritic branching, and numbers of spines. This article also summarizes the studies
in the human and mouse brain with Rett syndrome that are beginning to reveal the
disorder's pathoetiology
239. Arnold LE, Vitiello B, McDougle C et al. Parent-defined target symptoms respond to
risperidone in RUPP autism study: customer approach to clinical trials. J Am Acad Child
Adolesc Psychiatry 2003;42(12):1443-1450.
Ref ID: 4441
Abstract: OBJECTIVE: A consumer-oriented efficacy assessment in clinical trials should
measure changes in chief complaint and consumer request (symptoms of most concern to
patient/caregiver), which may be diluted in change scores of multisymptom scales.
METHOD: In the Research Units on Pediatric Psychopharmacology (RUPP) Autism
Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of
parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary
measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a
9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable
data. RESULTS: The most common symptoms identified by parents were tantrums,
aggression, and hyperactivity. Interrater reliability was excellent. Mean ratings at endpoint
were 2.8 +/- 1.2 on risperidone and 4.5 +/- 1.3 on placebo (p <.001). Ratings were collinear
with Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability
subscale (primary dimensional measure). Effect size d was 1.4, compared to 1.2 on the
Aberrant Behavior Checklist Irritability subscale. Effect sizes varied twofold by symptom
category, largest for self-injury (2.11) and tantrums (1.95). CONCLUSIONS: Risperidone
was superior to placebo in reducing symptoms of most concern to parents of autistic
children with irritable behavior. Rating individualized participant-chosen target symptoms
seems a reliable, sensitive, efficient, and consumer-friendly way to assess treatment effect
and might have clinical application
240. Arnold LE, Aman MG, Martin A et al. Assessment in multisite randomized clinical trials of
patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric
Psychopharmacology. J Autism Dev Disord 2000;30(2):99-111.
Ref ID: 3833
Abstract: Assessment of autistic disorder (autism) symptoms, primary and secondary,
poses more challenging problems than ordinarily found in multisite randomized clinical trial
(RCT) assessments. For example, subjects may be uncommunicative and extremely
58
heterogeneous in problem presentation, and current pharmacological treatments are not
likely to alter most core features of autism. The Autism Research Units on Pediatric
Psychopharmacology (RUPP Autism Network) resolved some of these problems during the
design of a risperidone RCT in children/adolescents. The inappropriateness of the usual
anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining
uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The
communication problems, compromising use of the patient as an informant, were
addressed by several strategies, including careful questioning of care providers, rating
scales, laboratory tests, and physical exams. The broad subject heterogeneity requires
outcome measures sensitive to individual change over a wide spectrum of treatment
response and side effects. The problems of neuropsychologically testing nonverbal, lower
functioning, sometimes noncompliant subjects requires careful instrument
selection/adaptation and flexible administration techniques. The problems of assessing
low-end IQs, neglected by most standardized test developers, was resolved by an
algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and
neuropsychological tests and lack of standardization required development of a new,
specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most
valid diagnostic instrument) and other clinician instruments required extensive cross-site
training (in-person, videotape, and teleconference sessions). Definition of a treatment
responder required focus on individually relevant target symptoms, synthesis of possible
modest improvements in many domains, and acceptance of attainable though imperfect
goals. The assessment strategy developed is implemented in a RCT of risperidone
(McDougle et al., 2000) for which the design and other methodological challenges are
described elsewhere (Scahill et al., 2000). Some of these problems and solutions are
partially shared with RCTs of other treatments and other disorders
241. Arnold SR, Spicer D, Kouseff B, Lacson A, Gilbert-Barness E. Seckel-like syndrome in
three siblings. Pediatr Dev Pathol 1999;2(2):180-187.
Ref ID: 3070
Abstract: Seckel syndrome has been described as the prototype of the primordial
bird-headed type of dwarfism. Since Seckel originally defined the disorder, less than 60
cases have been reported. In addition to the characteristic craniofacial dysmorphism and
skeletal defects, abnormalities have been described in the cardiovascular, hematopoietic,
endocrine, and central nervous systems. This pleiotropy has implied genetic heterogeneity
and prompted reviews of previously reported cases of Seckel syndrome. As a result, the
characteristic diagnostic features of Seckel syndrome have been highly debated. Although
deletions in chromosome 2q have been described, to date, no genetic defect has been
defined. We report three cases of Seckel-like syndrome in siblings from nonconsanguinous
Caucasian parents. In addition to the typical Seckel phenotypic features, all three cases
were characterized by severe hydrocephalus. We review the literature and propose that
there is a spectrum of Seckel conditions that share some common key features, but also
demonstrate a wide range of phenotypic features
242. Arnold W, Ganzer U, Kleinmann H. Sensorineural hearing loss in mucous otitis. Archives of
Otorhinolaryngology 1977;215:91-93.
Ref ID: 583
243. Arrieta I, Lobato MN, Martinez B, Criado B. Parental origin of Robertsonian translocation
(15q22q) and Prader Willi syndrome associated with autism [letter]. Psychiatr Genet
1994;4(1):63-65.
Ref ID: 3254
244. Arsalidou M, Duerden EG, Taylor MJ. The centre of the brain: Topographical model of
motor, cognitive, affective, and somatosensory functions of the basal ganglia. Hum Brain
Mapp 2012.
Ref ID: 7675
59
Abstract: The basal ganglia have traditionally been viewed as motor processing nuclei;
however, functional neuroimaging evidence has implicated these structures in more
complex cognitive and affective processes that are fundamental for a range of human
activities. Using quantitative meta-analysis methods we assessed the functional
subdivisions of basal ganglia nuclei in relation to motor (body and eye movements),
cognitive (working-memory and executive), affective (emotion and reward) and
somatosensory functions in healthy participants. We document affective processes in the
anterior parts of the caudate head with the most overlap within the left hemisphere.
Cognitive processes showed the most widespread response, whereas motor processes
occupied more central structures. On the basis of these demonstrated functional roles of
the basal ganglia, we provide a new comprehensive topographical model of these nuclei
and insight into how they are linked to a wide range of behaviors. Hum Brain Mapp, 2012.
(c) 2012 Wiley Periodicals, Inc
245. Arsalidou M, Taylor MJ. Is 2+2=4? Meta-analyses of brain areas needed for numbers and
calculations. Neuroimage 2011;54(3):2382-2393.
Ref ID: 7676
Abstract: Most of us use numbers daily for counting, estimating quantities or formal
mathematics, yet despite their importance our understanding of the brain correlates of
these processes is still evolving. A neurofunctional model of mental arithmetic, proposed
more than a decade ago, stimulated a substantial body of research in this area. Using
quantitative meta-analyses of fMRI studies we identified brain regions concordant among
studies that used number and calculation tasks. These tasks elicited activity in a set of
common regions such as the inferior parietal lobule; however, the regions in which they
differed were most notable, such as distinct areas of prefrontal cortices for specific
arithmetic operations. Given the current knowledge, we propose an updated topographical
brain atlas of mental arithmetic with improved interpretative power
246. Arshad S, Winterhalder R, Underwood L et al. Epilepsy and intellectual disability: does
epilepsy increase the likelihood of co-morbid psychopathology? Res Dev Disabil
2011;32(1):353-357.
Ref ID: 7110
Abstract: Although epilepsy is particularly common among people with intellectual disability
(ID) it remains unclear whether it is associated with an increased likelihood of co-morbid
psychopathology. We therefore investigated rates of mental health problems and other
clinical characteristics in patients with ID and epilepsy (N = 156) as compared to patients
with ID but no epilepsy (N = 596). All participants were consecutive referrals to specialist
mental heath services. Specialist clinicians agreed on the mental health diagnoses by
applying ICD-10 clinical criteria using information gained from interviews with key
informants and the patients. Bivariate and multivariate analyses showed that patients with
epilepsy were more likely to live in residential housing and have severe ID in line with
previous evidence. However, the presence of epilepsy was not associated with an
increased likelihood of co-morbid psychopathology. On the contrary, rates of mental health
problems, including schizophrenia spectrum, personality and anxiety disorders, were
significantly lower among patients with epilepsy. The results are discussed in the context of
mood-stabilizing and other psychotropic effects of anti-epileptic drugs in adults with ID and
epilepsy, as well as possible diagnostic overshadowing
247. Arthur G. A Point Scale of Performance Tests. Revised Form II. New York: Psychological
Corporation; 1972.
Ref ID: 534
248. Arthur G. The Arthur Adaption of the Leiter International Performance Scale. Washington,
DC: Psychological Service Center Press; 1952.
Ref ID: 900
60
249. Artieres F, Vieu A, Mondain M, Uziel A, Venail F. Impact of early cochlear implantation on
the linguistic development of the deaf child. Otol Neurotol 2009;30(6):736-742.
Ref ID: 6413
Abstract: OBJECTIVE: The purpose of this study was to examine prognostic factors of
cochlear implantation and to evaluate the impact of early implantation on linguistic
development in deaf children. STUDY DESIGN: Retrospective study. SETTING: Tertiary
referral center. PATIENTS: Seventy-four prelingually deafened children implanted before
the age of 5 years. INTERVENTION: Annual follow-up after cochlear implantation. MAIN
OUTCOME MEASURES: Speech perception, intelligibility, and expressive and receptive
language scores from age 3 to 8 years were globally compared between 4 subgroups of
children. Significant differences were further explored by intergroup comparisons. Stepwise
logistic linear regression was performed using the following variables: age at implantation,
duration of cochlear implant (CI) use, preoperative hearing levels, age of hearing aid (HA)
fitting, and age at time of the evaluation. Preoperative data were not available. RESULTS:
Between group comparisons displayed significant differences according to age at
implantation. Multivariate analysis demonstrated the positive impact of early implantation
on receptive language. Moreover, duration of CI use and preoperative hearing levels were
statistically correlated with performance on speech perception, intelligibility, and expressive
and receptive language. Age of HA fitting was associated with speech intelligibility.
CONCLUSION: Age at implantation, duration of CI, preoperative hearing levels, and age of
HA fitting may each be useful in predicting linguistic success after cochlear implantation.
Other factors such as preoperative linguistic development may also influence postoperative
outcomes, but the lack of tests suitable for use with very young children makes such a
hypothesis difficult to confirm
250. Artigas J. [Language in autistic disorders]. Rev Neurol (Paris) 1999;28 Suppl 2:S118-S123.
Ref ID: 3302
Abstract: Autism is a developmental disorder affecting social relationships, communication
and flexibility of thought. These three basic aspects of autism may present in many different
forms and degrees. Therefore autism should be considered to be a spectrum of autistic
disorders rather than a single strictly defined condition. The spectrum of autistic disorders
extends from intelligent individuals with acceptable social integration, to severely retarded
patients with scarcely any social interaction. Language is almost always affected either in
its formal aspects or in its usage. Autistic linguistic disorders form a specific language
disorder (developmental dysphasia) and a pragmatic disorder linked both to the primary
language problem and to the social cognitive deficit. We discuss the different linguistic
syndromes observed in autistic patients with special emphasis on the semantic- pragmatic
disorder
251. Asano E, Pawlak C, Shah A et al. The diagnostic value of initial video-EEG monitoring in
children--review of 1000 cases. Epilepsy Res 2005;66(1-3):129-135.
Ref ID: 4939
Abstract: OBJECTIVE: We retrospectively reviewed the clinical utility of initial video-EEG
monitoring in a series of 1000 children suspected of epileptic disorders. METHODS: The
ages of patients (523 boys and 477 girls) ranged from 1 month to 17 years (median age: 7
years). The mean length of stay was 1.5 days (range: 1-10 days). Outcomes were
classified as: 'useful-epileptic' (successful classification of epilepsy), 'useful-nonepileptic'
(demonstration of nonepileptic habitual events), 'uneventful' (normal EEG without habitual
events captured), and 'inconclusive' (inability to clarify the nature of habitual events with
abnormal interictal EEG findings). RESULTS: A total of 315 studies were considered
'useful-epileptic'; 219 'useful-nonepileptic'; 224 'uneventful'; 242 'inconclusive'. Longer
monitoring was associated with higher rate of a study classified as 'useful-epileptic' in all
age groups (Chi square test: p<0.001). In addition, longer monitoring was associated with
lower rate of a study classified as 'inconclusive' in adolescences (p<0.001). Approximately
half of the children with successful classification of epilepsy were assigned a specific
diagnosis of epilepsy syndrome according to the International League Against Epilepsy
61
(ILAE) classification. We found only 22 children with ictal EEG showing a seizure onset
purely originating from a unilateral temporal region. CONCLUSION: Video-EEG monitoring
may fail to capture habitual episodes. To maximize the utility of studies in the future, a
video-EEG monitoring longer than 3 days should be considered in selected children such
as adolescences with habitual events occurring on a less than daily basis. We recognize a
reasonable clinical utility of the current ILAE classification in the present study. It may not
be common to identify children with pure unilateral temporal lobe epilepsy solely based on
video-EEG monitoring
252. Asano E, Chugani DC, Muzik O et al. Autism in tuberous sclerosis complex is related to
both cortical and subcortical dysfunction. Neurology 2001;57(7):1269-1277.
Ref ID: 3463
Abstract: OBJECTIVE: To examine the relationship between autism and epilepsy in relation
to structural and functional brain abnormalities in children with tuberous sclerosis complex
(TSC). METHODS: Children with TSC and intractable epilepsy underwent MRI as well as
PET scans with 2-deoxy-2- [(18)F]fluoro-D-glucose (FDG) and
alpha-[(11)C]methyl-L-tryptophan (AMT). Based on the results of Autism Diagnostic
Interview-Revised, Gilliam Autism Rating Scale, and overall adaptive behavioral composite
(OABC) from Vineland Adaptive Behavior Scale, subjects were divided into three groups:
autistic (OABC < 70; n = 9), mentally-retarded nonautistic (OABC < 70; n = 9), and
relatively normal intelligence (OABC > or = 70; n = 8). RESULTS: PET studies showed that
the autistic group had decreased glucose metabolism in the lateral temporal gyri bilaterally,
increased glucose metabolism in the deep cerebellar nuclei bilaterally, and increased AMT
uptake in the caudate nuclei bilaterally, compared to the mentally-retarded nonautistic
group. In addition, a history of infantile spasms and glucose hypometabolism in the lateral
temporal gyri were both significantly associated with communication disturbance. Glucose
hypermetabolism in the deep cerebellar nuclei and increased AMT uptake in the caudate
nuclei were both related to stereotypical behaviors and impaired social interaction, as well
as communication disturbance. CONCLUSIONS: These results suggest that generalized
epilepsy in early life and functional deficits in the temporal neocortices may be associated
with communication delays, and that functional imbalance in subcortical circuits may be
associated with stereotypical behaviors and impaired social interaction in children with TSC
253. Asarnow JA. Annotation: Childhood-onset schizophrenia. J Child Psychol Psychiatry
1994;35(8):1345-1371.
Ref ID: 1505
254. Asarnow R. Childhood-onset schizophrenia. In: Segalowitz SJ, Rapin I, editors. Handbook
of Neuropsychology, Vol VII: Child Neuropsychology. Amsterdam Elsevier Science:
1992:443-456.
Ref ID: 118
255. Asarnow R, Sherman T, Strandburg R. The search for the psychobiological substrate of
childhood onset schizoprhenia. J Am Acad Child Psychiatry 1986;26:601-604.
Ref ID: 902
256. Ashcraft MH, Yamashita TS, Aram DM. Mathematics performance in left and right
brain-lesioned children and adolescents. Brain Cognit 1992;19(2):208-252.
Ref ID: 2827
Abstract: Children and adolescents with unilateral left- or right-hemisphere lesions were
administered a standardized test of mathematics ability and a battery of experimental tests
that examined the components of numerical and arithmetic processing. All lesioned groups
showed at least marginally lower scores on the standardized test than the controls. More
importantly, lesion-related deficits in performance were observed, especially for younger
left-lesioned subjects (ages 7-12), on the verbal counting, digit matching, speeded addition,
and written subtraction tasks; deficits among younger right-lesioned subjects were similar in
62
nature, yet less pronounced than in the left-hemisphere group. Older left-lesioned subjects
showed differences from their controls only on complex verbal counting and speeded
addition. Correlations among the various measures indicated two further points. First,
earlier onset of left-hemisphere lesion is associated with more serious disruption of
mathematical processing. Second, these disruptions are not well assessed by a typical
standardized test of mathematical performance, but are clearly in evidence with more
precise, focused tasks
257. Ashe PC, Berry MD, Boulton AA. Schizophrenia, a neurodegenerative disorder with
neurodevelopmental antecedents. Prog Neuropsychopharmacol Biol Psychiatry
2001;25(4):691-707.
Ref ID: 7056
Abstract: Schizophrenia is a devastating disorder that has been referred to as youth's
greatest disabler. Although a number of hypotheses have been proposed in an attempt to
explain the pathophysiology of schizophrenia no single theory seems to account for all
facets of the disease. Each hypothesis explains some of the phenomena associated with
schizophrenia and it is probable that many variables described in these hypotheses interact
to produce a disorder characterized by heterogeneous symptomatology, progression and
prognosis. Compelling evidence suggests that the primary disturbance is a
neurodevelopmental abnormality, possibly resulting from a genetic defect(s), resulting in a
predisposition to schizophrenia. Events later in life may then lead to the presentation of
symptoms and a subsequent progression of the disease. Recent evidence suggests that
the progressive course of schizophrenia is associated with ongoing neurodegenerative
processes. Changes in brain derived neurotrophic factor (BDNF) may explain the various
changes observed in schizophrenia
258. Ashkenazi S, Rosenberg-Lee M, Tenison C, Menon V. Weak task-related modulation and
stimulus representations during arithmetic problem solving in children with developmental
dyscalculia. Dev Cogn Neurosci 2012;2 Suppl 1:S152-S166.
Ref ID: 7332
Abstract: Developmental dyscalculia (DD) is a disability that impacts math learning and skill
acquisition in school-age children. Here we investigate arithmetic problem solving deficits in
young children with DD using univariate and multivariate analysis of fMRI data. During fMRI
scanning, 17 children with DD (ages 7-9, grades 2 and 3) and 17 IQ- and reading
ability-matched typically developing (TD) children performed complex and simple addition
problems which differed only in arithmetic complexity. While the TD group showed strong
modulation of brain responses with increasing arithmetic complexity, children with DD failed
to show such modulation. Children with DD showed significantly reduced activation
compared to TD children in the intraparietal sulcus, superior parietal lobule, supramarginal
gyrus and bilateral dorsolateral prefrontal cortex in relation to arithmetic complexity.
Critically, multivariate representational similarity revealed that brain response patterns to
complex and simple problems were less differentiated in the DD group in bilateral anterior
IPS, independent of overall differences in signal level. Taken together, these results show
that children with DD not only under-activate key brain regions implicated in mathematical
cognition, but they also fail to generate distinct neural responses and representations for
different arithmetic problems. Our findings provide novel insights into the neural basis of
DD
259. Ashley-Koch A, Wolpert CM, Menold MM et al. Genetic studies in autistic disorder and
chromosome 7. Genomics 1999;61(3):227-236.
Ref ID: 3093
260. Ashley-Koch AE, Jaworski J, Ma dQ et al. Investigation of potential gene-gene interactions
between APOE and RELN contributing to autism risk. Psychiatr Genet 2007;17(4):221-226.
Ref ID: 5515
Abstract: BACKGROUND: Several candidate gene studies support RELN as susceptibility
63
gene for autism. Given the complex inheritance pattern of autism, it is expected that
gene-gene interactions will exist. A logical starting point for examining potential gene-gene
interactions is to evaluate the joint effects of genes involved in a common biological
pathway. RELN shares a common biological pathway with APOE, and Persico et al. have
observed transmission distortion of the APOE-2 allele in autism families. OBJECTIVE: We
evaluated RELN and APOE for joint effects in autism susceptibility. METHODS: A total of
470 Caucasian autism families were analyzed (265 multiplex; 168 trios with no family
history; 37 positive family history but only one sampled affected). These families were
genotyped for 11 RELN polymorphisms, including the 5' untranslated region repeat
previously associated with autism, as well as for the APOE functional allele. We evaluated
single locus allelic and genotypic association with the pedigree disequilibrium test and
geno-PDT, respectively. Multilocus effects were evaluated using the extended version of
the multifactorial dimensionality reduction method. RESULTS: For the single locus
analyses, there was no evidence for an effect of APOE in our data set. Evidence for
association with RELN (rs2,073,559; trio subset P=0.07 PDT; P=0.001 geno-PDT; overall
geno-PDT P=0.05), however, was found. For multilocus geno-PDT analysis, the joint
genotype of APOE and RELN rs2,073,559 was highly significant (trio subset, global
P=0.0001), probably driven by the RELN single locus effect. Using the extended version of
the multifactorial dimensionality reduction method to detect multilocus effects, there were
no statistically significant associations for any of the n-locus combinations involving RELN
or APOE in the overall or multiplex subset. In the trio subset, 1-locus and 2-locus models
selected only markers in RELN as best models for predicting autism case status.
CONCLUSION: Thus, we conclude that there is no main effect of APOE in our autism data
set, nor is there any evidence for a joint effect of APOE with RELN. RELN, however,
remains a good candidate for autism susceptibility
261. Ashwin C, Baron-Cohen S, Wheelwright S, O'Riordan M, Bullmore ET. Differential
activation of the amygdala and the 'social brain' during fearful face-processing in Asperger
Syndrome. Neuropsychologia 2007;45(1):2-14.
Ref ID: 5313
Abstract: Impaired social cognition is a core feature of autism. There is much evidence
showing people with autism use a different cognitive style than controls for face-processing.
We tested if people with autism would show differential activation of social brain areas
during a face-processing task. Thirteen adults with high-functioning autism or Asperger
Syndrome (HFA/AS) and 13 matched controls. We used fMRI to investigate 'social brain'
activity during perception of fearful faces. We employed stimuli known to reliably activate
the amygdala and other social brain areas, and ROI analyses to investigate brain areas
responding to facial threat as well as those showing a linear response to varying threat
intensities. We predicted: (1) the HFA/AS group would show differential activation (as
opposed to merely deficits) of the social brain compared to controls and (2) that social brain
areas would respond to varied intensity of fear in the control group, but not the HFA/AS
group. Both predictions were confirmed. The controls showed greater activation in the left
amygdala and left orbito-frontal cortex, while the HFA/AS group showed greater activation
in the anterior cingulate gyrus and superior temporal cortex. The control group also showed
varying responses in social brain areas to varying intensities of fearful expression, including
differential activations in the left and right amygdala. This response in the social brain was
absent in the HFA/AS group. HFA/AS are associated with different patterns of activation of
social brain areas during fearful emotion processing, and the absence in the HFA/AS brain
of a response to varying emotional intensity
262. Ashwin E, Ashwin C, Rhydderch D, Howells J, Baron-Cohen S. Eagle-eyed visual acuity:
an experimental investigation of enhanced perception in autism. Biol Psychiatry 2008.
Ref ID: 5854
Abstract: BACKGROUND: Anecdotal accounts of sensory hypersensitivity in individuals
with autism spectrum conditions (ASC) have been noted since the first reports of the
condition. Over time, empirical evidence has supported the notion that those with ASC
64
have superior visual abilities compared with control subjects. However, it remains unclear
whether these abilities are specifically the result of differences in sensory thresholds
(low-level processing), rather than higher-level cognitive processes. METHODS: This study
investigates visual threshold in n = 15 individuals with ASC and n = 15 individuals without
ASC, using a standardized optometric test, the Freiburg Visual Acuity and Contrast Test, to
investigate basic low-level visual acuity. RESULTS: Individuals with ASC have significantly
better visual acuity (20:7) compared with control subjects (20:13)-acuity so superior that it
lies in the region reported for birds of prey. CONCLUSIONS: The results of this study
suggest that inclusion of sensory hypersensitivity in the diagnostic criteria for ASC may be
warranted and that basic standardized tests of sensory thresholds may inform causal
theories of ASC
263. Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+
lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J
Neuroimmunol 2006;173(1-2):126-134.
Ref ID: 5167
Abstract: Gastrointestinal pathology, characterized by lymphoid nodular hyperplasia and
entero-colitis, has been demonstrated in a cohort of children with autistic spectrum disorder
(ASD). Systemic and intestinal mucosal immune dysregulation was assessed in ASD
children with gastrointestinal (GI) symptoms (n = 18), and typically developing controls (n =
27), including non-inflamed controls (NIC) and inflamed GI control children with Crohn's
disease (CD), by analysis of intracellular cytokines in CD3+ lymphocytes. In both peripheral
blood and mucosa, CD3+ TNFalpha+ and CD3+ IFNgamma+ were increased in ASD
children compared with NIC (p < 0.004) and reached levels similar to CD. In contrast,
peripheral and mucosal CD3+ IL-10+ were markedly lower in ASD children with GI
symptoms compared with both NIC and CD controls (p < 0.02). In addition, mucosal CD3+
IL-4+ cells were increased (p < 0.007) in ASD compared with NIC. There is a unique
pattern of peripheral blood and mucosal CD3+ lymphocytes intracellular cytokines, which is
consistent with significant immune dysregulation, in this ASD cohort
264. Ashwood P, Wills S, Van de WJ. The immune response in autism: a new frontier for autism
research. J Leukoc Biol 2006;80(1):1-15.
Ref ID: 5182
Abstract: Autism spectrum disorders (ASD) are part of a broad spectrum of
neurodevelopmental disorders known as pervasive developmental disorders, which occur
in childhood. They are characterized by impairments in social interaction, verbal and
nonverbal communication and the presence of restricted and repetitive stereotyped
behaviors. At the present time, the etiology of ASD is largely unknown, but genetic,
environmental, immunological, and neurological factors are thought to play a role in the
development of ASD. Recently, increasing research has focused on the connections
between the immune system and the nervous system, including its possible role in the
development of ASD. These neuroimmune interactions begin early during embryogenesis
and persist throughout an individual's lifetime, with successful neurodevelopment
contingent upon a normal balanced immune response. Immune aberrations consistent with
a dysregulated immune response, which so far, have been reported in autistic children,
include abnormal or skewed T helper cell type 1 (T(H)1)/T(H)2 cytokine profiles, decreased
lymphocyte numbers, decreased T cell mitogen response, and the imbalance of serum
immunoglobulin levels. In addition, autism has been linked with autoimmunity and an
association with immune-based genes including human leukocyte antigen (HLA)-DRB1 and
complement C4 alleles described. There is potential that such aberrant immune activity
during vulnerable and critical periods of neurodevelopment could participate in the
generation of neurological dysfunction characteristic of ASD. This review will examine the
status of the research linking the immune response with ASD
265. Ashwood P, Anthony A, Torrente F, Wakefield AJ. Spontaneous mucosal lymphocyte
cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune
65
activation and reduced counter regulatory interleukin-10. J Clin Immunol
2004;24(6):664-673.
Ref ID: 5473
Abstract: A lymphocytic enterocolitis has been reported in a cohort of children with autistic
spectrum disorder (ASD) and gastrointestinal (GI) symptoms. This study tested the
hypothesis that dysregulated intestinal mucosal immunity with enhanced pro-inflammatory
cytokine production is present in these ASD children. Comparison was made with
developmentally normal children with, and without, mucosal inflammation. Duodenal and
colonic biopsies were obtained from 21 ASD children, and 65 developmentally normal
paediatric controls, of which 38 had signs of histological inflammation. Detection of CD3+
lymphocyte staining for spontaneous intracellular TNFalpha, IL-2, IL-4, IFNgamma, and
IL-10, was performed by multicolor flow cytometry. Duodenal and colonic mucosal CD3+
lymphocyte counts were elevated in ASD children compared with noninflamed controls
(p<0.03). In the duodenum, the proportion of lamina propria (LP) and epithelial
CD3(+)TNFalpha+ cells in ASD children was significantly greater compared with
noninflamed controls (p<0.002) but not coeliac disease controls. In addition, LP and
epithelial CD3(+)IL-2+ and CD3(+)IFNgamma+, and epithelial CD3(+)IL-4+ cells were more
numerous in ASD children than in noninflamed controls (p<0.04). In contrast, CD3(+)IL-10+
cells were fewer in ASD children than in noninflamed controls (p<0.05). In the colon, LP
CD3(+)TNFalpha+ and CD3(+)IFNgamma+ were more frequent in ASD children than in
noninflamed controls (p<0.01). In contrast with Crohn's disease and non-Crohn's colitis, LP
and epithelial CD3(+)IL-10+ cells were fewer in ASD children than in nondisease controls
(p<0.01). There was a significantly greater proportion of CD3(+)TNFalpha+ cells in colonic
mucosa in those ASD children who had no dietary exclusion compared with those on a
gluten and/or casein free diet (p<0.05). There is a consistent profile of CD3+ lymphocyte
cytokines in the small and large intestinal mucosa of these ASD children, involving
increased pro-inflammatory and decreased regulatory activities. The data provide further
evidence of a diffuse mucosal immunopathology in some ASD children and the potential for
benefit of dietary and immunomodulatory therapies
266. Aslin RN, Schlaggar BL. Is myelination the precipitating neural event for language
development in infants and toddlers? Neurology 2006;66(3):304-305.
Ref ID: 4788
267. Asperger H. 'Autistic psychopathy' (translation and annotation by U. Frith of the original
Asperger1944
german paper: Asperger H (1944). "Die "Autistischen Psychopathen" im Kindesalter
[Autistic psychopats in childhood]" (in German). Archiv für psychiatrie und
nervenkrankheiten 117: 76-136. http://www.springerlink.com/content/u350x0683r1g6432/).
In: Frith U, editor. Autism and Asperger Syndrome. Cambridge UK: Cambridge University
Press; 1991:37-92.
Ref ID: 895
268. Asperger H. Problems of infantile autism. Communication 1979;13:45-52.
Ref ID: 1595
269. Asperger H. Die "Autistischen Psychopathen" im Kindesalter (translated by U. Frith, 1991,
[see ref 895]. Archiv für Psychiatrie und Nervenkrankheiten 1944;117:76-136.
Ref ID: 7163
Abstract: Traslatd and annoted by U. Frith: 'Autistic psychopathy'
270. Asthagiri AR, Parry DM, Butman JA et al. Neurofibromatosis type 2. Lancet
2009;373(9679):1974-1986.
Ref ID: 6344
Abstract: Neurofibromatosis type 2 is an autosomal-dominant multiple neoplasia syndrome
that results from mutations in the NF2 tumour suppressor gene located on chromosome
66
22q. It has a frequency of one in 25,000 livebirths and nearly 100% penetrance by 60 years
of age. Half of patients inherit a germline mutation from an affected parent and the
remainder acquire a de novo mutation for neurofibromatosis type 2. Patients develop
nervous system tumours (schwannomas, meningiomas, ependymomas, astrocytomas, and
neurofibromas), peripheral neuropathy, ophthalmological lesions (cataracts, epiretinal
membranes, and retinal hamartomas), and cutaneous lesions (skin tumours). Optimum
treatment is multidisciplinary because of the complexities associated with management of
the multiple, progressive, and protean lesions associated with the disorder. We review the
molecular pathogenesis, genetics, clinical findings, and management strategies for
neurofibromatosis type 2
271. Astuto LM, Weston MD, Carney CA et al. Genetic heterogeneity of Usher syndrome:
analysis of 151 families with Usher type I. Am J Hum Genet 2000;67(6):1569-1574.
Ref ID: 4060
Abstract: Usher syndrome type I is an autosomal recessive disorder marked by hearing
loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci
USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most
common subtype. In our analysis, 151 families with Usher I were screened by linkage and
mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the
remaining 87 families, who were negative for MYO7A mutations, 54 were informative for
linkage analysis and were screened with the remaining USH1 loci markers. Results of
linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However,
one maximum LOD score was observed lying within the USH1D region. Two lesser peak
LOD scores were observed outside and between the putative regions for USH1D and
USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity
across the USH1D, USH1F, and intervening regions. These results provide conclusive
evidence that the second-most-common subtype of Usher I is due to genes on
chromosome 10, and they confirm the existence of one Usher I gene in the previously
defined USH1D region, as well as providing evidence for a second, and possibly a third,
gene in the 10p/q region
272. Atladottir HO, Pedersen MG, Thorsen P et al. Association of family history of autoimmune
diseases and autism spectrum disorders. Pediatrics 2009;124(2):687-694.
Ref ID: 6569
Abstract: OBJECTIVES: Recent studies suggest that familial autoimmunity plays a part in
the pathogenesis of ASDs. In this study we investigated the association between family
history of autoimmune diseases (ADs) and ASDs/infantile autism. We perform confirmatory
analyses based on results from previous studies, as well as various explorative analyses.
METHODS: The study cohort consisted of all of the children born in Denmark from 1993
through 2004 (689 196 children). Outcome data consisted of both inpatient and outpatient
diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in
parents and siblings of the cohort members was obtained from the Danish National
Hospital Register. The incidence rate ratio of autism was estimated by using log-linear
Poisson regression. RESULTS: A total of 3325 children were diagnosed with ASDs, of
which 1089 had an infantile autism diagnosis. Increased risk of ASDs was observed for
children with a maternal history of rheumatoid arthritis and celiac disease. Also, increased
risk of infantile autism was observed for children with a family history of type 1 diabetes.
CONCLUSIONS: Associations regarding family history of type 1 diabetes and infantile
autism and maternal history of rheumatoid arthritis and ASDs were confirmed from previous
studies. A significant association between maternal history of celiac disease and ASDs was
observed for the first time. The observed associations between familial autoimmunity and
ASDs/infantile autism are probably attributable to a combination of a common genetic
background and a possible prenatal antibody exposure or alteration in fetal environment
during pregnancy
67
273. Atladottir HO, Parner ET, Schendel D, Dalsgaard S, Thomsen PH, Thorsen P. Time trends
in reported diagnoses of childhood neuropsychiatric disorders: a Danish cohort study. Arch
Pediatr Adolesc Med 2007;161(2):193-198.
Ref ID: 5272
Abstract: OBJECTIVES: To examine trends in autism (autism spectrum disorder and
childhood autism) in the context of 3 additional childhood neuropsychiatric disorders:
hyperkinetic disorder, Tourette syndrome, and obsessive-compulsive disorder. DESIGN:
Population-based cohort study. SETTING: Children were identified in the Danish Medical
Birth Registry. Relevant outcomes were obtained via linkage with the Danish National
Psychiatric Register, which included reported diagnoses through 2004 by psychiatrists
using diagnostic criteria from the International Statistical Classification of Diseases, 10th
Revision. PARTICIPANTS: All children born in Denmark from 1990 through 1999, a total of
669 995 children. MAIN OUTCOME MEASURES: Cumulative incidence proportion by age,
stratified by year of birth, for each disorder. RESULTS: Statistically significant increases
were found in cumulative incidence across specific birth years for autism spectrum
disorder, childhood autism, hyperkinetic disorder, and Tourette syndrome. No significant
change in cumulative incidence was observed for obsessive-compulsive disorder.
CONCLUSIONS: Recent increases in reported autism diagnoses might not be unique
among childhood neuropsychiatric disorders and might be part of a more widespread
epidemiologic phenomenon. The reasons for the observed common pattern of change in
reported cumulative incidence could not be determined in this study, but the data
underscore the growing awareness of and demand for services for children with
neurodevelopmental disorders in general
274. Atmaca M, Yildirim H, Ozdemir H, Tezcan E, Poyraz AK. Volumetric MRI study of key brain
regions implicated in obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol
Psychiatry 2007;31(1):46-52.
Ref ID: 5602
Abstract: Neuroanatomic abnormalities have been implicated in the pathophysiology of
obsessive-compulsive disorder (OCD). To date, no study has measured the orbito-frontal
cortex (OFC), anterior cingulate, caudate nucleus, and thalamus concurrently in
first-episode patients. Thus, we performed a volumetric MRI study in patients who were
treatment-naive and healthy controls focusing on the in vivo neuroanatomy of the whole
brain, total gray and white matter volume, thalamus, caudate nucleus, anterior cingulate
cortex, and OFC concurrently. The volumes of thalamus, caudate nucleus, anterior
cingulate cortex, and OFC were measured in 12 OCD patients who were treatment-naive
and 12 healthy control subjects. Anterior cingulate and OFC volumes included both white
and gray matters. Volumetric measurements were made with T1-weighted coronal MRI
images, with 1.5-mm-thick slices, at 1.5 T. The patients had increased white matter volume
than healthy controls. The patient group had significantly smaller left and right OFC
volumes and significantly greater left and right thalamus volumes compared with healthy
controls. Anterior cingulate exhibited a near-significant difference between the patients and
healthy controls on left side. Significant correlations were found between Y-BOCS scores
and left OFC, and right OFC, and between Y-BOCS and left thalamus volumes in the
patient group. In conclusion, our findings suggest that abnormalities in these areas may
play an important role in the pathophysiology of OCD
275. Attias J, Raveh E. Transient deafness in young candidates for cochlear implants. Audiol
Neurootol 2007;12(5):325-333.
Ref ID: 6174
Abstract: This study describes 5 infants who were diagnosed with auditory neuropathy (AN)
associated with severe to profound neural hearing loss shortly after birth. However, on
repetition of the tests 7-12 months later, all infants showed full or partial recovery. The
follow-up electrophysiological patterns were characterized by the appearance of wave I,
followed by wave III and V, reflecting synchronization of auditory pathways and
improvement in auditory nerve function. Suspected causative or contributory factors were
68
neonatal hyperbilirubinemia, hypoxia, ischemia, and central nervous system immaturity,
alone or in combination. These findings indicate that lack of an auditory brain stem
response does not necessarily mean no hearing and that the situation where AN exists can
improve. Thus, clinicians should be made aware that although cochlear implants may yield
better auditory performance when applied early, they should be considered a therapeutic
option only after repeated measures have proved persistent AN, and no child should be
considered for an implant until a behavioral measure of hearing has been obtained
276. Auer T, Pinter S, Kovacs N et al. Does obstetric brachial plexus injury influence speech
dominance? Ann Neurol 2009;65(1):57-66.
Ref ID: 6001
Abstract: OBJECTIVE: Right-handedness and left-sided language lateralization is an
unresolved mystery with unknown cause/effect relations. Most studies suggest that the
language lateralization is related to a fundamental brain asymmetry: right-handedness may
be secondary. We analyzed the possibility of an opposite cause/effect relation: whether
asymmetric hand usage (as a cause) can influence language lateralization (as a
consequence). METHODS: We determined language lateralization by functional magnetic
resonance imaging in 15 subjects whose upper limb (UL) had been injured at birth because
of unilateral damage of the brachial plexus. These subjects were able to use only one (the
noninjured) UL perfectly. RESULTS: We found correlation between the severity of
right-sided UL injuries and hand usage dysfunction and the degree of left-to-right shift of
language lateralization. There was, however, not a complete switch of language
lateralization. INTERPRETATION: Right-sided UL injury can induce a left-to-right shift in
language lateralization, suggesting that hand usage can influence language lateralization.
These findings may contradict the broadly accepted theory that right-handedness is a
secondary phenomenon caused by left-sided hemispheric language lateralization.
However, the cause/effect problem between asymmetric hand usage and language
lateralization is not resolved in this study. Our findings may support the theory that gestures
had a crucial role in human language evolution and is a part of the language system even
today
277. August G, Raz N, Baird R. Fenfluramine response in high and low functioning autistic
children. J Am Acad Child Adolesc Psychiatry 1987;26:342-346.
Ref ID: 905
278. Augustsson I, Engstand I. Otitis media and academic achievements. Int J Pediatr
Otorhinolaryngol 2001;57(1):31-40.
Ref ID: 3322
279. Auriemmo J, Kuk F, Lau C et al. Effect of linear frequency transposition on speech
recognition and production of school-age children. J Am Acad Audiol 2009;20(5):289-305.
Ref ID: 6381
Abstract: PURPOSE: To investigate the clinical efficacy of linear frequency transposition
(LFT) for a group of school-age children. RESEARCH DESIGN: A nonrandomized,
within-subject design was implemented to investigate vowel and consonant recognition and
fricative articulation of school-age children utilizing this feature. STUDY SAMPLE: Ten
children, aged 6 years and 3 months, to 13 years and 6 months from a special education
school district participated in this study. Individual hearing thresholds ranged from normal to
moderate in the low frequencies and from severe to profound in the high frequencies.
Average language age of children was within 2.2 years of chronological age. DATA
COLLECTION AND ANALYSIS: Phoneme recognition and fricative articulation
performance were compared for three conditions: (1) with the children's own hearing aids,
(2) with an advanced hearing instrument utilizing LFT, and (3) with the same instrument
without LFT. Nonsense syllable materials were administered at 30 and 50 dB HL input
levels. Fricative articulation was measured by analyzing speech samples of conversational
speech and oral reading passages. Repeated measures general linear model was utilized
69
to determine the significance of any noted effects. RESULTS: Results indicated significant
improvements in vowel and consonant recognition with LFT for the 30 dB HL input level.
Significant improvement in the accuracy of production of high-frequency (HF) fricatives
after six weeks of use of LFT was also observed. CONCLUSIONS: These results suggest
that LFT is a potentially useful hearing aid feature for school-age children with a precipitous
HF sensorineural hearing loss
280. Aust G. Vestibulotoxicity and ototoxicity of gentamicin in newborns at risk. Int Tinnitus J
2001;7(1):27-29.
Ref ID: 4087
Abstract: Gentamicin is a potentially ototoxic drug routinely used for treatment of
life-threatening infectious diseases in neonatology. In study 1, of 8,333 children examined
for hearing disorders, 134 (1.6%) had received previous treatment with gentamicin. Only
eight (6.0%) suffered from various extents of sensorineural hearing impairment, and all
eight had a history of other risk factors of hearing loss (e.g., perinatal asphyxia, acidosis,
icterus gravis, or meningitis). In study 2, 30 children (mean age, 13.2 months) with normal
hearing had received gentamicin during the newborn phase, and 30 healthy children of
similar age without previous gentamicin treatment were examined for vestibular function.
Neither in the number of spontaneous eye movements nor in the means of the nystagmus
parameters of the rotatory test did the data show any significant difference between the
groups. The results indicate that gentamicin in controlled therapeutic doses has a less
ototoxic and vestibulotoxic effect in newborns than it does in older children or in adults
281. Autilio LA, Norton WT, Terry RD. THE PREPARATION AND SOME PROPERTIES OF
PURIFIED MYELIN FROM THE CENTRAL NERVOUS SYSTEM. J Neurochem
1964;11:17-27.
Ref ID: 7692
282. Autret A, Lucas B, Billard C et al. Sleep and inter-ictal electroencephalographic epileptic
activities. In: Beaumanoir A, Bureau M, Deonna T, Mira L, Tassinari CA, editors.
Continuous Spikes and Waves during Slow Sleep - Electrical Status Epilepticus during
Slow Sleep: Acquired Epileptic Aphasia and Related Conditions. 1 ed. London, UK: John
Libbey; 1995:65-76.
Ref ID: 2157
283. Auyeung B, Taylor K, Hackett G, Baron-Cohen S. Foetal testosterone and autistic traits in
18 to 24-month-old children. Mol Autism 2010;1(1):11.
Ref ID: 6745
Abstract: ABSTRACT: BACKGROUND: Autism spectrum conditions have been
characterised as an extreme presentation of certain male-typical psychological traits. In
addition, several studies have established a link between prenatal exposure to testosterone
and cognitive sex differences in later life, and one study found that foetal testosterone (FT)
is positively correlated to autistic traits in 6 to 10 year-old children. In this study, we tested
whether FT is positively correlated with autistic traits in toddlers aged 18-24 months.
METHODS: Levels of FT were analysed in amniotic fluid and compared with autistic traits,
measured using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in 129 typically
developing toddlers aged between 18 and 24 months (mean +/- SD 19.25 +/- 1.52 months).
RESULTS: Sex differences were observed in Q-CHAT scores, with boys scoring
significantly higher (indicating more autistic traits) than girls. In addition, we confirmed a
significant positive relationship between FT levels and autistic traits. CONCLUSIONS: The
current findings in children between 18 and 24 months of age are consistent with
observations in older children showing a positive association between elevated FT levels
and autistic traits. Given that sex steroid-related gene variations are associated with autistic
traits in adults, this new finding suggests that the brain basis of autistic traits may reflect
individual differences in prenatal androgens and androgen-related genes. The consistency
70
of findings in early childhood, later childhood and adulthood suggests that this is a robust
association
284. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G. Fetal
testosterone and autistic traits. Br J Psychol 2009;100(Pt 1):1-22.
Ref ID: 6582
Abstract: Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is
related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has
also been suggested that autism may be an extreme manifestation of some male-typical
traits, both in terms of cognition and neuroanatomy. In this paper, we examine the
possibility of a link between autistic traits and fT levels measured in amniotic fluid during
routine amniocentesis. Two instruments measuring number of autistic traits (the Childhood
Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ-Child)) were
completed by these women about their children (N=235), ages 6-10 years. Intelligence
Quotient (IQ) was measured in a subset of these children (N=74). fT levels were positively
associated with higher scores on the CAST and AQ-Child. This relationship was seen
within sex as well as when the sexes were combined, suggesting this is an effect of fT
rather than of sex per se. No relationships were found between overall IQ and the predictor
variables, or between IQ and CAST or AQ-Child. These findings are consistent with the
hypothesis that prenatal androgen exposure is related to children exhibiting more autistic
traits. These results need to be followed up in a much larger sample to test if clinical cases
of ASC have elevated fT
285. Auyeung B, Baron-Cohen S, Ashwin E et al. Fetal testosterone predicts sexually
differentiated childhood behavior in girls and in boys. Psychol Sci 2009;20(2):144-148.
Ref ID: 6746
Abstract: Mammals, including humans, show sex differences in juvenile play behavior. In
rodents and nonhuman primates, these behavioral sex differences result, in part, from sex
differences in androgens during early development. Girls exposed to high levels of
androgen prenatally, because of the genetic disorder congenital adrenal hyperplasia, show
increased male-typical play, suggesting similar hormonal influences on human
development, at least in females. Here, we report that fetal testosterone measured from
amniotic fluid relates positively to male-typical scores on a standardized questionnaire
measure of sex-typical play in both boys and girls. These results show, for the first time, a
link between fetal testosterone and the development of sex-typical play in children from the
general population, and are the first data linking high levels of prenatal testosterone to
increased male-typical play behavior in boys
286. Auyeung B, Baron-Cohen S, Wheelwright S, Allison C. The Autism Spectrum Quotient:
Children's Version (AQ-Child). J Autism Dev Disord 2008;38(7):1230-1240.
Ref ID: 6747
Abstract: The Autism Spectrum Quotient-Children's Version (AQ-Child) is a parent-report
questionnaire that aims to quantify autistic traits in children 4-11 years old. The range of
scores on the AQ-Child is 0-150. It was administered to children with an autism spectrum
condition (ASC) (n = 540) and a general population sample (n = 1,225). Results showed a
significant difference in scores between those with an ASC diagnosis and the general
population. Receiver-operating-characteristic analyses showed that using a cut-off score of
76, the AQ-Child has high sensitivity (95%) and specificity (95%). The AQ-Child showed
good test-retest reliability and high internal consistency. Factor analysis provided support
for four of the five AQ-Child design subscales. Future studies should evaluate how the
AQ-C performs in population screening
287. Aviel A, Ostfeld E. Acquired irreversible sensorineural hearing loss associated with otitis
media with effusion. Am J Otolaryng 1982;3:217-222.
Ref ID: 584
71
288. Awaad Y, Tayem H, Munoz S, Ham S, Michon AM, Awaad R. Functional assessment
following intrathecal baclofen therapy in children with spastic cerebral palsy. J Child Neurol
2003;18(1):26-34.
Ref ID: 3873
Abstract: The purpose of this article is to describe outcomes of intrathecal baclofen therapy
for 29 patients with cerebral palsy, focusing on impairments, functional limitations, and
disability. Patients received individualized rehabilitation and were followed up to 24 months.
The primary outcome measures were the Ashworth Scale and the functional skills and
caregiver assistance scales of the Pediatric Evaluation of Disability Inventory (PEDI).
Ashworth Scale scores were significantly reduced (P < or = .0005). All areas of functional
skills and caregiver assistance improved. Comparing groups of adults and patients less
than 18 years, there were no significant differences, but there was a relationship between
age and dose. Comparing groups of patients in high and low levels of independent
functional mobility, no significant differences were found. These results provide suggestive
evidence that the combination of intrathecal baclofen therapy and rehabilitation has positive
effects across the dimensions of disablement. This study serves as a basis for high-level
scientific studies of these effects
289. Awadalla P, Gauthier J, Myers RA et al. Direct measure of the de novo mutation rate in
autism and schizophrenia cohorts. Am J Hum Genet 2010;87(3):316-324.
Ref ID: 7012
Abstract: The role of de novo mutations (DNMs) in common diseases remains largely
unknown. Nonetheless, the rate of de novo deleterious mutations and the strength of
selection against de novo mutations are critical to understanding the genetic architecture of
a disease. Discovery of high-impact DNMs requires substantial high-resolution interrogation
of partial or complete genomes of families via resequencing. We hypothesized that
deleterious DNMs may play a role in cases of autism spectrum disorders (ASD) and
schizophrenia (SCZ), two etiologically heterogeneous disorders with significantly reduced
reproductive fitness. We present a direct measure of the de novo mutation rate (mu) and
selective constraints from DNMs estimated from a deep resequencing data set generated
from a large cohort of ASD and SCZ cases (n = 285) and population control individuals (n =
285) with available parental DNA. A survey of approximately 430 Mb of DNA from 401
synapse-expressed genes across all cases and 25 Mb of DNA in controls found 28
candidate DNMs, 13 of which were cell line artifacts. Our calculated direct neutral mutation
rate (1.36 x 10(-8)) is similar to previous indirect estimates, but we observed a significant
excess of potentially deleterious DNMs in ASD and SCZ individuals. Our results emphasize
the importance of DNMs as genetic mechanisms in ASD and SCZ and the limitations of
using DNA from archived cell lines to identify functional variants
290. Axon PR, Temple RH, Saeed SR, Ramsden RT. Cochlear ossification after meningitis. Am
J Otol 1998;19(6):724-729.
Ref ID: 6266
Abstract: OBJECTIVE: This study aimed to assess the pathologic processes that result in
ossification of the cochlear lumen after bacterial meningitis. STUDY DESIGN: The study
design was a retrospective case review. SETTING: The study was conducted at a tertiary
referral center. PATIENTS: Profoundly deaf postmeningitic patients who underwent
cochlear implantation were studied. INTERVENTIONS: Diagnostic and therapeutic
observations were performed. MAIN OUTCOME MEASURES: The extent of cochlear
ossification is classified and related to age at which infection occurred, cerebrospinal fluid
leukocyte count, Gram's stain, organism, and delay between meningitis and implantation.
The extent of ossification noted on high-definition computed tomographic (CT) scan is
compared with surgical findings and related to the time delays between meningitis,
imaging, and surgery. RESULTS: Ossification fell into three groups: gross ossification of
the scala tympani and variable amounts of the scala vestibuli; partial ossification localized
to the basal turn of the scala tympani; and no ossification. There was no correlation
between the extent of ossification and the age when infected, type of pathogen,
72
cerebrospinal fluid leukocyte count, and time delay between meningitis and implantation.
Visualization of bacteria on Gram's stain was a highly sensitive measure of ossification
(0.93) but was not specific (0.6) with positive and negative predictive values of 0.76 and
0.86, respectively. High-definition CT underestimated the extent of ossification in 50% of
cases when performed within 6 months of meningitis. CONCLUSIONS: Ossification is
either gross or localized to the basal turn of the scala tympani. If ossification does occur, it
is rapid and complete within a few months of infection. The visualization of bacteria on
Gram's stain is a sensitive indicator for the presence of ossification but has low specificity.
High-definition CT, if performed within the first 6 months of meningitis, can be an inaccurate
diagnostic tool and therefore should be performed as close to the date of surgery as
possible
291. Aylward EH, Richards TL, Berninger VW et al. Instructional treatment associated with
changes in brain activation in children with dyslexia. Neurology 2003;61(2):212-219.
Ref ID: 7249
Abstract: OBJECTIVE: To assess the effects of reading instruction on fMRI brain activation
in children with dyslexia. BACKGROUND: fMRI differences between dyslexic and control
subjects have most often involved phonologic processing tasks. However, a growing body
of research documents the role of morphologic awareness in reading and reading disability.
METHODS: The authors developed tasks to probe brain activation during phoneme
mapping (assigning sounds to letters) and morpheme mapping (understanding the
relationship of suffixed words to their roots). Ten children with dyslexia and 11 normal
readers performed these tasks during fMRI scanning. Children with dyslexia then
completed 28 hours of comprehensive reading instruction. Scans were repeated on both
dyslexic and control subjects using the same tasks. RESULTS: Before treatment, children
with dyslexia showed less activation than controls in left middle and inferior frontal gyri,
right superior frontal gyrus, left middle and inferior temporal gyri, and bilateral superior
parietal regions for phoneme mapping. Activation was significantly reduced for children with
dyslexia on the initial morpheme mapping scan in left middle frontal gyrus, right superior
parietal, and fusiform/occipital region. Treatment was associated with improved reading
scores and increased brain activation during both tasks, such that quantity and pattern of
activation for children with dyslexia after treatment closely resembled that of controls. The
elimination of group differences at follow-up was due to both increased activation for the
children with dyslexia and decreased activation for controls, presumably reflecting practice
effects. CONCLUSION: These results suggest that behavioral gains from comprehensive
reading instruction are associated with changes in brain function during performance of
language tasks. Furthermore, these brain changes are specific to different language
processes and closely resemble patterns of neural processing characteristic of normal
readers
292. Aylward EH, Minshew NJ, Field K, Sparks BF, Singh N. Effects of age on brain volume and
head circumference in autism. Neurology 2002;59(2):175-183.
Ref ID: 3610
Abstract: OBJECTIVE: To determine whether brain volume, as assessed on MRI scans,
differs between individuals with autism and control subjects, and whether such differences
are affected by age. BACKGROUND: Previous studies have found increased brain weight,
head circumference, and MRI brain volume in children with autism. However, studies of
brain size in adults with autism have yielded conflicting results. The authors hypothesize
that enlargement of the brain may be a feature of brain development during early childhood
in autism that normalizes with maturational processes. METHODS: The authors measured
total brain volumes from 1.5-mm coronal MRI scans in 67 non-mentally retarded children
and adults with autism and 83 healthy community volunteers, ranging in age from 8 to 46
years. Head circumference was also measured. Groups did not differ on age, sex, verbal
IQ, or socioeconomic status. RESULTS: Brain volumes were significantly larger for children
with autism 12 years old and younger compared with normally developing children, when
controlling for height. Brain volumes for individuals older than age 12 did not differ between
73
the autism and control groups. Head circumference was increased in both younger and
older groups of subjects with autism, suggesting that those subjects older than age 12 had
increased brain volumes as children. CONCLUSIONS: Brain development in autism follows
an abnormal pattern, with accelerated growth in early life that results in brain enlargement
in childhood. Brain volume in adolescents and adults with autism is, however, normal, and
appears to be due to a slight decrease in brain volume for these individuals at the same
time that normal children are experiencing a slight increase
293. Aylward EH, Reiss AL, Reader MJ, Singer HS, Brown JE, Denckla MB. Basal ganglia
volumes in children with attention-deficit hyperactivity disorder. J Child Neurol
1996;11(2):112-115.
Ref ID: 2375
Abstract: Previous research has demonstrated volume reduction of the left globus pallidus
in children with the codiagnoses of Tourette syndrome and attention-deficit hyperactivity
disorder (ADHD), in comparison with children who have Tourette syndrome alone and with
normal controls. The purpose of this study was to determine whether children with ADHD
alone also had volume reduction of the globus pallidus or other basal ganglia structures.
Subjects were 10 boys with ADHD, 16 boys with Tourette syndrome and ADHD, and 11
normal control boys. Groups were matched for age. Boys with ADHD were individually
matched for age, handedness, and IQ to 10 of the 16 boys with Tourette syndrome and
ADHD. Volumes of caudate, putamen, and globus pallidus were measured and corrected
for brain volume. The boys with ADHD had significantly smaller left globus pallidus volume
and total globus pallidus volume (corrected for brain volume) than the normal controls. The
Tourette syndrome plus ADHD group did not differ from the ADHD group on any of the
measures. We conclude that small globus pallidus volume, particularly on the left side, is
associated with ADHD
294. Ayres AJ, Tickle LS. Hyper-responsivity to touch and vestibular stimuli as a predictor of
positive response to sensory integration procedures by autistic children. Am J Occup Ther
1980;34(6):375-381.
Ref ID: 4686
Abstract: Sensory processing disturbance in autistic children as a predictor of response to
sensory integrative procedures was investigated. Ten autistic children, ages 3-1/2 to 13
years (mean, 7.4 years), were initially evaluated in regard to their hypo-, hyper-, or normal
responsivity to visual, auditory, tactile, vestibular, proprioceptive, olfactory, and gustatory
stimuli. After evaluation, each child received therapy that provided somatosensory and
vestibular stimulation and elicited adaptive responses to these stimuli. At the end of one
year of therapy, each child's progress was judged in relationship to that of the others, and
the group was divided into the six best and the four poorest respondents. Stepwise
discriminant analysis identified which initial test variables predicted good or poor responses
to therapy. The good respondents showed tactile defensiveness, avoidance of movement,
gravitational insecurity, and an orienting response to an air puff. Results suggest that
children who registered sensory input but failed to modulate it responded better to therapy
than those who were hypo-responsive or failed to orient to sensory input
295. Baas D, Legrand C, Samarut J, Flamant F. Persistence of oligodendrocyte precursor cells
and altered myelination in optic nerve associated to retina degeneration in mice devoid of
all thyroid hormone receptors. Proc Natl Acad Sci U S A 2002;99(5):2907-2911.
Ref ID: 6254
Abstract: Thyroid hormone (3,5,3'-triiodo-l-thyronine or T3) exerts a pleiotropic activity
during central nervous system development. Hypothyroidism during the fetal and postnatal
life results in an irreversible mental retardation syndrome. At the cellular level, T3 is known
to act on neuronal and glial lineages and to control cell proliferation, apoptosis, migration,
and differentiation. Oligodendrocyte precursor cells (OPC) found at birth in the optic nerves
are self-renewing cells that normally differentiate during the first 3 weeks of rodent
postnatal life into postmitotic myelinating oligodendrocytes. In vitro, the addition of T3 to
74
OPC is sufficient to trigger their terminal differentiation. The present analysis of T3 receptor
knockout mice reveals that the absence of all T3 receptor results in the persistence of OPC
proliferation in adult optic nerves, in a default in myelination, and sometimes in the
degeneration of the retinal ganglion neurons. Thus, T3 signaling is necessary in vivo to
promote the complete differentiation of OPC
296. Babb A, Carlson WO. Idiopathic toe-walking. S D Med 2008;61(2):53, 55-53, 57.
Ref ID: 5648
Abstract: Idiopathic toe-walking is a diagnosis of exclusion when a child presents with
bilateral toe-to-toe gait. Although toe-walking is considered part of the normal gait spectrum
in development, it is abnormal when persisting past the age of two. Toe-walking may be
caused by cerebral palsy, congenital contracture of the Achilles tendon or paralytic
muscular disorders such as Duchenne Muscular Dystrophy. Idiopathic toe-walking may be
associated with developmental disorders such as autism or other myopathic or neuropathic
disorders. The majority of disorders causing toe-walking can be ruled out through the
history and physical examination, resulting in a diagnosis of idiopathic toe-walking.
However, it may be difficult to differentiate mild forms of cerebral palsy, specifically mild
spastic diplegia, and idiopathic toe-walking. The treatment options for idiopathic toe-walking
include observation, conservative methods and surgical methods. Most children can be
treated in the primary care setting with either observation or conservative treatment.
Patients with severe contracture of the Achilles tendon, or persistent toe-walking, may need
surgical intervention. The prognosis of idiopathic toe-walking is favorable with both
conservative and surgical treatment allowing children to attain normal function and range of
plantarflexion. The following article provides an overview of the background information,
differential diagnosis and treatment options for idiopathic toe-walking
297. Bach S, Brandeis D, Hofstetter C, Martin E, Richardson U, Brem S. Early emergence of
deviant frontal fMRI activity for phonological processes in poor beginning readers
63. Neuroimage 2010;53(2):682-693.
Ref ID: 7361
Abstract: Phonological awareness refers to the ability to perceive and manipulate the sound
structure of language and is especially important when children learn to read. Poor
phonological awareness is considered the major cause for the emergence of reading
difficulties. In this functional magnetic resonance imaging (fMRI) study, we examined the
brain correlates of phonological processing in young beginning readers (aged 8.3+/-0.4 y,
2nd grade) with poor (<25th percentile) or normal, age-appropriate reading skills (>40th
percentile) using a covert reading and mental letter substitution task. Letter substitution in
words and nonwords induced pronounced activity in a left frontal language network related
to phonological processing, with maxima in the left inferior frontal gyrus and in the insula.
The activation within this frontal network increased with better reading skills and
differentiated between normal and poor reading young children. Lateralization indices of
overall frontal activity for normal and poor readers pointed to stronger left hemispheric
involvement in normal readers as compared to the more bilateral activation pattern in poor
readers. To summarize, young children with age-appropriate reading skills display a left
hemispheric dominance characteristic for language processing already by grade two. The
more bilateral activation pattern in poor readers points to an increased effort and the
emergence of compensatory strategies for reading and phonological processing just 1.5
years after the start of formal reading instruction
298. Bachara GH, Phelan WJ. Rhythmic movement in deaf children. Percept Motor Skills
1980;50:933-934.
Ref ID: 2686
299. Bachevalier J, Merjanian PM. The contribution of medial temporal lobe structures in
infantile autism: A neurobehavioral study in primates. In: Bauman ML, Kemper TL, editors.
75
The Neurobiology of Autism. Baltimore: Johns Hopkins University Press; 1994:146-169.
Ref ID: 308
300. Bachevalier J. Medial temporal lobe structures and autism: A review of clinical and
experimental findings. Neuropsychologia 1994;32(6):627-648.
Ref ID: 2125
301. Bacon AL, Fein D, Morris R, Waterhouse L, Allen DA. The responses of autistic children to
the distress of others. J Autism Dev Disord 1998;28(2):129-142.
Ref ID: 2159
302. Badcock C, Crespi B. Battle of the sexes may set the brain. Nature
2008;454(7208):1054-1055.
Ref ID: 6502
Abstract: none
303. Badcock NA, Bishop DV, Hardiman MJ, Barry JG, Watkins KE. Co-localisation of abnormal
brain structure and function in specific language impairment. Brain Lang
2012;120(3):310-320.
Ref ID: 7296
Abstract: We assessed the relationship between brain structure and function in 10
individuals with specific language impairment (SLI), compared to six unaffected siblings,
and 16 unrelated control participants with typical language. Voxel-based morphometry
indicated that grey matter in the SLI group, relative to controls, was increased in the left
inferior frontal cortex and decreased in the right caudate nucleus and superior temporal
cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate
nucleus relative to controls. In an auditory covert naming task, the SLI group showed
reduced activation in the left inferior frontal cortex, right putamen, and in the superior
temporal cortex bilaterally. Despite spatially coincident structural and functional
abnormalities in frontal and temporal areas, the relationships between structure and
function in these regions were different. These findings suggest multiple structural and
functional abnormalities in SLI that are differently associated with receptive and expressive
language processing
304. Badgaiyan RD, Posner MI. Mapping the cingulate cortex in response selection and
monitoring. NeuroImage 1998;7(3):255-260.
Ref ID: 2299
Abstract: Many cognitive tasks have activated areas of the cingulate cortex. These include
error detection, divided attention, conflict, and word generation tasks. However, the exact
area of the cingulate found to be active has differed. This could be due to difference in
subjects, laboratories, data analysis, or task conditions. The current study uses two very
different tasks known to activate the cingulate and compares data from the same subjects
and same trials to see whether there are temporal and spatial distinctions in cingulate
activations. The tasks chosen were generation of the use of a noun and feedback that an
error was made in the time window required for generation. High-density electrical
recording was used to trace the time course of cingulate activation in the difference waves
between correct and error feedback and between generate and repeat. Both tasks
produced activity that is consistent with cingulate activation. However, the two tasks
produced activity in different areas. These data are consistent with the idea that differences
in areas of the cingulate activated differ between cognitive tasks and are not merely due to
subject and laboratory differences
305. Bae SY, Gon LC, Min KJ et al. Clinical and genetic spectrum of 18 unrelated Korean
patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel
NSD1 mutations. J Hum Genet 2012.
Ref ID: 7420
76
Abstract: Sotos syndrome is an overgrowth syndrome with characteristic facial
dysmorphism, variable severity of learning disabilities and macrocephaly with overgrowth.
Haploinsufficiency of the nuclear receptor SET domain-containing protein 1 (NSD1) gene
located on 5q35 has been implicated as the cause of Sotos syndrome. This study was
performed to investigate the mutation spectrum of NSD1 abnormalities and meaningful
genotype-phenotype correlations in Korean patients with Sotos syndrome. Eighteen
unrelated Korean patients with Sotos syndrome were enrolled for clinical and molecular
analyses. Cytogenetic studies were performed to confirm 5q35 microdeletion, and NSD1
sequencing analysis was performed to identify intragenic mutations. NSD1 abnormalities
were identified in 15 (83%) patients. Among them, eight patients (53%) had 5q35
microdeletions and the other seven patients (47%) had seven different NSD1 intragenic
mutations including four novel mutations. The mutation spectrum of Korean patients with
Sotos syndrome was similar to that of previous studies for Japanese patients. Height was
significantly shorter and age of walking alone was significantly older in the microdeletion
group compared with those in the intragenic mutation group. No significant differences
were observed for other clinical characteristics between the microdeletion and intragenic
mutation groups. Further studies with a larger number of patients will be necessary to draw
conclusive genotype-phenotype correlations.Journal of Human Genetics advance online
publication, 29 November 2012; doi:10.1038/jhg.2012.135
306. Baghdadli A, Pascal C, Grisi S, Aussilloux C. Risk factors for self-injurious behaviours
among 222 young children with autistic disorders. J Intellect Disabil Res 2003;47(Pt
8):622-627.
Ref ID: 4813
Abstract: The aim of this study was to identify risk factors for self-injurious behaviours
(SIBs) in children with autistic disorders. The occurrence of SIB was examined in
comparison with the following variables: chronological age, sex, adaptive skills, speech
level, associated medical condition, degree of autism and parental social class. The
subjects were 222 children aged under 7 years and all of them fulfilled the ICD-10 criteria
for infantile autism. Retrospective data were collected on demographic characteristics and
medical condition. Children were assessed in terms of speech, degree of autism and
adaptive skills in communication, socialization and daily living skills domains. Results
indicated that 50% of the children experienced SIB and 14.6% had severe SIBs. Lower
chronological age, associated perinatal condition, a higher degree of autism and a higher
daily living skills delay were risk factors of SIBs but parental class, sex and epilepsy were
not
307. Bagley C, McGeein V. The taxonomy and course of childhood autism. Percept Motor Skills
1989;69:1264-1266.
Ref ID: 42
308. Bahmad F, O'Malley J, Tranebjaerg L, Merchant SN. Histopathology of nonsyndromic
autosomal dominant midfrequency sensorineural hearing loss. Otol Neurotol
2008;29(5):601-606.
Ref ID: 6189
Abstract: BACKGROUND: Autosomal dominant, nonsyndromic, midfrequency
sensorineural hearing loss (SNHL) is a well-known clinical entity. There are no reported
histopathologic studies of temporal bones from individuals with such a hearing loss.
OBJECTIVES: To describe the otopathology in 2 affected individuals from 2 different
kindreds with nonsyndromic, dominant, midfrequency SNHL. MATERIAL AND METHODS:
Both subjects belonged to multigenerational families with nonsyndromic, autosomal
dominant SNHL showing a cookie-bite pattern. Temporal bones were removed at autopsy
and studied by light microscopy. Cytocochleograms were constructed for hair cells, stria
vascularis, and cochlear neuronal cells. RESULTS: Subject 1 (a 77-yr-old man) from
Kindred A was diagnosed in early childhood with an SNHL that was progressive, reaching
profound levels by adulthood. Both cochleae showed complete loss of inner and outer hair
77
cells, moderate to severe diffuse atrophy of the stria vascularis, and severe loss of cochlear
neurons, including the peripheral dendrites. The hearing loss in Subject 2 (an 82-yr-old
man from Kindred B) began in late childhood, was slowly progressive, and involved the
higher frequencies later in life. Histopathology showed loss of outer and inner hair cells in
the basal turn of the cochlea, moderate to severe loss of stria vascularis, but relative
preservation of peripheral dendrites and cochlear neurons. CONCLUSION: The main
histopathologic abnormalities were loss of hair cells, stria vascularis, and cochlear neurons
in 1 case and loss of hair cells and stria vascularis in the second case. Our results are
consistent with the hypothesis that dysfunction and loss of hair cells may have been the
primary histopathologic correlate for the midfrequency hearing losses in these 2 subjects
309. Bahmad F, Jr., Merchant SN, Nadol JB, Jr., Tranebjaerg L. Otopathology in
Mohr-Tranebjaerg syndrome. Laryngoscope 2007;117(7):1202-1208.
Ref ID: 6144
Abstract: BACKGROUND: Mohr-Tranebjaerg syndrome (MTS) is an X-linked, recessive,
syndromic sensorineural hearing loss (HL) characterized by onset of deafness in childhood
followed later in adult life by progressive neural degeneration affecting the brain and optic
nerves. MTS is caused by mutations in the DDP/TIMM8A gene, which encodes for a 97
amino acid polypeptide; this polypeptide is a translocase of the inner mitochondrial
membrane. OBJECTIVES: To describe the otologic presentation and temporal bone
histopathology in four affected individuals with MTS. MATERIAL AND METHODS: All four
subjects belonged to a large, multigenerational Norwegian family and were known to carry
a frame shift mutation in the TIMM8A gene. Temporal bones were removed at autopsy and
studied by light microscopy. Cytocochleograms were constructed for hair cells, stria
vascularis, and cochlear neuronal cells. Vestibular neurons were also counted. RESULTS:
All four subjects developed progressive HL in early childhood, becoming profoundly deaf by
the age of 10 years. All four developed language, and at least one subject used
amplification in early life. Audiometric evaluation in two subjects showed 80- to 100-dB HL
by the age of 10 years. The subjects died between the ages of 49 and 67. The
otopathology was strikingly similar in that all bones examined showed near-total loss of
cochlear neuronal cells and severe loss of vestibular neurons. When compared with
age-matched controls, there was 90% to 95% loss of cochlear neurons and 75% to 85%
loss of vestibular neurons. CONCLUSIONS: We infer that the HL in MTS is likely to be the
result of a postnatal and progressive degeneration of cochlear neurons and that MTS
constitutes a true auditory neuropathy. Our findings have implications for clinical diagnosis
of patients with MTS and management of the HL
310. Bailey A, Luthert P, Dean A et al. A clinicopathological study of autism. Brain
1998;121(5):889-905.
Ref ID: 2100
311. Bailey A, Palferman S, Heavey L, Le Couteur A. Autism: the phenotypes in relatives. J
Autism Dev Disord 1998;28(5):369-392.
Ref ID: 2142
312. Bailey A, Phillips W, Rutter M. Autism: Towards an integration of clinical, genetic,
neuropsychological, and neurobiological perspectives. J Child Psychol Psychiatry
1996;37(1):89-126.
Ref ID: 1578
313. Bailey A, Le Couteur A, Gottesman I et al. Autism as a strongly genetic disorder: Evidence
from a British twin study. Psychol Med 1995;1:63-77.
Ref ID: 425
Abstract: Two previous epidemiological studies of autistic twins suggested that autism was
predominantly genetically determined, although the findings with regard to a broader
phenotype of cognitive, and possibly social, abnormalities were contradictory. Obstetric and
78
perinatal hazards were also invoked as environmentally determined aetiological factors.
The first British twin sample has been re-examined and a second total population sample of
autistic twins recruited. In the combined sample 60% of monozygotic (MZ) pairs were
concordant for autism versus no dizygotic (DZ) pairs; 92% of MZ pairs were concordant for
a broader spectrum of related cognitive or social abnormalities versus 10% of DZ pairs.
The findings indicate that autism is under a high degree of genetic control and suggest the
involvement of multiple genetic loci. Obstetric hazards usually appear to be consequences
of genetically influenced abnormal development, rather than independent aetiological
factors. Few new cases had possible medical aetiologies, refuting claims that recognized
disorders are common aetiological influences
314. Bailey A, Bolton P, Butler L et al. Prevalence of the fragile-X anomaly amongst twins and
singletons. J Child Psychol Psychiatry 1993;34(5):673-678.
Ref ID: 1345
315. Bailey A, Luthert P, Bolton P, Le Couteur A, Rutter M, Harding B. Autism and
megalencephaly. Lancet 1993;341:1225-1226.
Ref ID: 1571
316. Bailey AJ. Postmortem studies of autism. Autism Res 2008;1(5):265.
Ref ID: 6649
317. Bailey DBJ, Hatton DD, Skinner M, Mesibov G. Autistic behavior, FMR1 protein, and
developmental trajectories in young males. J Autism Dev Disord 2001;31(2):165-174.
Ref ID: 3385
318. Bailey DBJ, Hatton DD, Skinner M. Early developmental trajectories of males with fragile X
syndrome. Am J Ment Retard 1998;103(1):29-39.
Ref ID: 2818
Abstract: Findings from a prospective longitudinal study of 46 boys with fragile X syndrome
between the ages of 24 and 72 months were reported. Hierarchical linear modeling was
used to construct and evaluate overall developmental trajectories and scores in five
domains: Cognition, Communication, Adaptive, Motor, and Personal-Social. The children
varied widely, with significant differences across individuals in both mean rate and level of
performance. Overall development was significantly delayed, with a slope of
.48--approximately half the rate expected for typically developing children. No differences
were found in rates of growth across the five domains. Significant differences were found,
however, in mean levels of performance. At every age tested, Motor and Adaptive scores
were higher than Communication and Cognitive
319. Bailey P. The past, present and future of neurology in the United States. Neurology
2011;76(1):18-22.
Ref ID: 6815
320. Bailey P, Buchanan DN, Bucy PC. Intracranial tumors of infancy and childhood. Chicago,
IL: University ofg Chicago Press; 1939.
Ref ID: 6799
321. Bailine SH, Petraviciute S. Catatonia in autistic twins: role of electroconvulsive therapy. J
ECT 2007;23(1):21-22.
Ref ID: 5122
Abstract: Autism and Asperger disorder are pervasive developmental disorders that impair
social interactions and communications. They are characterized by repetitive and
stereotyped behaviors. Catatonia, a syndrome which is most often associated with
schizophrenia and affective disorders, is seen in up to 6% of patients with autistic spectrum
disorders and in 12% to 17% of adolescents with these disorders. Catatonic symptoms in
79
these cases have been responsive to treatment with electroconvulsive therapy. We report a
case of adolescent identical twins with PDD/Asperger disorder who exhibited catatonia and
were successfully treated with electroconvulsive therapy
322. Baird G, Pickles A, Simonoff E et al. Measles vaccination and antibody response in autism
spectrum disorders. Arch Dis Child 2008.
Ref ID: 5500
Abstract: OBJECTIVE: To test the hypothesis that measles vaccination was involved in the
pathogenesis of ASD as evidenced by signs of a persistent measles infection or abnormally
persistent immune response shown by circulating measles virus or raised antibody titres in
MMR vaccinated children with ASD compared with controls . DESIGN: Case-control study
community based METHODS: A community sample of vaccinated children aged 10-12
years in the UK with ASD (N=98) and two control groups of similar age, one with special
educational needs but no ASD (N=52) and one typically developing group (N=90), were
tested for measles virus and antibody response to measles in serum. RESULTS: No
difference was found between cases and controls for measles antibody response. There
was no dose response relationship between autism symptoms and antibody levels.
Measles virus nucleic acid was amplified by RT-PCR in PMBC from one case with autism
and two typically developing children. There was no evidence of a differential response to
measles virus or the measles component of the MMR in children with ASD, with or without
regression, and controls who had either one or two doses of MMR. Only one child from the
control group had clinical symptoms of a possible enterocolitis
323. Baird G, Simonoff E, Pickles A et al. Prevalence of disorders of the autism spectrum in a
population cohort of children in South Thames: the Special Needs and Autism Project
(SNAP). Lancet 2006;368(9531):210-215.
Ref ID: 5274
Abstract: BACKGROUND: Recent reports have suggested that the prevalence of autism
and related spectrum disorders (ASDs) is substantially higher than previously recognised.
We sought to quantify prevalence of ASDs in children in South Thames, UK. METHODS:
Within a total population cohort of 56 946 children aged 9-10 years, we screened all those
with a current clinical diagnosis of ASD (n=255) or those judged to be at risk for being an
undetected case (n=1515). A stratified subsample (n=255) received a comprehensive
diagnostic assessment, including standardised clinical observation, and parent interview
assessments of autistic symptoms, language, and intelligence quotient (IQ). Clinical
consensus diagnoses of childhood autism and other ASDs were derived. We used a
sample weighting procedure to estimate prevalence. FINDINGS: The prevalence of
childhood autism was 38.9 per 10,000 (95% CI 29.9-47.8) and that of other ASDs was 77.2
per 10,000 (52.1-102.3), making the total prevalence of all ASDs 116.1 per 10,000
(90.4-141.8). A narrower definition of childhood autism, which combined clinical consensus
with instrument criteria for past and current presentation, provided a prevalence of 24.8 per
10,000 (17.6-32.0). The rate of previous local identification was lowest for children of less
educated parents. INTERPRETATION: Prevalence of autism and related ASDs is
substantially greater than previously recognised. Whether the increase is due to better
ascertainment, broadening diagnostic criteria, or increased incidence is unclear. Services in
health, education, and social care will need to recognise the needs of children with some
form of ASD, who constitute 1% of the child population
324. Baird G, Robinson RO, Boyd S, Charman T. Sleep electroencephalograms in young
children with autism with and without regression. Dev Med Child Neurol
2006;48(7):604-608.
Ref ID: 5275
Abstract: A link has been postulated between regressive autism and the spectrum of
epileptic encephalopathic conditions including Landau-Kleffner syndrome with the
suggestion that subclinical epilepsy may be causative of regression in autism. This is an
audit of investigation using sleep electroencephalograms (EEG) in 64 children (56 males, 8
80
females; mean age 35.6mo [SD 8.2mo]; range 18-48mo) with autism. No child had a
history suggestive of epilepsy. Thirty-nine of the children presented with regressive autism
and 20 of the participants showed some epileptiform abnormality. There was no significant
difference in epileptiform activities in those who showed regression compared with those
who did not. No child showed electrical status epilepticus with continuous spike-wave
discharges in slow sleep. There was no evidence that these cases of autism with and
without regression were associated with epileptic encephalopathy. The significance of
epileptiform discharges without epilepsy in the sleep EEG in autism remains unknown
325. Baird G, Cass H, Slonims V. Diagnosis of autism. BMJ 2003;327(7413):488-493.
Ref ID: 5516
326. Baird G, Charman T, Baron-Cohen S et al. A screening instrument for autism at 18 months
of age: a 6-year follow- up study. J Am Acad Child Adolesc Psychiatry 2000;39(6):694-702.
Ref ID: 3160
Abstract: OBJECTIVES: A population of 16,235 children aged 18 months was screened
using the Checklist for Autism in Toddlers (CHAT) to identify childhood autism (CA). Two
further screening procedures were conducted at age 3 and 5 years. The population was
followed up at age 7 years in order to establish the sensitivity, specificity, and positive
predictive value of the instrument. METHOD: A brief checklist assessing joint attention and
pretend play behaviors was administered by primary health care practitioners when the
children were 18 months old. Follow-up methods included screening through parents and
health practitioners and checking medical and educational records. RESULTS: Nineteen
cases of CA were successfully identified by the CHAT at 18 months. At follow-up a total of
50 cases of CA were identified via all surveillance methods. Thus, the CHAT has a
sensitivity of 38% and a specificity of 98% for identifying CA. The positive predictive value
of the instrument was maximized by concentration on the highest-risk group. Repeated
screening 1 month later increased the positive predictive value to 75% for identification of
CA but reduced the sensitivity to 20%, although the specificity was close to 100%. The
screen also identified cases of pervasive developmental disorder as well as children with
language and other developmental disorders. CONCLUSIONS: The CHAT can be used to
identify cases of autism and related pervasive developmental disorders at 18 months of
age. It is emphasized that the CHAT is not a diagnostic instrument but can identify potential
cases of autism spectrum disorders for a full diagnostic assessment
327. Baker L, Cantwell DP. A prospective psychiatric follow-up of children with speech/language
disorders. J Am Acad Child Adolesc Psychiatry 1987;26:546-553.
Ref ID: 1308
328. Baker M, Mackenzie IR, Pickering-Brown SM et al. Mutations in progranulin cause
tau-negative frontotemporal dementia linked to chromosome 17. Nature
2006;442(7105):916-919.
Ref ID: 5871
Abstract: Frontotemporal dementia (FTD) is the second most common cause of dementia
in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a
family history of dementia, consistent with a strong genetic component to the disease. In
1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were
shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17).
The neuropathology of patients with defined MAPT mutations is characterized by
cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in
multiple FTD families with significant evidence for linkage to the same region on
chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and
the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these
patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and
characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we
demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that
81
are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on
chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the
regulation of multiple processes including development, wound repair and inflammation.
PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is
increased in activated microglia in many neurodegenerative diseases including
Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results
identify mutations in PGRN as a cause of neurodegenerative disease and indicate the
importance of PGRN function for neuronal survival
329. Balconi M. Dorsolateral prefrontal cortex, working memory and episodic memory
processes: insight through transcranial magnetic stimulation techniques. Neurosci Bull
2013.
Ref ID: 7470
Abstract: The ability to recall and recognize facts we experienced in the past is based on a
complex mechanism in which several cerebral regions are implicated. Neuroimaging and
lesion studies agree in identifying the frontal lobe as a crucial structure for memory
processes, and in particular for working memory and episodic memory and their
relationships. Furthermore, with the introduction of transcranial magnetic stimulation (TMS)
a new way was proposed to investigate the relationships between brain correlates, memory
functions and behavior. The aim of this review is to present the main findings that have
emerged from experiments which used the TMS technique for memory analysis. They
mainly focused on the role of the dorsolateral prefrontal cortex in memory process.
Furthermore, we present state-of-the-art evidence supporting a possible use of TMS in the
clinic. Specifically we focus on the treatment of memory deficits in depression and anxiety
disorders
330. Balconi M, Pozzoli U. Event-related oscillations (ERO) and event-related potentials (ERP)
in emotional face recognition. Int J Neurosci 2008;118(10):1412-1424.
Ref ID: 7471
Abstract: The study aims to explore the significance of event-related potentials (ERPs) and
event-related brain oscillations (EROs) (delta, theta, and alpha power) in response to
emotional face during 180-250 poststimulus time interval. Twenty-one adults looked at
emotional (sad, happy, fearful) or neutral faces. The results demonstrated that the
emotional face elicited a negative peak at approximately 230 ms (N230). Moreover EEG
measures showed that motivational significance of face (stimulus type) can modulate the
amplitude of EEG, especially for theta and delta. Regression analysis showed that theta
oscillations mainly effect as oscillation activity at the N2 latency. Thus, this frequency band
variation could represent a complex set of cognitive processes, whereby selective attention
becomes focused on an emotional relevant stimulus
331. Balderas I, Rodriguez-Ortiz CJ, Salgado-Tonda P, Chavez-Hurtado J, McGaugh JL,
Bermudez-Rattoni F. The consolidation of object and context recognition memory involve
different regions of the temporal lobe. Learn Mem 2008;15(9):618-624.
Ref ID: 6766
Abstract: These experiments investigated the involvement of several temporal lobe regions
in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was
infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of
rats immediately after the sample phase of object or object-in-context recognition memory
training. Anisomycin infused into perirhinal or insular cortices blocked long-term (24 h), but
not short-term (90 min) object recognition memory. Infusions into the hippocampus or
amygdala did not impair object recognition memory. Anisomycin infused into the
hippocampus blocked long-term, but not short-term object-in-context recognition memory,
whereas infusions administered into the perirhinal cortex, insular cortex, or amygdala did
not affect object-in-context recognition memory. These results clearly indicate that distinct
regions of the temporal lobe are differentially involved in long-term object and
object-in-context recognition memory. Whereas perirhinal and insular cortices are required
82
for consolidation of familiar objects, the hippocampus is necessary for consolidation of
contextual information of recognition memory. Altogether, these results suggest that
temporal lobe structures are differentially involved in recognition memory consolidation
332. Bali B, Kull LL, Strug LJ et al. Autosomal dominant inheritance of centrotemporal sharp
waves in rolandic epilepsy families. Epilepsia 2007;48(12):2266-2272.
Ref ID: 6854
Abstract: PURPOSE: Centrotemporal sharp (CTS) waves, the electroencephalogram
(EEG) hallmark of rolandic epilepsy, are found in approximately 4% of the childhood
population. The inheritance of CTS is presumed autosomal dominant but this is
controversial. Previous studies have varied considerably in methodology, especially in the
control of bias and confounding. We aimed to test the hypothesis of autosomal dominant
inheritance of CTS in a well-designed family segregation analysis study. METHODS:
Probands with rolandic epilepsy were collected through unambiguous single ascertainment.
Siblings in the age range 4-16 years underwent sleep-deprived EEG; observations from
those who remained awake were omitted. CTS were rated as present or absent by two
independent observers blinded to the study hypothesis and subject identities. We
computed the segregation ratio of CTS, corrected for ascertainment. We tested the
segregation ratio estimate for consistency with dominant and recessive modes of
inheritance, and compared the observed sex ratio of those affected with CTS for
consistency with sex linkage. RESULTS: Thirty siblings from 23 families underwent EEG
examination. Twenty-three showed evidence of sleep in their EEG recordings. Eleven of 23
recordings demonstrated CTS, yielding a corrected segregation ratio of 0.48 (95% CI:
0.27-0.69). The male to female ratio of CTS affectedness was approximately equal.
CONCLUSIONS: The segregation ratio of CTS in rolandic epilepsy families is consistent
with a highly penetrant autosomal dominant inheritance, with equal sex ratio. Autosomal
recessive and X-linked inheritance are rejected. The CTS locus might act in combination
with one or more loci to produce the phenotype of rolandic epilepsy
333. Balkany TJ. The cochlear implant. Otolaryng Clin N Am 1986;19:1.
Ref ID: 1793
334. Ballaban-Gil K, Tuchman R. Epilepsy and epileptiform EEG: association with autism and
language disorders. MRDDRR 2000;6(4):300-308.
Ref ID: 3296
Abstract: The relationship between epilepsy, language, behavior, and cognition is not well
understood. Developmental and acquired disabilities such as autistic spectrum disorders,
Landau-Kleffner Syndrome, electrical status epilepticus in sleep, and developmental
dysphasias have been associated with epileptiform abnormalities. These disorders share
many common features and raise important questions regarding this intricate relationship.
This article reviews these disorders and discusses the proposed interaction between
epileptiform abnormalities and cognitive dysfunciton. Diagnostic and treatment issues will
also be reviewed.
335. Ballaban-Gil K, Rapin I, Tuchman RF, Shinnar S. Longitudinal examination of the
behavioral, language, and social changes in a population of adolescents and young adults
with autistic disorder. Pediat Neurol 1996;15:217-223.
Ref ID: 906
Abstract: This follow-up study evaluates the behavioral, language, and social outcomes in a
population of autistic patients initially examined in childhood. We evaluated 102 (63%) of
the 163 eligible subjects, including 54 adolescents (12-17 years of age) and 45 adults (> or
= 18 years of age). Three patients had died in the interim. Behavior difficulties continued to
be a problem in 69% of adolescents and adults. Thirty-five percent of adolescents and 49%
of adults engaged in self-injurious behavior, and slightly more than 50% of adolescents and
adults exhibited some stereotypic behaviors. Over 90% of both adolescents and adults had
persisting social deficits. Language improved with age, although only 35% achieved normal
83
or near-normal fluency. Comprehension also improved, although only 29% of subjects had
achieved normal or near-normal comprehension of oral language. At the time of last
follow-up, 28% of all patients and 53% of adults were living in residential placement. Only
11% of adults were employed on the open market, all in menial jobs; an additional 16%
were employed in sheltered workshops. The social, behavioral, and language deficits
identified in early life in autistic children tend to persist into adolescence and young
adulthood
336. Ballaban-Gil K, Rapin I, Tuchman RF, Freeman K, Shinnar S. The risk of seizures in
autistic individuals: Occurrence of a secondary peak in adolescence. Epilepsia Suppl. 3,
84. 1993.
Ref Type: Abstract
Ref ID: 277
337. Ballantyne AO, Spilkin AM, Hesselink J, Trauner DA. Plasticity in the developing brain:
intellectual, language and academic functions in children with ischaemic perinatal stroke.
Brain 2008;131(Pt 11):2975-2985.
Ref ID: 5978
Abstract: The developing brain has the capacity for a great deal of plasticity. A number of
investigators have demonstrated that intellectual and language skills may be in the normal
range in children following unilateral perinatal stroke. Questions have been raised,
however, about whether these skills can be maintained at the same level as the brain
matures. This study aimed to examine the stability of intellectual, academic and language
functioning during development in children with perinatal stroke, and to resolve the
inconsistencies raised in previous studies. Participants were 29 pre-school to school-age
children with documented unilateral ischaemic perinatal stroke and 24 controls.
Longitudinal testing of intellectual and cognitive abilities was conducted at two time points.
Study 1 examined IQ, academic skills and language functions using the same test version
over the test-retest interval. Study 2 examined IQ over a longer test-retest interval
(pre-school to school-age), and utilized different test versions. This study has resulted in
important new findings. There is no evidence of decline in cognitive function over time in
children with perinatal unilateral brain damage. These results indicate that there is sufficient
ongoing plasticity in the developing brain following early focal damage to result in the
stability of cognitive functions over time. Also, the presence of seizures limits plasticity such
that there is not only significantly lower performance on intellectual and language measures
in the seizure group (Study 1), but the course of cognitive development is significantly
altered (as shown in Study 2). This study provides information to support the notion of
functional plasticity in the developing brain; yields much-needed clarification in the literature
of prognosis in children with early ischaemic perinatal stroke; provides evidence that
seizures limit plasticity during development; and avoids many of the confounds in prior
studies. A greater understanding of how children with ischaemic perinatal stroke fare over
time is particularly important, as there has been conflicting information regarding prognosis
for this population. It appears that when damage is sustained very early in brain
development, cerebral functional reorganization acts to sustain a stable rate of
development over time
338. Ballantyne AO, Spilkin AM, Trauner DA. Language outcome after perinatal stroke: does
side matter? Child Neuropsychol 2007;13(6):494-509.
Ref ID: 5983
Abstract: The goal of this study was to examine structured language skills in children with
perinatal strokes. Participants were 28 school-age children with early focal brain lesions (17
with left hemisphere [LH] damage, 11 with right hemisphere [RH] damage), and 57
controls. A standardized test of language (Clinical Evaluation of Language
Fundamentals-Revised) was administered. Receptive, Expressive, and Total Language
scores, as well as subtest scores, were analyzed. Control participants scored within the
normal range, whereas the LH and RH groups scored significantly more poorly than did
84
controls. There were no differences between the LH and RH groups on any of the language
scores, and all scores were below the 14th percentile. Within the lesion group as a whole,
scores were not related to lesion laterality, site, or severity. Results also were not
accounted for by socioeconomic status or IQ. However, children who experienced seizures
demonstrated significantly poorer performance than did children who did not experience
seizures. Damage to either the LH or RH early in development adversely affects later
language abilities, particularly on tasks with structured and complex linguistic demands.
Although lesion side has little effect, the presence or absence of seizures is a major
contributor to language outcome
339. Baloh RW, Honrubia V. Clinical Neurophysiology of the Vestibular System. 2 ed.
Philadelphia PA: P.A. Davis; 1990.
Ref ID: 1758
340. Baloh RW. The Essentials of Neurotology: Dizziness, Hearing Loss and Tinnitus.
Philadelphia: F.A. Davis; 1984.
Ref ID: 792
341. Balsamo LM, Xu B, Grandin CB et al. A functional magnetic resonance imaging study of left
hemisphere language dominance in children. Arch Neurol 2002;59(7):1168-1174.
Ref ID: 4367
Abstract: BACKGROUND: Functional magnetic resonance imaging is a noninvasive
method of assessing language dominance in a pediatric population. OBJECTIVE: To
determine the pattern of receptive language lateralization in healthy children. DESIGN: We
used functional magnetic resonance imaging to assess an auditory language task in 11
children (7 girls, 4 boys; mean age, 8.5 years). Participants alternately rested and listened
to descriptors of nouns presented auditorily, naming the object described silently.
Asymmetry indices ([(left - right)/(left + right)]) were calculated for a priori-determined
regions of interest. RESULTS: The results showed strong activation bilaterally, with greater
activation on the left in the superior and middle temporal gyri. Other areas of activation
included the cuneus, the left inferior temporal gyrus, the prefrontal area, and the left
fusiform and lingual gyri. Regions of interest analysis of individual scans showed additional
activation in the left frontal lobe. Asymmetry indices showed strong left lateralization of the
inferior frontal gyrus, middle frontal gyrus, and the Wernicke region. CONCLUSIONS:
Hemispheric lateralization was clearly demonstrated in 8 children. As in adults, left
hemisphere lateralization of receptive language is present at age 8 years
342. Baltaxe C, Simmons JQ. Prosodic development in normal and autistic children. In: Schopler
E, Mesibov GB, editors. Communication Problems in Autism. New York: Plenum Press;
1985:95-123.
Ref ID: 2
343. Baltaxe C. Acoustic characteristics of prosody in autism. In: Mittler P, editor. Frontiers of
Knowledge in Mental Retardation. Baltimore: University Park Press; 1981.
Ref ID: 692
344. Baltaxe C, Simmons JQ, III. Language patterns of adolescent autistics: a comparison
between English and German. In: Mittler P, editor. Research in practice in mental
retardation: proceedings of the fourth congress of the International Association for the
Scientific Study of Mental Deficiency, Washington, D.C., U.S.A., 22-27 August, 1976, the
American University Vol. 2: Education and training. Baltimore MD: University Park Press;
1977:267-278.
Ref ID: 5011
345. Baltaxe CAM, Simmons JQ, III. A comparison of language issues in high-functioning autism
and related disorders with onset in childhood and adolescence. In: Schopler E, Mesibov
85
GB, editors. High-Functioning Individuals with Autism. New York: Plenum Press;
1991:201-225.
Ref ID: 352
346. Baltaxe CAM. Pragmatic deficits in the language of autistic adolescents. J Ped Psychol
1977;2:176-180.
Ref ID: 690
347. Baltaxe CAM, Simmons JQI. Language in childhood psychosis: A review. J Speech Hear
Disord 1975;40:439-458.
Ref ID: 1306
Abstract: Childhood psychosis is a group of disorders characterized by numerous
behavioral abnormalities, the most significant of which may well be in the area of language.
Absence, delay, or deficit in linguistic development are frequently contributing factors to the
retardation often associated with childhood psychosis. The literature on language in
childhood psychosis covering the general characteristics of the linguistic deficits, the
importance of language in diagnosis and prognosis, mother-child linguistic interaction, and
intervention programs is reviewed. Recent psycholinguistic studies in normal development
point up the present inadequacies or lack of structural linguistic studies in childhood
psychosis. Some assumptions about innate linguistic capacities prerequisite to normal
development are discussed and a hypothesis relating to a dysfunction in these capacities in
childhood psychosis as well as directions for further research are proposed
348. Banaschewski T, Brandeis D. Annotation: what electrical brain activity tells us about brain
function that other techniques cannot tell us - a child psychiatric perspective. J Child
Psychol Psychiatry 2007;48(5):415-435.
Ref ID: 5325
Abstract: BACKGROUND: Monitoring brain processes in real time requires genuine
subsecond resolution to follow the typical timing and frequency of neural events.
Non-invasive recordings of electric (EEG/ERP) and magnetic (MEG) fields provide this time
resolution. They directly measure neural activations associated with a wide variety of brain
states and processes, even during sleep or in infants. Mapping and source estimation can
localise these time-varying activation patterns inside the brain. METHODS: Recent
EEG/ERP research on brain functions in the domains of attention and executive
functioning, perception, memory, language, emotion and motor processing in ADHD,
autism, childhood-onset schizophrenia, Tourette syndrome, specific language disorder and
developmental dyslexia, anxiety, obsessive-compulsive disorder, and depression is
reviewed. RESULTS: Over the past two decades, electrophysiology has substantially
contributed to the understanding of brain functions during normal development, and
psychiatric conditions of children and adolescents. Its time resolution has been important to
measure covert processes, and to distinguish cause and effect. CONCLUSIONS: In the
future, EEG/ERP parameters will increasingly characterise the interplay of neural states
and information processing. They are particularly promising tools for multilevel
investigations of etiological pathways and potential predictors of clinical treatment response
349. Bao S, Chang EF, Woods J, Merzenich MM. Temporal plasticity in the primary auditory
cortex induced by operant perceptual learning. Nat Neurosci 2004;7(9):974-981.
Ref ID: 4897
Abstract: Processing of rapidly successive acoustic stimuli can be markedly improved by
sensory training. To investigate the cortical mechanisms underlying such temporal
plasticity, we trained rats in a 'sound maze' in which navigation using only auditory cues led
to a target location paired with food reward. In this task, the repetition rate of noise pulses
increased as the distance between the rat and target location decreased. After training in
the sound maze, neurons in the primary auditory cortex (A1) showed greater responses to
high-rate noise pulses and stronger phase-locking of responses to the stimuli; they also
showed shorter post-stimulation suppression and stronger rebound activation. These
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improved temporal dynamics transferred to trains of pure-tone pips. Control animals that
received identical sound stimulation but were given free access to food showed the same
results as naive rats. We conclude that this auditory perceptual learning results in
improvements in temporal processing, which may be mediated by enhanced cortical
response dynamics
350. Bao S, Chang EF, Davis JD, Gobeske KT, Merzenich MM. Progressive degradation and
subsequent refinement of acoustic representations in the adult auditory cortex. J Neurosci
2003;23(34):10765-10775.
Ref ID: 4898
Abstract: Correlated neuronal activity is believed to play an important role in refining and
maintaining cortical circuitry during early development. Here we provide evidence that
globally and locally correlated activity mediate different forms of adult plasticity. Pulses of
broad-spectrum noise were used to activate time-locked responses across large areas of
the rat auditory cortex, globally synchronizing cortical activity. Brief tone pips were used to
activate relatively small groups of neurons, generating locally correlated activity. Pairing
pulsed noises with nucleus basalis (NB) stimulation in awake rats for 4 weeks broadened
spectral tuning, disrupted tonotopic maps, and reduced spontaneous discharge correlation
in the primary auditory cortex (AI), as examined under anesthesia. Those effects caused AI
neurons to appear qualitatively similar to neurons in nonprimary auditory fields of naive
animals. Subsequent pairing of tone pips with NB stimulation for a period of 4 weeks
completely reversed these effects induced by previous noise-NB pairing. These findings
further demonstrate that the adult auditory cortex retains a substantial capacity for
receptive field plasticity and tonotopic map reorganization and that locally correlated activity
plays an important role in plasticity in the adult, as in the developing cortex
351. Bao S, Chan VT, Merzenich MM. Cortical remodelling induced by activity of ventral
tegmental dopamine neurons. Nature 2001;412(6842):79-83.
Ref ID: 4901
Abstract: Representations of sensory stimuli in the cerebral cortex can undergo progressive
remodelling according to the behavioural importance of the stimuli. The cortex receives
widespread projections from dopamine neurons in the ventral tegmental area (VTA), which
are activated by new stimuli or unpredicted rewards, and are believed to provide a
reinforcement signal for such learning-related cortical reorganization. In the primary
auditory cortex (AI) dopamine release has been observed during auditory learning that
remodels the sound-frequency representations. Furthermore, dopamine modulates
long-term potentiation, a putative cellular mechanism underlying plasticity. Here we show
that stimulating the VTA together with an auditory stimulus of a particular tone increases
the cortical area and selectivity of the neural responses to that sound stimulus in AI.
Conversely, the AI representations of nearby sound frequencies are selectively decreased.
Strong, sharply tuned responses to the paired tones also emerge in a second cortical area,
whereas the same stimuli evoke only poor or non-selective responses in this second
cortical field in naive animals. In addition, we found that strong long-range coherence of
neuronal discharge emerges between AI and this secondary auditory cortical area
352. Bara BG, Bosco FM, Bucciarelli M. Developmental pragmatics in normal and abnormal
children. Brain Lang 1999;68(3):507-528.
Ref ID: 3310
Abstract: We propose a critical review of current theories of developmental pragmatics. The
underlying assumption is that such a theory ought to account for both normal and abnormal
development. From a clinical point of view, we are concerned with the effects of brain
damage on the emergence of pragmatic competence. In particular, the paper deals with
direct speech acts, indirect speech acts, irony, and deceit in children with head injury,
closed head injury, hydrocephalus, focal brain damage, and autism. Since no single theory
covers systematically the emergence of pragmatic capacity in normal children, it is not
surprising that we have not found a systematic account of deficits in the communicative
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performance of brain injured children. In our view, the challenge for a pragmatic theory is
the determination of the normal developmental pattern within which different pragmatic
phenomena may find a precise role. Such a framework of normal behavior would then
permit the systematic study of abnormal pragmatic development. Copyright 1999 Academic
Press
353. Barabas G, Matthews WS. Coincident infantile autism and Tourette syndrome: a case
report. JDBP 1983;4(4):280-281.
Ref ID: 2325
Abstract: A 15-year-old boy who had been diagnosed as having infantile autism (IA) at two
years of age was found to have Tourette Syndrome (TS) in adolescence. This case report
represents the second coincident finding of IA and TS in an adolescent autistic boy. The
implications of a co-occurrence of IA and TS are discussed in the light of our current
understanding of abnormalities in neurotransmitter metabolism common to both conditions
354. Baranek GT, Boyd BA, Poe MD, David FJ, Watson LR. Hyperresponsive sensory patterns
in young children with autism, developmental delay, and typical development. Am J Ment
Retard 2007;112(4):233-245.
Ref ID: 5088
Abstract: The nature of hyperresponsiveness to sensory stimuli in children with autism,
using a new observational measure, the SPA, was examined. Three groups of young
participants were assessed (autism, developmental delay, typical). Across all groups, MA
was a predictor of hyperresponsiveness, such that aversion to multisensory toys decreased
as MA increased. The two clinical groups displayed higher levels of sensory aversion than
the typical group. The groups did not differ in the proportion of children habituating to an
auditory stimulus; however, nonresponders were more prevalent in the autism group.
These findings elucidate developmental influences on sensory features and the specificity
of hyperresponsiveness to clinical groups. Implications for understanding pathogenesis,
differentiating constructs of hypersensitivity, and planning treatment are discussed
355. Baranek GT. Efficacy of sensory and motor interventions for children with autism. J Autism
Dev Disord 2002;32(5):397-422.
Ref ID: 4759
Abstract: Idiosyncratic responses to sensory stimuli and unusual motor patterns have been
reported clinically in young children with autism. The etiology of these behavioral features is
the subject of much speculation. Myriad sensory- and motor-based interventions have
evolved for use with children with autism to address such issues; however, much
controversy exists about the efficacy of such therapies. This review paper summarizes the
sensory and motor difficulties often manifested in autism, and evaluates the scientific basis
of various sensory and motor interventions used with this population. Implications for
education and further research are described
356. Baranek GT. Autism during infancy: a retrospective video analysis of sensory-motor and
social behaviors at 9-12 months of age. J Autism Dev Disord 1999;29(3):213-224.
Ref ID: 3514
Abstract: This retrospective video study explored the usefulness of sensory-motor
measures in addition to social behaviors as early predictors of autism during infancy. Three
groups included 11 children with autism, 10 with developmental disabilities, and 11 typically
developing children. Home videos were edited to obtain a 10-minute cross-section of
situations at 9-12 months for each subjects. Using interval scoring, raters coded several
behavioral categories (i.e., Looking, Affect, Response to Name, Anticipatory Postures,
Motor/Object Stereotypies, Social Touch, Sensory Modulation). Nine items, in combination,
were found to discriminate the three groups with a correct classification rate of 93.75%.
These findings indicate that subtle symptoms of autism are present at 9-12 months, and
suggest that early assessment procedures need to consider sensory
processing/sensory-motor functions in addition to social responses during infancy.
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Furthermore, prior to a time that they reported autistic symptoms, caregivers used
compensatory strategies to increase the saliency of stimuli in order to engage their children
more successfully; these strategies may provide a window for earlier diagnosis
357. Baranek GT, Foster LG, Berkson G. Tactile defensiveness and stereotyped behaviors. Am
J Occup Ther 1997;51(2):91-95.
Ref ID: 4760
Abstract: OBJECTIVES: This study explores the constructs of stereotyped behaviors (e.g.,
repetitive motor patterns, object manipulations, behavioral rigidities) and tactile
defensiveness as relevant to occupational therapy theory and practice and attempts to test
their purported relationships in children with developmental disabilities. METHOD:
Twenty-eight children with developmental disabilities and autism were assessed on eight
factors of stereotyped behavior via a questionnaire and by four measures of tactile
defensiveness. The subjects' scores from the questionnaire were correlated with their
scores on the tactile defensiveness measures to see what, if any, relationship among these
behaviors exists. RESULTS: Significant relationships emerged from the data, indicating
that subjects with higher levels of tactile defensiveness were also more likely to evidence
rigid or inflexible behaviors, repetitive verbalizations, visual stereotypes, and abnormal
focused affections that are often associated with autism. No significant association was
found between motor and object stereotypes and tactile defensiveness. These relationships
could not be explained solely by maturational factors. CONCLUSION: The results suggest
that clinicians should include observations of stereotyped behaviors, particularly behavioral
rigidities, in conjunction with assessments of sensory defensiveness because these are
related phenomena that may pose unique challenges for children with developmental
disabilities and autism. Further study is needed to determine the causal mechanisms
responsible for these relationships
358. Barber AD, Srinivasan P, Joel SE, Caffo BS, Pekar JJ, Mostofsky SH. Motor "dexterity"?:
Evidence that left hemisphere lateralization of motor circuit connectivity is associated with
better motor performance in children. Cereb Cortex 2012;22(1):51-59.
Ref ID: 7351
Abstract: Motor control relies on well-established motor circuits, which are critical for typical
child development. Although many imaging studies have examined task activation during
motor performance, none have examined the relationship between functional intrinsic
connectivity and motor ability. The current study investigated the relationship between
resting state functional connectivity within the motor network and motor performance
assessment outside of the scanner in 40 typically developing right-handed children. Better
motor performance correlated with greater left-lateralized (mean left hemisphere-mean right
hemisphere) motor circuit connectivity. Speed, rhythmicity, and control of movements were
associated with connectivity within different individual region pairs: faster speed was
associated with more left-lateralized putamen-thalamus connectivity, less overflow with
more left-lateralized supplementary motor-primary motor connectivity, and less dysrhythmia
with more left-lateralized supplementary motor-anterior cerebellar connectivity. These
findings suggest that for right-handed children, superior motor development depends on the
establishment of left-hemisphere dominance in intrinsic motor network connectivity
359. Barker DF, Pruchno CJ, Jiang X et al. A mutation causing Alport syndrome with tardive
hearing loss is common in the western United States. Am J Hum Genet
1996;58(6):1157-1165.
Ref ID: 1866
360. Barkley RA. Issues in the diagnosis of attention-deficit/hyperactivity disorder in children.
Brain Dev 2003;25(2):77-83.
Ref ID: 3707
Abstract: This paper provides a brief overview of the nature of attention-deficit/hyperactivity
disorder (ADHD) in children and the current criteria used in its clinical diagnosis. While the
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disorder continues to be viewed as one of inattention and/or hyperactive-impulsive
behavior, theories of ADHD are beginning to focus more on poor inhibition and deficient
executive functioning (self-regulation) as being central to the disorder. Problems have been
identified by research pertaining to the clinical diagnostic criteria outlined in the DSM-IV
that, at present, remain unresolved. Clinicians should be aware of these problems and the
adjustments that need to be made to them when dealing with special populations that were
not represented in the field trials used to develop these criteria
361. Barkley RA. Commentary: issues in training parents to manage children with behavior
problems . J Am Acad Child Adolesc Psychiatry 2000;39(8):1004-1007.
Ref ID: 3190
362. Barkley RA, Grodzinsky GM. Are tests of frontal lobe functions useful in the diagnosis of
attention deficit disorders? Clin Neuropsychol 1994;8:121-139.
Ref ID: 1427
363. Barkley RA. The ecologic validity of laboratory and analogue assessment methods of
ADHD symptoms. J Abn Child Psychol 1991;19:149-178.
Ref ID: 1426
364. Barkley RA. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and
Treatment. New York: Guilford; 1990.
Ref ID: 1439
365. Barkovich AJ. Pediatric neuroimaging. Philadelphia PA: Lippincott Williams & Wilkins;
2005.
Ref ID: 5630
366. Barkovich AJ. Pediatric Neuroimaging. 3 ed. Philadelphia: Lippincott Williams & Wilkins;
2000.
Ref ID: 3138
367. Barkovich AJ, Ferriero DM, Barr RM et al. Microlissencephaly: a heterogeneous
malformation of cortical development [see comments]. Neuropediatrics
1998;29(3):113-119.
Ref ID: 3069
Abstract: We report the neonatal courses, early postnatal development, and neuroimaging
findings of 17 patients with marked microcephaly and simplified cerebral gyral patterns, a
condition that we call microlissencephaly. Retrospective analyses of the clinicoradiologic
features of these patients allowed segregation of the patients into 5 distinct groups with
varying outcomes. The apparent discreteness of these groups suggests multiple etiologies
of this malformation, although there appears to be a strong genetic component with
probable autosomal recessive inheritance. Utilizing the neonatal course and
neuroradiologic features of these infants allows classification of specific subsets, which
may be useful to predict outcome
368. Barlow WE, Davis RL, Glasser JW et al. The risk of seizures after receipt of whole-cell
pertussis or measles, mumps, and rubella vaccine. N Engl J Med 2001;345(9):656-661.
Ref ID: 3685
Abstract: BACKGROUND: The administration of the diphtheria and tetanus toxoids and
whole-cell pertussis (DTP) vaccine and measles, mumps, and rubella (MMR) vaccine has
been associated with adverse neurologic events, including seizures. We studied the
relation between these vaccinations and the risk of a first seizure, subsequent seizures,
and neurodevelopmental disability in children. METHODS: This cohort study was
conducted at four large health maintenance organizations and included reviews of the
medical records of children with seizures. We calculated the relative risks of febrile and
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nonfebrile seizures among 679,942 children after 340,386 vaccinations with DTP vaccine,
137,457 vaccinations with MMR vaccine, or no recent vaccination. Children who had febrile
seizures after vaccination were followed to identify the risk of subsequent seizures and
other neurologic disabilities. RESULTS: Receipt of DTP vaccine was associated with an
increased risk of febrile seizures only on the day of vaccination (adjusted relative risk, 5.70;
95 percent confidence interval, 1.98 to 16.42). Receipt of MMR vaccine was associated
with an increased risk of febrile seizures 8 to 14 days after vaccination (relative risk, 2.83;
95 percent confidence interval, 1.44 to 5.55). Neither vaccination was associated with an
increased risk of nonfebrile seizures. Analyses of automated data alone gave results similar
to the analyses of the data from medical-record reviews. The number of febrile seizures
attributable to the administration of DTP and MMR vaccines was estimated to be 6 to 9 and
25 to 34 per 100,000 children, respectively. As compared with other children with febrile
seizures that were not associated with vaccination, the children who had febrile seizures
after vaccination were not found to be at higher risk for subsequent seizures or
neurodevelopmental disabilities. CONCLUSIONS: There are significantly elevated risks of
febrile seizures on the day of receipt of DTP vaccine and 8 to 14 days after the receipt of
MMR vaccine, but these risks do not appear to be associated with any long-term, adverse
consequences
369. Barnard L, Young AH, Pearson J, Geddes J, O'Brien G. A systematic review of the use of
atypical antipsychotics in autism. J Psychopharmacol 2002;16(1):93-101.
Ref ID: 3992
Abstract: Conventional antipsychotic medication is commonly prescribed to patients with
autistic spectrum disorder. However, a high incidence of severe adverse reactions
highlights the need to find more favourable treatments. Atypical antipsychotics may
combine efficacy in ameliorating some autistic symptoms with a lower incidence of some
adverse reactions. This article reviews the use of atypical antipsychotics in autistic disorder,
with particular focus on behaviour, cognition and physical well-being. Thirteen studies using
risperidone, three using olanzapine, one using clozapine, one using amisulpride and one
using quetiapine were identified. Few firm conclusions can be drawn due to the limitations
of the studies; however, there is an indication that risperidone may be effective in reducing
hyperactivity, aggression and repetitive behaviours, often without inducing severe adverse
reactions. Olanzapine and clozapine may also be effective; however, there is little evidence
for using amisulpride or quetiapine in this population. Randomized trials are required to
clarify the effectiveness of these agents
370. Barnby G, Abbott A, Sykes N et al. Candidate-gene screening and association analysis at
the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A
and ABAT. Am J Hum Genet 2005;76(6):950-966.
Ref ID: 6532
Abstract: Autism is a highly heritable neurodevelopmental disorder whose underlying
genetic causes have yet to be identified. To date, there have been eight genome screens
for autism, two of which identified a putative susceptibility locus on chromosome 16p. In the
present study, 10 positional candidate genes that map to 16p11-13 were examined for
coding variants: A2BP1, ABAT, BFAR, CREBBP, EMP2, GRIN2A, MRTF-B, SSTR5, TBX6,
and UBN1. Screening of all coding and regulatory regions by denaturing high-performance
liquid chromatography identified seven nonsynonymous changes. Five of these mutations
were found to cosegregate with autism, but the mutations are not predicted to have
deleterious effects on protein structure and are unlikely to represent significant etiological
variants. Selected variants from candidate genes were genotyped in the entire International
Molecular Genetics Study of Autism Consortium collection of 239 multiplex families and
were tested for association with autism by use of the pedigree disequilibrium test.
Additionally, genotype frequencies were compared between 239 unrelated affected
individuals and 192 controls. Patterns of linkage disequilibrium were investigated, and the
transmission of haplotypes across candidate genes was tested for association. Evidence of
single-marker association was found for variants in ABAT, CREBBP, and GRIN2A. Within
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these genes, 12 single-nucleotide polymorphisms (SNPs) were subsequently genotyped in
91 autism trios (one affected individual and two unaffected parents), and the association
was replicated within GRIN2A (Fisher's exact test, P<.0001). Logistic regression analysis of
SNP data across GRIN2A and ABAT showed a trend toward haplotypic differences
between cases and controls
371. Barnea-Goraly N, Kwon H, Menon V, Eliez S, Lotspeich L, Reiss AL. White matter structure
in autism: preliminary evidence from diffusion tensor imaging. Biol Psychiatry
2004;55(3):323-326.
Ref ID: 4284
Abstract: BACKGROUND: Individuals with autism have severe difficulties in social
communication and relationships. Prior studies have suggested that abnormal connections
between brain regions important for social cognition may contribute to the social deficits
seen in autism. METHODS: In this study, we used diffusion tensor imaging to investigate
white matter structure in seven male children and adolescents with autism and nine age-,
gender-, and IQ-matched control subjects. RESULTS: Reduced fractional anisotropy (FA)
values were observed in white matter adjacent to the ventromedial prefrontal cortices and
in the anterior cingulate gyri as well as in the temporoparietal junctions. Additional clusters
of reduced FA values were seen adjacent to the superior temporal sulcus bilaterally, in the
temporal lobes approaching the amygdala bilaterally, in occipitotemporal tracts, and in the
corpus callosum. CONCLUSIONS: Disruption of white matter tracts between regions
implicated in social functioning may contribute to impaired social cognition in autism
372. Barneveld PS, Pieterse J, de SL et al. Overlap of autistic and schizotypal traits in
adolescents with Autism Spectrum Disorders. Schizophr Res 2011;126(1-3):231-236.
Ref ID: 7085
Abstract: This study addresses the unraveling of the relationship between autism spectrum
and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum
Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders
as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical
phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically
developing adolescents, matched for age and gender, participated in this study. Within the
ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality
disorders. Autistic and schizotypal traits were identified by means of well validated
questionnaires (Autism Questionnaire, AQ and Schizotypal Personality
Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD
were found than in typically developing controls. Besides high levels of negative symptoms,
adolescents with ASD also displayed high levels of positive and disorganized symptoms.
There appeared to be a relationship between the mean level of autistic symptoms and
schizotypal traits, as well as specific associations between autistic symptoms and negative,
disorganized and positive schizotypal symptoms within individuals. Schizotypal
symptomatology in all sub dimensions that are reflected by the SPQ scores, was most
prominently associated with attention switching problems of the autism symptoms from the
AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia
spectrum traits in adolescence. Although other studies have provided empirical support for
this overlap in diagnostic criteria between both spectrum disorders, the present findings
add to the literature that behavioral overlap is not limited to negative schizotypal symptoms,
but extends to disorganized and positive symptoms as well
373. Baron-Cohen S, Auyeung B, Ashwin E, Knickmeyer R. Fetal testosterone and autistic traits:
a response to three fascinating commentaries. Br J Psychol 2009;100(Pt 1):39-47.
Ref ID: 6762
Abstract: This article is an author response to three previous commentaries on 'Fetal
testosterone and autistic traits' (Auyeung et al., 2009).
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374. Baron-Cohen S, Knickmeyer RC, Belmonte MK. Sex differences in the brain: implications
for explaining autism. Science 2005;310(5749):819-823.
Ref ID: 4613
Abstract: Empathizing is the capacity to predict and to respond to the behavior of agents
(usually people) by inferring their mental states and responding to these with an
appropriate emotion. Systemizing is the capacity to predict and to respond to the behavior
of nonagentive deterministic systems by analyzing input-operation-output relations and
inferring the rules that govern such systems. At a population level, females are stronger
empathizers and males are stronger systemizers. The "extreme male brain" theory posits
that autism represents an extreme of the male pattern (impaired empathizing and
enhanced systemizing). Here we suggest that specific aspects of autistic neuroanatomy
may also be extremes of typical male neuroanatomy
375. Baron-Cohen S, Wheelwright S. The empathy quotient: an investigation of adults with
Asperger syndrome or high functioning autism, and normal sex differences. J Autism Dev
Disord 2004;34(2):163-175.
Ref ID: 4553
Abstract: Empathy is an essential part of normal social functioning, yet there are precious
few instruments for measuring individual differences in this domain. In this article we review
psychological theories of empathy and its measurement. Previous instruments that purport
to measure this have not always focused purely on empathy. We report a new self-report
questionnaire, the Empathy Quotient (EQ), for use with adults of normal intelligence. It
contains 40 empathy items and 20 filler/control items. On each empathy item a person can
score 2, 1, or 0, so the EQ has a maximum score of 80 and a minimum of zero. In Study 1
we employed the EQ with n = 90 adults (65 males, 25 females) with Asperger Syndrome
(AS) or high-functioning autism (HFA), who are reported clinically to have difficulties in
empathy. The adults with AS/HFA scored significantly lower on the EQ than n = 90 (65
males, 25 females) age-matched controls. Of the adults with AS/HFA, 81% scored equal to
or fewer than 30 points out of 80, compared with only 12% of controls. In Study 2 we
carried out a study of n = 197 adults from a general population, to test for previously
reported sex differences (female superiority) in empathy. This confirmed that women
scored significantly higher than men. The EQ reveals both a sex difference in empathy in
the general population and an empathy deficit in AS/HFA
376. Baron-Cohen S. The extreme male brain theory of autism. In: Tager-Flusberg H, editor.
Neurodevelopmental disorders. Boston: MIT Press/Bradford Books; 2001.
Ref ID: 3378
377. Baron-Cohen S, Wheelwright S, Skinner R, Martin J, Clubley E. The Autism-Spectrum
Quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and
females, scientists and mathematicians. J Autism Dev Disord 2001;31(1):5-17.
Ref ID: 3620
Abstract: Currently there are no brief, self-administered instruments for measuring the
degree to which an adult with normal intelligence has the traits associated with the autistic
spectrum. In this paper, we report on a new instrument to assess this: the Autism-Spectrum
Quotient (AQ). Individuals score in the range 0-50. Four groups of subjects were assessed:
Group 1: 58 adults with Asperger syndrome (AS) or high-functioning autism (HFA); Group
2: 174 randomly selected controls. Group 3: 840 students in Cambridge University; and
Group 4: 16 winners of the UK Mathematics Olympiad. The adults with AS/HFA had a
mean AQ score of 35.8 (SD = 6.5), significantly higher than Group 2 controls (M = 16.4, SD
= 6.3). 80% of the adults with AS/HFA scored 32+, versus 2% of controls. Among the
controls, men scored slightly but significantly higher than women. No women scored
extremely highly (AQ score 34+) whereas 4% of men did so. Twice as many men (40%) as
women (21%) scored at intermediate levels (AQ score 20+). Among the AS/HFA group,
male and female scores did not differ significantly. The students in Cambridge University
did not differ from the randomly selected control group, but scientists (including
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mathematicians) scored significantly higher than both humanities and social sciences
students, confirming an earlier study that autistic conditions are associated with scientific
skills. Within the sciences, mathematicians scored highest. This was replicated in Group 4,
the Mathematics Olympiad winners scoring significantly higher than the male Cambridge
humanities students. 6% of the student sample scored 32+ on the AQ. On interview, 11 out
of 11 of these met three or more DSM-IV criteria for AS/HFA, and all were studying
sciences/mathematics, and 7 of the 11 met threshold on these criteria. Test-retest and
interrater reliability of the AQ was good. The AQ is thus a valuable instrument for rapidly
quantifying where any given individual is situated on the continuum from autism to
normality. Its potential for screening for autism spectrum conditions in adults of normal
intelligence remains to be fully explored
378. Baron-Cohen S, Ring HA, Bullmore ET, Wheelwright S, Ashwin C, Williams SC. The
amygdala theory of autism. Neurosci Biobehav Rev 2000;24(3):355-364.
Ref ID: 3123
Abstract: Brothers (Brothers L. Concepts in Neuroscience 1990;1:27-51) proposed a
network of neural regions that comprise the "social brain", which includes the amygdala.
Since the childhood psychiatric condition of autism involves deficits in "social intelligence",
it is plausible that autism may be caused by an amygdala abnormality. In this paper we
review the evidence for a social function of the amygdala. This includes reference to the
Kluver-Bucy syndrome (which Hetzler and Griffin suggested may serve as an animal model
of autism). We then review evidence for an amygdala deficit in people with autism, who are
well known to have deficits in social behaviour. This includes a detailed summary of our
recent functional magnetic resonance imaging (fMRI) study involving judging from the
expressions of another person's eyes what that other person might be thinking or feeling. In
this study, patients with autism or AS did not activate the amygdala when making
mentalistic inferences from the eyes, whilst people without autism did show amygdala
activity. The amygdala is therefore proposed to be one of several neural regions that are
abnormal in autism. We conclude that the amygdala theory of autism contains promise and
suggest some new lines of research
379. Baron-Cohen S, Wheelwright S, Cox A et al. Early identification of autism by the CHecklist
for Autism in Toddlers (CHAT). J R Soc Med 2000;93(10):521-525.
Ref ID: 3621
380. Baron-Cohen S. Is Asperger syndrome/high-functioning autism necessarily a disability?
Dev Psychopathol 2000;12(3):489-500.
Ref ID: 3622
Abstract: This article considers whether Asperger syndrome (AS) or high-functioning autism
(HFA) necessarily leads to disability or whether AS/HFA simply leads to "difference." It
concludes that the term "difference" in relation to AS/ HFA is a more neutral, value-free,
and fairer description than terms such as "impairment," "deficiency," or "disability"; that the
term "disability" only applies to the lower functioning cases of autism; but that the term
"disability" may need to be retained for ASIHFA as long as the legal framework provides
financial and other support only for individuals with a disability. Two models are
summarized which attempt to define in what way individuals with AS/HFA are "different":
the central coherence model, and the folk psychology-folk physics model. The challenge for
research is to test the value of such models and to precisely characterize the differences in
cognitive style
381. Baron-Cohen S, Ring HA, Wheelwright S et al. Social intelligence in the normal and autistic
brain: an fMRI study. European Journal of Neuroscience 1999;11(6):1891-1898.
Ref ID: 2927
Abstract: There is increasing support for the existence of 'social intelligence' [Humphrey
(1984) Consciousness Regained], independent of general intelligence. Brothers et al. 1990)
J. Cog. Neurosci., 4, 107-118] proposed a network of neural regions that comprise the
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'social brain': the orbito-frontal cortex (OFC), superior temporal gyrus (STG) and amygdala.
We tested Brothers' theory by examining both normal subjects as well as patients with
high-functioning autism or Asperger syndrome (AS), who are well known to have deficits in
social intelligence, and perhaps deficits in amygdala function [Bauman & Kemper (1988) J.
Neuropath. Exp. Neurol., 47, 369]. We used a test of judging from the expressions of
another person's eyes what that other person might be thinking or feeling. Using functional
magnetic resonance imaging (fMRI) we confirmed Brothers' prediction that the STG and
amygdala show increased activation when using social intelligence. Some areas of the
prefrontal cortex also showed activation. In contrast, patients with autism or AS activated
the fronto-temporal regions but not the amygdala when making mentalistic inferences from
the eyes. These results provide support for the social brain theory of normal function, and
the amygdala theory of autism
3Unique Identifier98429157*AuthorsxRuter M. InstitutionxMRC Child Pychaty Unit and
Istitute of Psyciatry, London, UK. TitlexRoutes from research to clinical practice in child
psychiatry: retrospectandprospect.[Review][169refs]xSourcexJournal of Child Psychology &
Psychiatry & Allied Disciplines. 39(6):805-16, 1998 Sep. Abbreviated
SourcexJChildPsycholPsychiatry.39(6):805-16,1998Sep.xNLM Journal Codev
382. Baron-Cohen S, Mortimore C, Moriarty J, Izaguirre J, Robertson M. The prevalence of
Gilles de la Tourette's syndrome in children and adolescents with autism. J Child Psychol
Psychiatry 1999;40(2):213-218.
Ref ID: 3311
Abstract: Thirty-seven pupils attending a special school for children and adolescents with
autism were observed for the presence of motor and vocal tics. Subsequent family
interviews confirmed the diagnosis of comorbid Gilles de la Tourette's Syndrome (GTS) in
three children with autism, giving a minimum prevalence rate of 8.1 %. Family history data
also suggested this was heritable. The presence of GTS was not associated with superior
intellectual, language, or social development. Results suggest that the rate of GTS in
autism may exceed that expected by chance. The limited sample size constrains this
conclusion. A large- scale epidemiological study testing this association study would
appear merited
383. Baron-Cohen S. The study of autism reveals evolved mechanisms for mindreading. Natural
History 1997.
Ref ID: 1738
384. Baron-Cohen S, Swettenham J. Theory of mind in autism: Its relationship to executive
function and general coherence. In: Cohen DJ, Volkmar FR, editors. Handbook of Autism
and Pervasive Developmental Disorders. 2 ed. New York: John Wiley & Sons;
1997:880-893.
Ref ID: 2277
385. Baron-Cohen S, Jolliffe T, Mortimore C, Robertson M. Another advanced test of theory of
mind: evidence from very high functioning adults with autism or Asperger syndrome. J Child
Psychol Psychiatry 1997;38(7):813-822.
Ref ID: 2456
Abstract: Previous studies have found a subgroup of people with autism or Asperger
Syndrome who pass second-order tests of theory of mind. However, such tests have a
ceiling in developmental terms corresponding to a mental age of about 6 years. It is
therefore impossible to say if such individuals are intact or impaired in their theory of mind
skills. We report the performance of very high functioning adults with autism or Asperger
Syndrome on an adult test of theory of mind ability. The task involved inferring the mental
state of a person just from the information in photographs of a person's eyes. Relative to
age-matched normal controls and a clinical control group (adults with Tourette Syndrome),
the group with autism and Asperger Syndrome were significantly impaired on this task. The
autism and Asperger Syndrome sample was also impaired on Happe's strange stories
95
tasks. In contrast, they were unimpaired on two control tasks: recognising gender from the
eye region of the face, and recognising basic emotions from the whole face. This provides
evidence for subtle mindreading deficits in very high functioning individuals on the autistic
continuum
386. Baron-Cohen S, Hammer J. Is autism an extreme form of of the male brain? Advances in
Infancy Research 1997;11:193-217.
Ref ID: 3377
387. Baron-Cohen S, Cox A, Baird G et al. Psychological markers in the detection of autism in
infancy in a large population. Br J Psychiatry 1996;168(2):158-163.
Ref ID: 2357
388. Baron-Cohen S, Tager-Flusberg H, Cohen DJ, (Eds.). Understanding other minds:
perspectives from autism. Oxford GB: Oxford University Press; 1993.
Ref ID: 185
389. Baron-Cohen S, Allen J, Gillberg C. Can autism be detected at 18 months? The needle, the
haystack, and the CHAT. Br J Psychiatry 1992;161:839-843.
Ref ID: 1412
390. Baron-Cohen S. Do people with autism understand what causes emotions? Child Dev
1991;62:385-395.
Ref ID: 903
391. Baron-Cohen S. The development of a theory of mind: Deviance or delay? Psychiat Clin N
Am 1991;14(1):33-51.
Ref ID: 2128
392. Baron-Cohen S. Do autistic children have obsessions and compulsions? Brit J Clin Psychol
1989;28:193-200.
Ref ID: 33
393. Baron-Cohen S, Leslie AM, Frith U. Does the autistic child have a "theory of mind"?
Cognition 1985;21:37-46.
Ref ID: 119
394. Baron IS, Anderson PJ. Neuropsychological assessment of preschoolers. Neuropsychol
Rev 2012;22(4):311-312.
Ref ID: 7432
395. Baron IS, Leonberger KA. Assessment of intelligence in the preschool period.
Neuropsychol Rev 2012;22(4):334-344.
Ref ID: 7433
Abstract: Intelligence testing has a long and revered history in psychological measurement
in childhood. Yet, the years between infancy and early childhood have been understudied
with respect to emergent intellectual and cognitive functioning. Factor analytic models of
intelligence that have demonstrated applicability when testing older children and adults
often appear inadequate in the preschool period. As more is learned about brain
development in typically developing children during these crucial years the distinctive
relationships between neural system development and intellectual functioning are being
revealed more completely. The aim of this paper was to provide a brief historical
background as a foundation for discussion of intelligence testing, review what is known
about the dynamic course of brain development during the preschool years, acknowledge
limitations specific to intelligence testing in young children, and provide support for
96
maintaining a comprehensive neuropsychological perspective that considers the wider
range of variables that influence intellectual functioning in the preschool period
396. Baron IS. Neuropsychological evaluation of the child. New York, NY: Oxford University
Press; 2004.
Ref ID: 4596
397. Barr CL, Sandor P. Current status of genetic studies of Gilles de la Tourette syndrome.
Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 1998;43(4):351-357.
Ref ID: 2390
Abstract: Gilles de la Tourette syndrome (TS) is a familial, neuropsychiatric disorder
characterized by chronic, intermittent motor and vocal tics. Despite strong evidence for a
genetic basis of this disorder from family, twin, and adoption studies, no convincing
evidence for genetic linkage has been reported. Numerous groups world-wide have
searched for genetic susceptibility factors for TS, testing specific candidate genes in
neurotransmitter systems as well as DNA markers with known locations. Several factors
may complicate the search for genes for this disorder, including diagnostic uncertainties,
definition of the TS phenotypic spectrum as it relates to genetic susceptibility, assortative
mating, genetic heterogeneity, and unclear mode of inheritance. In this article, we review
the evidence for the genetic basis of TS and the current status of genetic studies.
[References: 86]
398. Barr CL, Wigg KG, Zovko E, Sandor P, Tsui LC. Linkage study of the dopamine D5
receptor gene and Gilles de la Tourette syndrome. Am J Med Genet 1997;74(1):58-61.
Ref ID: 2387
Abstract: A defect in the dopamine system has been hypothesized as the etiological defect
in Gilles de la Tourette syndrome (TS). In this report, we test the hypothesis that the
dopamine D5 receptor locus (DRD5) is linked to the genetic susceptibility to TS in five
families studied in Canada. We tested for linkage to the dopamine D5 receptor gene using
a microsatellite polymorphism located in the same cosmid clone. Using an autosomal
dominant model with reduced penetrance, we were able to exclude linkage in four of the
five families for the TS and chronic multiple tics (CMT) phenotype. Also, no evidence for
linkage was found using nonparametric methods in all five families
399. Barr CL, Wigg KG, Zovko E, Sandor P, Tsui LC. No evidence for a major gene effect of the
dopamine D4 receptor gene in the susceptibility to Gilles de la Tourette syndrome in five
Canadian families. Am J Med Genet 1996;67(3):301-305.
Ref ID: 2388
Abstract: Gilles de la Tourette Syndrome (TS) is neuropsychiatric disorder characterized by
both motor and vocal tics affecting approximately 1/10,000 females and 1/2000 males.
Because of the success of neuroleptics and other agents interacting with the dopaminergic
system in the suppression of tics, a defect in the dopamine system has been hypothesized
in the etiology of TS. In this paper we test the hypothesis that the dopamine D4 receptor
(DRD4) is linked to the genetic susceptibility to TS in five families. We tested three
polymorphisms in the DRD4 gene and a polymorphism in the closely linked locus, tyrosine
hydroxylase (TH). We found no evidence for linkage of DRD4 or TH to TS using an
autosomal dominant model with reduced penetrance or using non-parametric methods. The
presence of a mutation that results in a truncated non-functional D4 receptor protein was
also tested for, but was not observed in these families
400. Barrett S, Prior M, Manjiviona J. Children on the borderlands of autism: differential
characteristics in social, imaginative, communicative and repetitive behaviour domains.
Autism 2004;8(1):61-87.
Ref ID: 4300
Abstract: A sample of 37 children aged 4-7 years who all showed some autistic features
was investigated. Children with a primary diagnosis of autism were compared with those
97
diagnosed with a language disorder, on behaviours within four domains; social behaviour,
imaginative activities, repetitive behaviour and communication. The aim was to identify
potentially differentiating features of the two groups using observational ratings and
questionnaire measures provided by parents and teachers. Information on participants'
intelligence and language skills was also collected. The children with autism showed
greater deficits in joint attention, functional play and pragmatic language, and engaged in
more repetitive behaviours, than the language disordered children. However, the groups
did not differ significantly on formally assessed language skills. A cluster analysis produced
three groups of children varying in level of functioning and parent-rated behaviours. The
results are informative for clinicians dealing with the challenge of differential diagnosis
401. Barron JL, Sandman CA. Self-injurious behavior and stereotypy in an institutionalized
mentally retarded population. Appl Res Ment Retard 1984;5(4):499-511.
Ref ID: 2402
Abstract: Demographic variables and behavioral characteristics of institutionalized mentally
retarded clients exhibiting both self-injurious behavior (SIB) and stereotypy, stereotypy
alone, SIB alone, or neither of these behaviors were analyzed. Overall, there were no
significant differences for the demographic variables measured. Multivariate analyses
revealed that severity and frequency of behavior, sensory handicap, and sex of the subject
were the best predictors of group membership. Moreover, this research suggests that SIB
and stereotypy can be classified as stereotyped SIB and withdrawal stereotypy,
respectively. Thus, the treatment modalities presently being applied to these behaviors
could be inappropriate. Additional evidence is discussed that supports the belief that an
organic physiological substrate or mechanism could be related to these aberrant behavior
patterns, which would necessitate a new diagnostic classification and alternative forms of
treatment
402. Barry JG, Yasin I, Bishop DV. Heritable risk factors associated with language impairments.
Genes Brain and Behavior 2007;6(1):66-76.
Ref ID: 5041
Abstract: There is a strong genetic contribution to children's language and literacy
impairments. The aim of this study was to determine which aspects of the phenotype are
familial by comparing 34 parents of probands with language/literacy impairments and 33
parents of typically developing probands. The parents responded to questionnaires
regarding previous history for language/reading impairment and participated in
psychometric testing. The psychometric test battery consisted of tests assessing
non-verbal IQ, short-term memory, articulation, receptive grammar, reading abilities and
spelling. Self-report measures demonstrated a higher prevalence of language and literacy
impairments in parents of affected probands (32%) compared with parents of unaffected
probands (6%). The two groups of parents differed significantly in their performance on the
non-word repetition, oromotor and digit span tasks. Non-word repetition gave the best
discrimination between the parent groups even when the data from the parents who
actually were impaired as ascertained by direct testing or self-report were removed from
the analyses. This suggests that non-word repetition serves as a marker of a family risk for
language impairment. The paper concludes with a discussion of issues associated with
ascertainment of specific language impairment (SLI)
403. Barry JG, Hardiman MJ, Line E, White KB, Yasin I, Bishop DV. Duration of auditory
sensory memory in parents of children with SLI: A mismatch negativity study. Brain Lang
2007.
Ref ID: 5051
Abstract: In a previous behavioral study, we showed that parents of children with SLI had a
subclinical deficit in phonological short-term memory. Here, we tested the hypothesis that
they also have a deficit in nonverbal auditory sensory memory. We measured auditory
sensory memory using a paradigm involving an electrophysiological component called the
mismatch negativity (MMN). The MMN is a measure of the brain's ability to detect a
98
difference between a frequent standard stimulus (1000Hz tone) and a rare deviant one
(1200Hz tone). Memory effects were assessed by varying the inter-stimulus interval (ISI)
between the standard and deviant. We predicted that parents of children with SLI would
have a smaller MMN than parents of typically developing children at a long ISI (3000ms),
but not at a short one (800ms). This was broadly confirmed. However, individual
differences in MMN amplitude did not correlate with measures of phonological short-term
memory. Attenuation of MMN amplitude at the longer ISI thus did not provide unambiguous
support for the hypothesis of a reduced auditory sensory memory in parents of affected
children. We conclude by reviewing possible explanations for the observed group effects
404. Barsegyan A, Mackenzie SM, Kurose BD, McGaugh JL, Roozendaal B. Glucocorticoids in
the prefrontal cortex enhance memory consolidation and impair working memory by a
common neural mechanism. Proc Natl Acad Sci U S A 2010;107(38):16655-16660.
Ref ID: 6769
Abstract: It is well established that acute administration of adrenocortical hormones
enhances the consolidation of memories of emotional experiences and, concurrently,
impairs working memory. These different glucocorticoid effects on these two memory
functions have generally been considered to be independently regulated processes. Here
we report that a glucocorticoid receptor agonist administered into the medial prefrontal
cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and
impairs working memory. Both memory effects are mediated by activation of a
membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC
to increase levels of cAMP-dependent protein kinase. These findings provide direct
evidence that glucocorticoid effects on both memory consolidation and working memory
share a common neural influence within the mPFC
405. Barta PE, Pearlson GD, Brill LB et al. Planum temporale asymmetry reversal in
schizophrenia: replication and relationship to gray matter abnormalities. Am J Psychiatry
1997;154(5):661-667.
Ref ID: 3547
Abstract: OBJECTIVE: The planum temporale, the posterior superior surface of the
superior temporal gyrus, is a highly lateralized brain structure involved with language. In
schizophrenic patients the authors previously found consistent reversal of the normal
left-larger-than- right asymmetry of planum temporale surface area. The original subjects
plus new patients and comparison subjects participated in this effort to replicate and extend
the prior study. METHOD: High-resolution magnetic resonance imaging of 28 schizophrenic
patients and 32 group- matched normal subjects was performed. The authors measured
planum temporale surface area, gray matter volume underlying the planum temporale, and
gray matter thickness. Asymmetry indices for areas and volumes were calculated.
RESULTS: Overall gray matter and total brain volume were not significantly smaller in the
patients than in the comparison subjects. As previously reported, there was striking
reversal of the normal asymmetry for planum temporale surface area in the male and
female schizophrenic subjects. Bilaterally, gray matter volume beneath the planum
temporale was smaller in the schizophrenic patients, and the gray matter thickness of the
right planum temporale was only 50% of the comparison value. Volume of planum
temporale gray matter did not show significant asymmetry in either group. CONCLUSIONS:
This study extends the finding of reversed planum temporale surface area asymmetry in
schizophrenic patients and clarifies its relationship to underlying gray matter volume.
Although right planum temporale surface area is larger than normal in schizophrenia, gray
matter volume is less than the comparison value; thus, gray matter thickness is
substantially less than normal
406. Bartak L, Rutter M, Cox A. A comparative study of infantile autism and specific
developmental receptive language disorders. III. Discriminant function analysis. J Aut
Childh Schizophr 1977;7:383-396.
Ref ID: 186
99
Abstract: A psychometric, observational, and interview study was undertaken with 47 boys,
aged 4 1/2 to 10 years, with nonverbal IQs of 70+ and a severe developmental disorder of
language comprehension. Separate discriminant function analyses, based on behavioral,
language, or cognitive features, showed little overlap between clinically defined autistic and
dysphasic subgroups. Moreover, the discrimination could be made as clearly on language
or cognitive characteristics as on social or behavioral critera. Language abnormalities and
behavioral features also intercorrelated within the autistic subgroup. It is concluded that
autism and dysphasia differ in important ways and that a cognitive deficit is an essential
part of the syndrome of autism
407. Bartak L, Rutter M. Differences between mentally retarded and normally intelligent autistic
children. Journal of Autism & Childhood Schizophrenia 1976;6:109-120.
Ref ID: 341
408. Bartak L, Rutter M, Cox A. A comparative study of infantile autism and specific
developmental receptive language disorder: I. The children. Br J Psychiatry
1975;126:127-145.
Ref ID: 1305
409. Bartenjev I, Butina MR, Potocnik M. Rare case of Cockayne syndrome with xeroderma
pigmentosum. Acta Dermatologica Venereologica 80[3], 213-214. 2000.
Ref Type: Abstract
Ref ID: 5724
410. Barth C, Fein D, Waterhouse L. Delayed match to sample in autistic children. Dev
Neuropsychol 1995;11:53-69.
Ref ID: 1200
411. Barthelemy C, Hameury, L., LeLord G. Infantile autism: exchange and development theory.
Paris: Expansion Scientifique Publications; 1995.
Ref ID: 3351
412. Bartholomeusz HH, Courchesne E, Karns CM. Relationship between head circumference
and brain volume in healthy normal toddlers, children, and adults. Neuropediatrics
2002;33(5):239-241.
Ref ID: 3915
Abstract: OBJECTIVE: To quantify the relationship between brain volume and head
circumference from early childhood to adulthood, and quantify how this relationship
changes with age. METHODS: Whole-brain volume and head circumference measures
were obtained from MR images of 76 healthy normal males aged 1.7 to 42 years.
RESULTS: Across early childhood, brain volume and head circumference both increase,
but from adolescence onward brain volume decreases while head circumference does not.
Because of such changing relationships between brain volume and head circumference
with age, a given head circumference was associated with a wide range of brain volumes.
However, when grouped appropriately by age, head circumference was shown to
accurately predict brain volume. Head circumference was an excellent prediction of brain
volume in 1.7 to 6 years old children (r = 0.93), but only an adequate predictor in 7 to 42
year olds. CONCLUSIONS: To use head circumference as an accurate indication of
abnormal brain volume in the clinic or research setting, the patient's age must be taken into
account. With knowledge of age-dependent head circumference-to-brain volume
relationship, head circumference (particularly in young children) can be an accurate, rapid,
and inexpensive indication of normalcy of brain size and growth in a clinical setting
413. Bartlett CW, Flax JF, Fermano Z et al. Gene x Gene Interaction in Shared Etiology of
Autism and Specific Language Impairment. Biol Psychiatry 2012.
Ref ID: 7247
100
Abstract: BACKGROUND: To examine the relationship between autism spectrum disorders
(ASD) and specific language impairment (SLI), family studies typically take a comparative
approach where families with one disease are examined for traits of the other disease. In
contrast, the present report is the first study with both disorders required to be present in
each family to provide a more direct test of the hypothesis of shared genetic etiology.
METHODS: We behaviorally assessed 51 families including at least one person with ASD
and at least one person with SLI (without ASD). Pedigree members were tested with 22
standardized measures of language and intelligence. Because these extended families
include a nonshared environmental contrast, we calculated heritability, not just familiality,
for each measure twice: 1) baseline heritability analysis, compared with; 2) heritability
estimates after statistically removing ASD subjects from pedigrees. RESULTS: Significant
increases in heritability on four supra-linguistic measures (including Pragmatic Judgment)
and a composite language score but not on any other measures were observed when
removing ASD subjects from the analysis, indicating differential genetic effects that are
unique to ASD. Nongenetic explanations such as effects of ASD severity or measurement
error or low score variability in ASD subjects were systematically ruled out, leaving the
hypothesis of nonadditive genetics effects as the potential source of the heritability change
caused by ASD. CONCLUSIONS: Although the data suggest genetic risk factors common
to both SLI and ASD, there are effects that seem unique to ASD, possibly caused by
nonadditive gene-gene interactions of shared risk loci
414. Bartlett CW, Flax JF, Logue MW et al. Examination of potential overlap in autism and
language loci on chromosomes 2, 7, and 13 in two independent samples ascertained for
specific language impairment. Hum Hered 2004;57(1):10-20.
Ref ID: 4333
Abstract: Specific language impairment is a neurodevelopmental disorder characterized by
impairments essentially restricted to the domain of language and language learning skills.
This contrasts with autism, which is a pervasive developmental disorder defined by multiple
impairments in language, social reciprocity, narrow interests and/or repetitive behaviors.
Genetic linkage studies and family data suggest that the two disorders may have genetic
components in common. Two samples, from Canada and the US, selected for specific
language impairment were genotyped at loci where such common genes are likely to
reside. Significant evidence for linkage was previously observed at chromosome 13q21 in
our Canadian sample (HLOD 3.56) and was confirmed in our US sample (HLOD 2.61).
Using the posterior probability of linkage (PPL) to combine evidence for linkage across the
two samples yielded a PPL over 92%. Two additional loci on chromosome 2 and 7 showed
weak evidence for linkage. However, a marker in the cystic fibrosis transmembrane
conductance regulator (7q31) showed evidence for association to SLI, confirming results
from another group (O'Brien et al. 2003). Our results indicate that using samples selected
for components of the autism phenotype may be a useful adjunct to autism genetics
415. Bartlett CW, Flax JF, Logue MW et al. A major susceptibility locus for specific language
impairment is located on 13q21. Am J Hum Genet 2002;71(1):45-55.
Ref ID: 3746
Abstract: Children who fail to develop language normally-in the absence of explanatory
factors such as neurological disorders, hearing impairment, or lack of adequate
opportunity-are clinically described as having specific language impairment (SLI). SLI has a
prevalence of approximately 7% in children entering school and is associated with later
difficulties in learning to read. Research indicates that genetic factors are important in the
etiology of SLI. Studies have consistently demonstrated that SLI aggregates in families.
Increased monozygotic versus dizygotic twin concordance rates indicate that heredity, not
just shared environment, is the cause of the familial clustering. We have collected five
pedigrees of Celtic ancestry that segregate SLI, and we have conducted genomewide
categorical linkage analysis, using model-based LOD score techniques. Analysis was
conducted under both dominant and recessive models by use of three phenotypic
classifications: clinical diagnosis, language impairment (spoken language quotient <85) and
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reading discrepancy (nonverbal IQ minus non-word reading >15). Chromosome 13 yielded
a maximum multipoint LOD score of 3.92 under the recessive reading discrepancy model.
Simulation to correct for multiple models and multiple phenotypes indicated that the
genomewide empirical P value is <.01. As an alternative measure, we also computed the
posterior probability of linkage (PPL), obtaining a PPL of 53% in the same region. One
other genomic region yielded suggestive results on chromosome 2 (multipoint LOD score
2.86, genomic P value <.06 under the recessive language impairment model). Our findings
underscore the utility of traditional LOD-score-based methods in finding genes for complex
diseases, specifically, SLI
416. Bartolucci G, Pierce SJ, Streiner D, Eppel PT. Phonological investigation of verbal autistic
and mentally retarded subjects. J Aut Childh Schizophr 1976;6:303-316.
Ref ID: 913
417. Barton JJ, Sekunova A, Sheldon C, Johnston S, Iaria G, Scheel M. Reading words, seeing
style: the neuropsychology of word, font and handwriting perception. Neuropsychologia
2010;48(13):3868-3877.
Ref ID: 7374
Abstract: The reading of text is predominantly a left hemisphere function. However, it is
also possible to process text for attributes other than word or letter identity, such as style of
font or handwriting. Anecdotal observations have suggested that processing the latter may
involve the right hemisphere. We devised a test that, using the identical stimuli, required
subjects first to match on the basis of word identity and second to match on the basis of
script style. We presented two versions, one using various computer fonts, and the other
using the handwriting of different individuals. We tested four subjects with unilateral lesions
who had been well characterized by neuropsychological testing and structural and/or
functional MRI. We found that two prosopagnosic subjects with right lateral fusiform
damage eliminating the fusiform face area and likely the right visual word form area were
impaired in completion times and/or accuracy when sorting for script style, but performed
better when sorting for word identity. In contrast, one alexic subject with left fusiform
damage showed normal accuracy for sorting by script style and normal or mildly elevated
completion times for sorting by style, but markedly prolonged reading times for sorting by
word identity. A prosopagnosic subject with right medial occipitotemporal damage sparing
areas in the lateral fusiform gyrus performed well on both tasks. The contrast in the
performance of patients with right versus left fusiform damage suggests an important
distinction in hemispheric processing that reflects not the type of stimulus but the nature of
processing required
418. Barton M, Volkmar F. How commonly are known medical conditions associated with
autism? J Autism Dev Disord 1998;28(4):273-278.
Ref ID: 2150
419. Basauri L, Selman JM. Intracranial arachnoidal cysts. Child's Nervous System
1992;8(2):101-104.
Ref ID: 17
Abstract: Twenty-eight cases of intracranial arachnoidal cysts diagnosed during the period
1978-1990 are analyzed. All cases were investigated with computed tomography (CT), 5
with magnetic resonance imaging (MRI) and 5 with ultrasonography (US). Seventeen were
located in the middle cranial fossa, 3 in the quadrigeminal cistern, 2 were parasagittal, 3
suprasellar and 3 were located in the posterior fossa. Twenty-three of the 28 patients were
treated surgically, craniotomy with fenestrations was used in 3 cases. Different varieties of
shunts were inserted in 8 cases and in the last 15 patients the only surgical treatment was
the insertion of cysto-peritoneal (CP) drainage (without a valve) with excellent results. MRI
and/or CT follow-up revealed disappearance of the cyst in 13 out of 22 cases and 7
experienced a marked reduction. In 2 patients the cyst showed little change. There were no
cases of infection and no deaths
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420. Basser LS. Hemiplegia of early onset and the faculty of speech with special reference to
the effects of hemispherectory. Brain 1962;85:427-460.
Ref ID: 701
421. Basu M, Krishnan A, Weber-Fox C. Brainstem correlates of temporal auditory processing in
children with specific language impairment
15. Dev Sci 2010;13(1):77-91.
Ref ID: 7300
Abstract: Deficits in identification and discrimination of sounds with short inter-stimulus
intervals or short formant transitions in children with specific language impairment (SLI)
have been taken to reflect an underlying temporal auditory processing deficit. Using the
sustained frequency following response (FFR) and the onset auditory brainstem responses
(ABR) we evaluated if children with SLI show abnormalities at the brainstem level
consistent with a temporal processing deficit. To this end, the neural encoding of tonal
sweeps, as reflected in the FFR, for different rates of frequency change, and the effects of
reducing inter-stimulus interval on the ABR components were evaluated in 10 4-11-year-old
SLI children and their age-matched controls. Results for the SLI group showed degraded
FFR phase-locked neural activity that failed to faithfully track the frequency change
presented in the tonal sweeps, particularly at the faster sweep rates. SLI children also
showed longer latencies for waves III and V of the ABR and a greater prolongation of wave
III at high stimulus rates (>30/sec), suggesting greater susceptibility to neural adaptation.
These results taken together appear to suggest a disruption in the temporal pattern of
phase-locked neural activity necessary to encode rapid frequency change and an
increased susceptibility to desynchronizing factors related to faster rates of stimulus
presentation in children with SLI
422. Bates E, Thal D, Finlay B, Clancy B. Early language development and its neural correlates.
In: Segalowitz S, Rapin I, editors. Child Neuropsychology. 2 ed. Amsterdam NL: Elsevier;
2003:525-572.
Ref ID: 4134
423. Bates E, Tager-Flusberg H, Vicari S, Volterra V. Debate over language's link with
intelligence. Nature 2001;413(6856):565-566.
Ref ID: 4411
424. Bates E, Vicari S, Trauner D. Neural mediation of language development: Perspectives
from lesion studies of infants and children. In: Tager-Flusberg H, editor. Neurodevelopmetal
disorders. Cambridge MA: MIT Press; 1999:533-581.
Ref ID: 2719
425. Bates E. Plasticity, localization and language development. In: Broman SH, Fletcher JM,
editors. The changing nervous system: Neurobehavioral consequences of early brain
development. New York: Oxford University Press; 1999:214-253.
Ref ID: 2823
426. Bates E, Marchman V, Thal D et al. Developmental and stylistic variation in the composition
of early vocabulary. J Child Lang 1994;21(1):85-123.
Ref ID: 5491
Abstract: Results are reported for stylistic and developmental aspects of vocabulary
composition for 1,803 children and families who participated in the tri-city norming of a new
parental report instrument, the MacArthur Communicative Development Inventories. We
replicate previous studies with small samples showing extensive variation in use of
common nouns between age 0; 8 and 1;4 (i.e. 'referential style'), and in the proportion of
vocabulary made up of closed-class words between 1;4 and 2;6 (i.e. 'analytic' vs. 'holistic'
style). However, both style dimensions are confounded with developmental changes in the
composition of the lexicon, including three 'waves' of reorganization: (I) an initial increase in
103
percentage of common nouns from 0 to 100 words, followed by a proportional decrease; (2)
a slow linear increase in verbs and other predicates, with the greatest gains taking place
between 100 and 400 words; (3) no proportional development at all in the use of
closed-class vocabulary between 0 and 400 words, followed by a sharp increase from 400
to 680 words. When developmental changes in noun use are controlled, referential-style
measures do not show the association with developmental precocity reported in previous
studies, although these scores are related to maternal education. By contrast, when
developmental changes in grammatical function word use are controlled, high closed-class
scores are associated with a slower rate of development. We suggest that younger children
may have less perceptual acuity and/or shorter memory spans than older children with the
same vocabulary size. As a result, the younger children may ignore unstressed function
words until a later point in development while the older children tend to reproduce
perceptual details that they do not yet understand. Longitudinal data show that early use of
function words (under 400 words) is not related to grammatical levels after the 400-word
point, confirming our 'stylistic' interpretation of early closed-class usage. We close with
recommendations for the unconfounding of stylistic and developmental variance in
research on individual differences in language development, and provide look-up tables
that will permit other investigators to pull these aspects apart
427. Bates E, Thal D, Janowsky JS. Early language development and its neural correlates. In:
Segalowitz SJ, Rapin I, editors. Section 10: Child Neuropsychology (Part 2). 1 ed.
Amsterdam NL: Elsevier Science; 1992:69-110.
Ref ID: 709
428. Bates E, Marchman VA. What is and is not universal in language acquisition. In: Plum F,
editor. Language, Communication, and the Brain. New York: Raven Press; 1992:19-38.
Ref ID: 1292
429. Bates E. Language development. Curr Opinion Neurobiol 1992;2(2):180-185.
Ref ID: 2616
Abstract: Recent research suggests that our ability to learn language is innate, but not
necessarily domain-specific. That is, language development appears to be based on a
relatively plastic mix of neural systems that also serve other cognitive and perceptual
functions. Evidence in support of this conclusion includes neural network simulations of
language learning, event-related brain potential studies of normal language development,
and studies of language development in several clinical populations of subjects suffering
focal brain injury, specific language impairment, and contrasting forms of mental
retardation. [References: 49]
430. Bates E. The Emergence of Symbols: Cognition and Communication in Infancy. New York:
Academic Press; 1979.
Ref ID: 943
431. Bateson G. A theory of play and fantasy. Psychiat Res Rep 1955;2:39-51.
Ref ID: 944
432. Bathgate D, Snowden JS, Varma A, Blackshaw A, Neary D. Behaviour in frontotemporal
dementia, Alzheimer's disease and vascular dementia. Acta Neurol Scand
2001;103(6):367-378.
Ref ID: 5878
Abstract: OBJECTIVES: The study aimed to increase understanding of behavioural
changes in frontotemporal dementia (FTD) and identify features that best differentiate FTD
from Alzheimer's disease (AD) and cerebrovascular dementia (CvD). METHODS: A
semi-structured questionnaire was administered to carers of 30 FTD, 75 AD and 34 CvD
patients. RESULTS: Behavioural changes that strongly discriminated FTD from AD and to
a lesser extent CvD were loss of emotions and insight, selfishness, disinhibition, personal
104
neglect, gluttony and sweet food preference, wandering, motor and verbal stereotypies,
loss of pain, echolalia and mutism. Irritability, hyposexuality and hypersomnia did not
discriminate. Emotional, eating and stereotyped behaviours correctly classified 95% of
patients using regression analysis. CONCLUSIONS: Behavioural characteristics accurately
differentiate FTD from AD and CvD. The findings highlight the particular importance of
affective change in FTD, and underline the role of the frontotemporal lobes in emotion
433. Battaglia A, Novelli A, Bernardini L, Igliozzi R, Parrini B. Further characterization of the new
microdeletion syndrome of 16p11.2-p12.2. Am J Med Genet A 2009;149A(6):1200-1204.
Ref ID: 6536
Abstract: Using aCGH, we have identified a pericentromeric deletion, spanning about 8.2
Mb, within 16p11.2-p12.2 in a patient with developmental delay (DD) and dysmorphic
features. This deletion arose de novo and is flanked by segmental duplications. The
proposita was the only child of healthy nonconsanguineous parents, born after an
uneventful pregnancy, at 40 weeks gestation, by normal delivery. She was referred to us at
age 3 10/12 years for evaluation of DD and absent speech. On examination, there were a
flat face; low-set, posteriorly rotated ears; high-arched palate; hypotonic face; right single
palmar crease; long, thin fingers; and a sacral dimple. Her height was at the 50th centile,
weight at the 25th, and OFC at the 30th. Results of DNA FraX, HRB chromosomes,
metabolic work-up, audiologic evaluation, brain MRI, electroencephalogram, and
heart/abdomen ultrasonography were normal. When last seen, aged 8 years, she had a
moderate intellectual disability (ID) and poor speech. She was hyperactive with short
attention span and difficulty in concentration, but, based on formal testing, did not have
autism. Our patient shows common clinical features to the four individuals described by
Ballif et al. [Ballif et al. (2007); Nat Genet 39:1071-1073], and further characterizes the new
microdeletion syndrome of 16p11.2-p12.2. aCGH suggests that the deletions of all cases
share the same distal breakpoint. Of note, the proximal breakpoint of our proposita
overlaps the distal breakpoint of the autistic patients studied by Kumar et al. [Kumar et al.
(2008); Hum Mol Genet 17:628-638] and Weiss et al. [Weiss et al. (2008); N Eng J Med
358:667-675], confirming that the 16p region carrying susceptibility to autism is more
centromeric. Our observation further defines two different, contiguous 16p genomic
regions, responsible for a distinct MCA/ID syndrome, and for autism, respectively
434. Battaglia A. On the selection of patients with developmental delay/mental retardation and
autism spectrum disorders for genetic studies. Am J Med Genet A 2007;143A(8):789-790.
Ref ID: 6541
435. Battaglia A, Carey JC. Etiologic yield of autistic spectrum disorders: a prospective study.
Am J Med Genet C Semin Med Genet 2006;142C(1):3-7.
Ref ID: 6530
Abstract: Studies addressing etiologic yield in childhood developmental disabilities have
mainly looked at individuals with developmental delay/mental retardation. The few studies
addressing the question of etiologic yield in patients with pervasive developmental
disorders (PDDs) had a major drawback, in that the enrolled subjects were diagnosed as
having the autistic spectrum disorders based only on history and clinical examination,
and/or on unspecified instruments. In addition, only some of these patients underwent a
complete laboratory evaluation. To investigate the etiologic yield of PDDs, we undertook a
large prospective study on subjects selected according to very strict criteria and diagnosed
as having PDD based on the present "gold standard" (ADI-R and ADOS-G), and a clinical
diagnosis made by a child psychiatrist. Eighty-five (85) patients with PDD and their first
degree relatives participated in this study. These patients were selected from a sample of
236 subjects who had received a clinical diagnosis of PDD at the Stella Maris Institute
between March 2002 and 2005. Selection criteria for entering the study were: (1) a
diagnosis of PDD (with exclusion of the Rett syndrome) confirmed after the administration
of the ADI-R (autism diagnostic interview-revised) and the ADOS-G (autism diagnostic
observation schedule-generic). In addition, a clinical diagnosis was made by the child
105
psychiatrist, on the basis of presence or absence of DSM-IV symptoms of autism; (2)
chronological age between 4 and 18 years; (3) IQ>30; (4) availability of both biologic
parents. Patients, 65/85 (76.5%), had autism, 18/85 (21.2%) had PDD-NOS, and the
remaining 2/85 (2.3%) had Asperger syndrome. Ages varied between 4 years 2 months
and 12 years 5 months (mean 7.6 years), and there was a marked male preponderance
(68/85). All subjects underwent various laboratory studies and neuroimaging. With respect
to possible etiologic determination, a detailed history and physical examination in this group
of patients with PDD was informative in 10.5% (9/85). HRB karyotype was diagnostic in
one, and molecular fragile X studies in one child. Brain MRI was informative in two children
(2.3%) with relative macrocrania but no neurological features; and EEG was helpful in one
child, identifying a Landau-Kleffner disorder. Audiometry and brainstem auditory evoked
potentials (BAEPs) showed a bilateral sensorineural loss in another child. Metabolic
evaluation gave normal results in all subjects. The results suggest an evaluation paradigm
with reference to etiologic determination for individuals with PDDs that does not presently
justify metabolic or neuroimaging on a screening basis. Recurrence risk, treatment
implications, and significant and long-lasting emotional relief for the parents suggest that
serious consideration be given to clinical genetic examination, genetic testing, EEG study
(during wakefulness and sleep), and audiometry, despite a relatively low yield
436. Battaglia A, Bonaglia MC. The yield of subtelomeric FISH analysis in the evaluation of
autistic spectrum disorders. Am J Med Genet C Semin Med Genet 2006;142C(1):8-12.
Ref ID: 6542
Abstract: To assess the frequency of cryptic subtelomeric rearrangements in children and
adolescents with autism spectrum disorders, blood samples were studied using a complete
set of subtelomeric FISH probes in 72 children with autism spectrum disorders. All children
had normal high resolution karyotype, DNA fra-X analysis, brain MRI, metabolic work-up,
and physical/neurological examination. Subtelomeric analysis did not detect abnormalities
in any of the subjects, suggesting the uselessness of such investigations in individuals with
primary autism spectrum disorders
437. Battaglia FP, Borensztajn G, Bod R. Structured cognition and neural systems: from rats to
language. Neurosci Biobehav Rev 2012;36(7):1626-1639.
Ref ID: 7807
Abstract: Much of animal and human cognition is compositional in nature: higher order,
complex representations are formed by (rule-governed) combination of more primitive
representations. We review here some of the evidence for compositionality in perception
and memory, motivating an approach that takes ideas and techniques from computational
linguistics to model aspects of structural representation in cognition. We summarize some
recent developments in our work that, on the one hand, use algorithms from computational
linguistics to model memory consolidation and the formation of semantic memory, and on
the other hand use insights from the neurobiology of memory to develop a neurally inspired
model of syntactic parsing that improves over existing (not cognitively motivated) models in
computational linguistics. These two theoretical studies highlight interesting analogies
between language acquisition, semantic memory and memory consolidation, and suggest
possible neural mechanisms, implemented in computational algorithms that may underlie
memory consolidation
438. Bauer PW, Sharma A, Martin K, Dorman M. Central auditory development in children with
bilateral cochlear implants. Arch Otolaryngol Head Neck Surg 2006;132(10):1133-1136.
Ref ID: 5571
Abstract: OBJECTIVE: To examine the time course of maturation of P1 latencies in infant
sequential and simultaneous bilateral cochlear implant recipients. DESIGN: Retrospective
case series. SETTING: Pediatric collaborative cochlear implant program. PATIENTS: Four
children who received bilateral cochlear implants prior to age 2 years. INTERVENTION:
Cortical auditory evoked potential was completed to determine the latency of the P1
response in 4 children with bilateral cochlear implants. MAIN OUTCOME MEASURES:
106
Longitudinal development of the latency of the P1 cortical auditory evoked potential in
children who received bilateral cochlear implants prior to age 2 years. RESULTS: In 2
patients who received sequential bilateral implants, P1 latencies recorded from the first
implanted ear were within normal limits after 3 to 6 months of implant use. By comparison,
P1 latencies from the second implanted ear reached normal limits as early as 1 month after
implant use. In 2 patients who received simultaneous bilateral implants, P1 latencies from
both ears were also within normal limits in a very short time frame (ie, by 1 month
poststimulation). CONCLUSIONS: Our data suggest a high degree of plasticity of the
central auditory pathways after early bilateral implantation. We find that P1 latencies
provide a clinically useful biomarker of central auditory system development in children
after cochlear implantation
439. Baujat G, Cormier-Daire V. Sotos syndrome. Orphanet J Rare Dis 2007;2:36.
Ref ID: 7422
Abstract: Sotos syndrome is an overgrowth condition characterized by cardinal features
including excessive growth during childhood, macrocephaly, distinctive facial gestalt and
various degrees of learning difficulty, and associated with variable minor features. The
exact prevalence remains unknown but hundreds of cases have been reported. The
diagnosis is usually suspected after birth because of excessive height and occipitofrontal
circumference (OFC), advanced bone age, neonatal complications including hypotonia and
feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include
scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes.
Variable delays in cognitive and motor development are also observed. The syndrome may
also be associated with an increased risk of tumors. Mutations and deletions of the NSD1
gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated
in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis,
MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and
direct sequencing allows detection of NSD1 mutations. The large majority of NSD1
abnormalities occur de novo and there are very few familial cases. Although most cases
are sporadic, several reports of autosomal dominant inheritance have been described.
Germline mosaicism has never been reported and the recurrence risk for normal parents is
very low (<1%). The main differential diagnoses are Weaver syndrome,
Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome
and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal
period, therapies are mostly symptomatic, including phototherapy in case of jaundice,
treatment of the feeding difficulties and gastroesophageal reflux, and detection and
treatment of hypoglycemia. General pediatric follow-up is important during the first years of
life to allow detection and management of clinical complications such as scoliosis and
febrile seizures. An adequate psychological and educational program with speech therapy
and motor stimulation plays an important role in the global development of the patients.
Final body height is difficult to predict but growth tends to normalize after puberty
440. Baulac S, Baulac M. Advances on the genetics of mendelian idiopathic epilepsies. Neurol
Clin 2009;27(4):1041-1061.
Ref ID: 7430
Abstract: Genetic factors play an increasingly recognized role in idiopathic epilepsies. Since
1995, positional cloning strategies in multi-generational families with autosomal dominant
transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4, CHRNA2, CHRNB2,
SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGI1) and numerous loci for febrile
seizures and epilepsies. To date, all genes with the exception of LGI1 (leucine-rich glioma
inactivated 1), encode neuronal ion channel or neurotransmitter receptor subunits.
Molecular approaches have revealed great genetic heterogeneity, with the vast majority of
genes remaining to be identified. One of the major challenges is now to understand
phenotype-genotype correlations. This review focuses on the current knowledge on the
molecular basis of these rare Mendelian autosomal dominant forms of idiopathic epilepsies
107
441. Bauman MD, Toscano JE, Babineau BA, Mason WA, Amaral DG. Emergence of
stereotypies in juvenile monkeys (Macaca mulatta) with neonatal amygdala or
hippocampus lesions. Behav Neurosci 2008;122(5):1005-1015.
Ref ID: 6105
Abstract: The emergence of stereotypies was examined in juvenile rhesus monkeys
(Macaca mulatta) who, at 2 weeks of postnatal age, received selective bilateral ibotenic
acid lesions of the amygdala (N = 8) or hippocampus (N = 8). The lesion groups were
compared to age-matched control subjects that received a sham surgical procedure (N =
8). All subjects were maternally reared for the first 6 months and provided access to social
groups throughout development. Pronounced stereotypies were not observed in any of the
experimental groups during the first year of life. However, between 1 to 2 years of age, both
amygdala- and hippocampus-lesioned subjects began to exhibit stereotypies. When
observed as juveniles, both amygdala- and hippocampus-lesioned subjects consistently
produced more stereotypies than the control subjects in a variety of contexts. More
interesting, neonatal lesions of either the amygdala or hippocampus resulted in unique
repertoires of repetitive behaviors. Amygdala-lesioned subjects exhibited more self-directed
stereotypies and the hippocampus-lesioned subjects displayed more head-twisting. We
discuss these results in relation to the neurobiological basis of repetitive stereotypies in
neurodevelopmental disorders, such as autism
442. Bauman MD, Lavenex P, Mason WA, Capitanio JP, Amaral DG. The development of social
behavior following neonatal amygdala lesions in rhesus monkeys. J Cogn Neurosci
2004;16(8):1388-1411.
Ref ID: 6651
Abstract: We examined the role of the amygdala in the development of nonhuman primate
social behavior. Twenty-four rhesus monkeys received bilateral ibotenic acid lesions of
either the amygdala or the hippocampus or received a sham surgical procedure at 2 weeks
of age. Subjects were reared with their mothers and were provided daily access to social
rearing cohorts. The subjects were weaned at 6 months of age and then observed while
paired with familiar conspecifics at 6 and 9 months of age and with unfamiliar conspecifics
at 1 year of age. The subjects were also observed during daily cohort socialization periods.
Neither amygdala nor hippocampus lesions altered fundamental aspects of social behavior
development. All subjects, regardless of lesion condition, developed a species-typical
repertoire of social behavior and displayed interest in conspecifics during social
encounters. The amygdala lesions, however, clearly affected behaviors related to fear
processing. The amygdala-lesioned subjects produced more fear behaviors during social
encounters than did control or hippocampus-lesioned subjects. Although the heightened
fear response of the amygdala-lesioned subjects was consistent across different testing
paradigms and was observed with both familiar and novel partners, it did not preclude
social interactions. In fact, the amygdala-lesioned subjects displayed particular social
behaviors, such as following, cooing, grunting, presenting to be groomed, and presenting to
be mounted more frequently than either control or hippocampus-lesioned subjects. These
findings are consistent with the view that the amygdala is not needed to develop
fundamental aspects of social behavior and may be more related to the detection and
avoidance of environmental dangers
443. Bauman MD, Lavenex P, Mason WA, Capitanio JP, Amaral DG. The development of
mother-infant interactions after neonatal amygdala lesions in rhesus monkeys. J Neurosci
2004;24(3):711-721.
Ref ID: 6652
Abstract: As part of ongoing studies on the neurobiology of socioemotional behavior in the
nonhuman primate, we examined the development of mother-infant interactions in 24
macaque monkeys who received either bilateral amygdala or hippocampus ibotenic acid
lesions, or a sham surgical procedure at 2 weeks of age. After surgery, the infants were
returned to their mothers and reared with daily access to small social groups. Behavioral
observations of the infants in dyads (mother-infant pairs alone), tetrads (two mother-infant
108
pairs), and social groups (six mother-infant pairs and one adult male) revealed
species-typical mother-infant interactions for all lesion conditions, with the exception of
increased physical contact time between the amygdala-lesioned infants and their mothers.
Immediately after permanent separation from their mothers at 6 months of age, the infants
were tested in a mother preference test that allowed the infants to choose between their
mother and another familiar adult female. Unlike control and hippocampus-lesioned infants,
the amygdala-lesioned infants did not preferentially seek proximity to their mother, nor did
they produce distress vocalizations. Given the normal development of mother-infant
interactions observed before weaning, we attribute the behavior of the amygdala-lesioned
infants during the preference test to an impaired ability to perceive potential danger (i.e.,
separation from their mother in a novel environment), rather than to a disruption of the
mother-infant relationship. These results are consistent with the view that the amygdala is
not essential for fundamental aspects of social behavior but is necessary to evaluate
potentially dangerous situations and to coordinate appropriate behavioral responses
444. Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and
future directions. Int J Dev Neurosci 2005;23(2-3):183-187.
Ref ID: 4643
Abstract: Infantile autism is a behaviorally defined disorder associated with characteristic
cognitive, language and behavioral features. Several postmortem studies have highlighted
areas of anatomic abnormality in the autistic brain. Consistent findings have been observed
in the limbic system, cerebellum and related inferior olive. In the limbic system, the
hippocampus, amygdala and entorhinal cortex have shown small cell size and increased
cell packing density at all ages, suggesting a pattern consistent with development
curtailment. Findings in the cerebellum have included significantly reduced numbers of
Purkinje cells, primarily in the posterior inferior regions of the hemispheres. A different
pattern of change has been noted in the vertical limb of the diagonal band of broca,
cerebellar nuclei and inferior olive with plentiful and abnormally enlarged neurons in the
brains of young autistic subjects, and in adult autistic brains, small, pale neurons that are
reduced in number. These findings combined with reported age-related changes in brain
weight and volume, have raised the possibility that the neuropathology of autism may
represent an on-going process
445. Bauman ML, Kemper TL. The neuropathology of the autism spectrum disorders: what have
we learned? Novartis Found Symp 2003;251:112-122.
Ref ID: 6492
Abstract: Autism is a behaviourally defined disorder, initially described by Kanner in 1943.
By definition, symptoms are manifested by 36 months of age and are characterized by
delayed and disordered language, impaired social interaction, abnormal responses to
sensory stimuli, events and objects, poor eye contact, an insistence on sameness, an
unusual capacity for rote memory, repetitive and stereotypic behaviour and a normal
physical appearance. Relatively few neuropathological studies have been performed on the
brains of autistic subjects. Of those reported, abnormalities have been described in the
cerebral cortex, the brainstem, the limbic system and the cerebellum. Although those with
the disorder present with a specific set of core characteristics, each individual patient is
somewhat different from another. Thus, it should not be surprising that the brains of these
subjects should show a wide range of abnormalities. However, it is important to delineate
the anatomic features, which are common to all cases, regardless of age, sex and IQ, in
order to begin to understand the central neurobiological profile of this disorder. The results
of our systematic studies indicate that the anatomic features that are consistently abnormal
in all cases include reduced numbers of Purkinje cells in the cerebellum, and small tightly
packed neurons in the entorhinal cortex and in the medially placed nuclei of the amygdala.
It is known that the limbic system is important for learning and memory, and that the
amygdala plays a role in emotion and behaviour. Research in the cerebellum indicates that
this structure is important as a modulator of a variety of brain functions and impacts on
language processing, anticipatory and motor planning, mental imagery and timed
109
sequencing. Defining the differences and similarities in brain anatomy in autism and
correlating these observations with detailed clinical descriptions of the patient may allow us
greater insight into the underlying neurobiology of this disorder
446. Bauman ML. The neuroanatomy of autism: Clinical implications. In: Accardo PJ, Shapiro
BK, Capute AJ, editors. Behavior Belongs in the Brain: Neurobehavioral Syndromes.
Baltimore MD: York Press; 1997:69-95.
Ref ID: 1665
447. Bauman ML, Kemper TL. Is autism a progressive process? Neurology , A285. 1997.
Ref Type: Abstract
Ref ID: 1923
448. Bauman ML, Filipek PA, Kemper TL. Early infantile autism. Int Rev Neurobiol
1997;41:367-386.
Ref ID: 3906
449. Bauman ML, Kemper TL. Observations on the Purkinje cells in the cerebellar vermis in
autism. Journal of Neuropathology and Experimental Neurology 55, 613. 1996.
Ref Type: Abstract
Ref ID: 1924
450. Bauman ML. Brief report: neuroanatomic observations of the brain in pervasive
developmental disorders. J Autism Dev Disord 1996;26(2):199-203.
Ref ID: 3907
451. Bauman ML, Kemper TL, Arin DM. Pervasive neuroanatomic abnormalities of the brain in
three cases of Rett's syndrome. Neurology 1995;45(8):1581-1586.
Ref ID: 3909
Abstract: Rett's syndrome (RS) is a clinically defined disorder that appears to be unique to
girls and is characterized by apparent cognitive and motor skill loss early in life. We report
our findings in the brains of three girls with RS, which were studied in comparison with
age-matched controls by means of gapless serial section. Reduced neuronal cell size and
increased cell-packing density were present throughout the cortical and subcortical regions
of the brain in all cases without evidence of active degeneration. These observations
appear to be consistent with a curtailment of development. Further, the degree of
abnormality in each case correlates more closely with the clinical presentation of the patient
at the time of death than with the age of the patient or duration of symptoms
452. Bauman ML, Kemper TL, editors. The Neurobiology of Autism. Baltimore MD: The Johns
Hopkins University Press; 1994.
Ref ID: 326
453. Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism. In: Bauman
ML, Kemper TL, editors. The neurobiology of autism. Baltimore, MD: The Johns Hopkins
University Press; 1994:119-145.
Ref ID: 946
454. Bauman ML. Motor dysfunction in autism. In: Joseph AB, Young RR, editors. Movement
Disorders in Neurology and Neuropsychiatry. Boston,MA: Blackwell; 1992:660-663.
Ref ID: 1328
455. Bauman ML. Neuropathology of autism. In: Joseph AB, Young RR, editors. Movement
Disorders in Neurology and Neuropsychiatry. Boston,MA: Blackwell; 1992:664-668.
Ref ID: 1334
110
456. Bauman ML. Microscopic neuroanatomic abnormalities in autism. Pediatrics
1991;87(5):571-796.
Ref ID: 911
457. Bauman ML, Kemper TL. Histoanatomic observations of the brain in early infantile autism.
Neurology 1985;35:866-874.
Ref ID: 120
458. Baumeister AA, Forehand R. Stereotyped acts. In: Ellis NR, editor. Internationlal Review of
Research in Mental Retardation. New York: Academic Press; 1973:55-96.
Ref ID: 1528
459. Baumgaertel A, Wolraich ML, Dietrich M. Comparison of diagnositic criteria for attention
deficit disorders in a German elementary school sample. J Am Acad Child Adolesc
Psychiatry 1995;34:629-638.
Ref ID: 1433
460. Bava S, Ballantyne AO, Trauner DA. Disparity of verbal and performance IQ following early
bilateral brain damage. Cogn Behav Neurol 2005;18(3):163-170.
Ref ID: 7288
Abstract: OBJECTIVE: To examine the effects of early bilateral brain damage on Full Scale
IQ (FSIQ), Verbal IQ (VIQ) and Performance IQ (PIQ). BACKGROUND: Early unilateral
brain damage typically results in relatively spared intellectual function, with IQ in the normal
range and no significant differences between VIQ and PIQ, regardless of the side of the
lesion. However, little is known about intellectual function in children after bilateral damage.
METHOD: FSIQ, VIQ, and PIQ scores of 10 children, ages 6-12 years, with early-onset
bilateral focal lesions (BFL), were compared with those of age- and sex-matched controls.
RESULTS: FSIQ was in the average range for BFL and control children. A bimodal
distribution of VIQ was identified, resulting in 2 distinct groups, one performing above the
average range and the other below. The unimpaired group displayed a significant
discrepancy between VIQ and PIQ, with VIQ in the superior range and PIQ in the low
average range. The impaired group did not demonstrate disparate VIQ and PIQ: both were
in the borderline range. The 2 groups were differentiated by greater degree of cortical brain
damage in the impaired than in the unimpaired group. CONCLUSIONS: The striking
difference between the outcome of the unimpaired and impaired groups may reflect
different processes of reorganization that are associated with the extent of cortical
involvement
461. Bavelier D, Tomann A, Hutton C et al. Visual attention to the periphery is enhanced in
congenitally deaf individuals. J Neurosci 2000;20(17):RC93.
Ref ID: 4154
Abstract: We compared normally hearing individuals and congenitally deaf individuals as
they monitored moving stimuli either in the periphery or in the center of the visual field.
When participants monitored the peripheral visual field, greater recruitment (as measured
by functional magnetic resonance imaging) of the motion-selective area MT/MST was
observed in deaf than in hearing individuals, whereas the two groups were comparable
when attending to the central visual field. This finding indicates an enhancement of visual
attention to peripheral visual space in deaf individuals. Structural equation modeling was
used to further characterize the nature of this plastic change in the deaf. The effective
connectivity between MT/MST and the posterior parietal cortex was stronger in deaf than in
hearing individuals during peripheral but not central attention. Thus, enhanced peripheral
attention to moving stimuli in the deaf may be mediated by alterations of the connectivity
between MT/MST and the parietal cortex, one of the primary centers for spatial
representation and attention
111
462. Bavelier D, Jezzard P, Clark V et al. Hemispheric specialization for English and ASL: left
invariance-right variability. Neuroreport 1998;9(7):1537-1542.
Ref ID: 2734
Abstract: Functional magnetic resonance imaging (fMRI) was used to compare the cerebral
organization during sentence processing in English and in American sign language (ASL).
Classical language areas within the left hemisphere were recruited by both English in
native speakers and ASL in native signers. This suggests a bias of the left hemisphere to
process natural languages independently of the modality through which language is
perceived. Furthermore, in contrast to English, ASL strongly recruited right hemisphere
structures. This was true irrespective of whether the native signers were deaf or hearing.
Thus, the specific processing requirements of the language also in part determine the
organization of the language systems of the brain
463. Bavelier D, Corina DP, Neville HJ. Brain and language: a perspective from sign language.
Neuron 1998;21(2):275-278.
Ref ID: 2756
464. Bayley N. Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). 3rd
ed. San Antonio TX: Harcourt; 2005.
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465. Bayley N. Bayley Scales of Infant Development. 2 ed. San Antonio TX: Psychological
Corporation; 1993.
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466. Bayley N. Bayley Scales of Infant Development. 1 ed. San Antonio, TX: Psychological
Corporation; 1969.
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467. Bazelon, E. What autistic girls are made of. New York Times 2007;Magazine(Aug. 5, 2007).
Ref ID: 5335
468. Beadle EA, McKinley DJ, Nikolopoulos TP, Brough J, O'Donoghue GM, Archbold SM.
Long-term functional outcomes and academic-occupational status in implanted children
after 10 to 14 years of cochlear implant use. Otol Neurotol 2005;26(6):1152-1160.
Ref ID: 6415
Abstract: OBJECTIVES: To assess a group of consecutively implanted children over 10
years after implantation with regard to implant device use and function, speech perception,
and speech intelligibility outcomes; and to document current academic or occupational
status. STUDY DESIGN: A prospective longitudinal study assessing device function, device
use, speech perception, speech intelligibility, and academic/occupational status of
implanted deaf children. SETTING: Pediatric tertiary referral center for cochlear
implantation. METHODS: The auditory performance and speech intelligibility development
of 30 profoundly deaf children were rated before cochlear implantation and at 5 and 10
years after implantation using the Categories of Auditory Performance and the Speech
Intelligibility Rating. The academic and/or occupational status of the participants after 10
years of implant experience was documented. All children received a Nucleus multichannel
cochlear implant between the ages of 2.5 and 11 years (mean age at implantation, 5.2 yr).
Implant experience ranged from 10 to 14 years of use. RESULTS: After 10 years of implant
experience, 26 subjects (87%) reported that they always wore their device; 2 subjects (7%),
frequently; and 1 subject (3%), occasionally. Only one child had discontinued use of his
device. After 10 years of implant use, 26 (87%) of the children understood a conversation
without lip reading and 18 (60%) used the telephone with a familiar speaker. Ten years
after implantation, 23 (77%) of the subjects used speech intelligible to an average listener
or a listener with little experience of a deaf person's speech. One-third to one-half of the
implanted children continued to demonstrate improvements at 5 to 10 years of implant use.
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Of the 30 implanted children, 8 (26.7%) experienced nine device failures. The length of
time from identification of the first faulty electrode to reimplant surgery ranged from 2 weeks
to 5.5 years, as several failures were gradual or intermittent. However, all children were
successfully reimplanted. At the end of the study (10-14 yr after implantation), 19 subjects
were in secondary school for children aged 11 to 16 years: 6 were in mainstream schools,
7 were in specialist hearing-impaired units attached to a mainstream secondary school, and
6 were in schools for the deaf. Of the remaining 11 subjects, 4 were in college studying
vocational subjects, 2 were in a university studying for a bachelor's degree, 3 were working
full-time, 1 was working and going to a university part-time, and 1 was a full-time mother of
two young children. CONCLUSION: All but 1 of the 30 implanted children continue using
their devices 10 to 14 years after implantation, showing significant progress in speech
perception and production. Device failure was frequent, but successful reimplantation
occurred in all cases. One-third to one-half of the implanted children in this study continued
to demonstrate improvements at 5 to 10 years of implant use. All children are studying or
working and are actively involved in their local communities. The results suggest that
cochlear implantation provides long-term communication benefit to profoundly deaf children
that does not plateau for some subjects even after reimplantation. This study further
indicates that cochlear implant centers need the structure and funding to provide long-term
support, counseling, audiologic follow-up, rehabilitation, and device monitoring to implanted
children
469. Bear MF, Dolen G, Osterweil E, Nagarajan N. Fragile X: translation in action.
Neuropsychopharmacology 2008;33(1):84-87.
Ref ID: 5577
Abstract: Fragile X is a synapsopathy--a disorder of synaptic function and plasticity. Recent
studies using mouse models of the disease suggest that the critical defect is altered
regulation of synaptic protein synthesis. Various strategies to restore balanced synaptic
protein synthesis have been remarkably successful in correcting widely varied mutant
phenotypes in mice. Insights gained by the study of synaptic plasticity in animal models of
fragile X have suggested novel therapeutic approaches, not only for human fragile X but
also for autism and mental retardation of unknown etiology
470. Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children
with skin disease and children with other chronic childhood diseases. Br J Dermatol
2006;155(1):145-151.
Ref ID: 4996
Abstract: BACKGROUND: Chronic disease can have physical and psychological effects
which affect social functioning. These effects can be better understood from the
perspective of parent and child by the use of health-related quality of life (HRQL)
measures. Various HRQL measures are now available, of which generic health measures
have been the most widely used. These permit comparison between different diseases and
also the normal population. OBJECTIVES: To cross-validate a new generic HRQL proxy
measure for children, the Children's Life Quality Index (CLQI), with an established
speciality-specific dermatological questionnaire, the Children's Dermatology Life Quality
Index (CDLQI), in a group of children with chronic skin diseases. The impairment of HRQL
in the same group of children with skin disease was then compared with that associated
with other common chronic childhood diseases using the CLQI. METHODS: The CDLQI
was completed by 379 children aged 5-16 years with skin disease of more than 6 months'
duration. Their parents (n=379) and parents of 161 children aged 5-16 years with other
chronic diseases were also asked to complete a proxy measure, the CLQI. RESULTS:
Using linear regression analysis, the CLQI and the CDLQI scores showed a strong linear
association (rs=0.72, P<0.001) and on a Bland-Altman plot, reasonably good agreement
(expressing scores out of 100, the 95% limits of agreement were from -25.5/100 to
26.7/100). In the child's opinion psoriasis and atopic dermatitis (AD) caused the greatest
impairment (CDLQI scores of 30.6% and 30.5%), followed by urticaria (20%) and acne
(18%). Using the generic CLQI (scored 0-36), from the parental perspective the highest
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score was for AD (33%), followed by urticaria (28%), psoriasis (27%) and alopecia (19%).
Comparing this with children with other chronic diseases, those with cerebral palsy had the
highest score (38%), followed in descending order by those with generalized AD (33%),
renal disease (33%), cystic fibrosis (32%), urticaria (28%), asthma (28%) and psoriasis
(27%). Diseases such as epilepsy (24%) and enuresis (24%) scored higher than diabetes
(19%), localized eczema (19%), alopecia (19%) and acne (16%). CONCLUSIONS: Using
the CLQI we have shown that HRQL impairment in children with chronic skin disease is at
least equal to that experienced by children with many other chronic diseases of childhood,
with AD and psoriasis having the greatest impact on HRQL among chronic skin disorders
and only cerebral palsy scoring higher than AD. Cross-validation of the CLQI with the
CDLQI in the group of children with skin disease demonstrates a strong linear association
and good agreement between the two
471. Beauchaine TP. Taxometrics and developmental psychopathology. Dev Psychopathol
2003;15(3):501-527.
Ref ID: 4487
Abstract: Developmental psychopathologists have criticized categorical classification
systems for their inability to account for within-group heterogeneity in biological, etiological.
developmental, and cultural influences on behavior. Dichotomizing continuous scores of
symptom severity is also inadvisable statistically. Perhaps because of a resulting wariness
of categorizing, few explorations into the ontological status of traits or disorders as
dimensional versus discrete have been conducted. It is argued here that the limitations of
categorizing have little to do with the ontological status of traits and that developmental
psychopathologists should be concerned with identifying discrete behavioral syndromes.
Common taxometric methods for resolving discrete traits are described, and questions of
concern to developmental psychopathologists are outlined that can be addressed through
taxometrics studies. These include (a) identifying children who are at risk for future
psychopathology, (b) identifying discrete subtypes within current diagnostic classes, (c)
locating sensitive periods in the development of discrete pathological traits, (d) discovering
moderators of treatment outcome, and (e) elucidating mechanisms of equifinality and
multifinality. Although most behavioral traits probably are distributed continuously,
identifying those that are discrete will advance the science of developmental
psychopathology. Disorders for which taxometric analyses might be applied include
anxiety, attention deficit hyperactivity disorder, autism spectrum disorders, conduct
problems, depression, and schizophrenia
472. Beaucousin V, Lacheret A, Turbelin MR, Morel M, Mazoyer B, Tzourio-Mazoyer N. FMRI
study of emotional speech comprehension. Cereb Cortex 2007;17(2):339-352.
Ref ID: 5933
Abstract: Little is known about the neural correlates of affective prosody in the context of
affective semantic discourse. We used functional magnetic resonance imaging to
investigate this issue while subjects performed 1) affective classification of sentences
having an affective semantic content and 2) grammatical classification of sentences with
neutral semantic content. Sentences of each type were produced half by actors and half by
a text-to-speech software lacking affective prosody. Compared with neutral sentences
processing, sentences with affective semantic content--with or without affective
prosody--led to an increase in activation of a left inferior frontal area involved in the retrieval
of semantic knowledge. In addition, the posterior part of the left superior temporal sulcus
(STS) together with the medial prefrontal cortex were recruited, although not activated by
neutral sentences classification. Interestingly, these areas have been described as
implicated during self-reflection or other's mental state inference that possibly occurred
during the affective classification task. When affective prosody was present, additional
rightward activations of the human-selective voice area and the posterior part of STS were
observed, corresponding to the processing of speaker's voice emotional content. Accurate
affective communication, central to social interactions, requires the cooperation of
semantics, affective prosody, and mind-reading neural networks
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473. Beaudet AL. Autism: highly heritable but not inherited. The genetic basis of autism is
beginning to come to light. De novo mutations in gene copynumber may have a big role.
Nat Med 2007;13(5):534-536.
Ref ID: 5178
474. Beaudet AL. Complex imprinting. Nat Genet 2004;36(8):793-795.
Ref ID: 4311
475. Beaudet AL. Is medical genetics neglecting epigenetics? Genet Med 2002;4(5):399-402.
Ref ID: 4316
476. Beaudet AL, Jiang YH. A rheostat model for a rapid and reversible form of
imprinting-dependent evolution. Am J Hum Genet 2002;70(6):1389-1397.
Ref ID: 4317
Abstract: The evolutionary advantages of genomic imprinting are puzzling. We propose that
genomic imprinting evolved as a mechanism that maximizes the interindividual variability in
the rates of gene expression for dosage-sensitive loci that, with minimal unrelated
deleterious effects, can alter the phenotype over a wide continuum. We hypothesize (1)
that genomic imprinting provides a previously suggested haploid selective advantage
(HSA); (2) that many imprinted genes have evolved mechanisms that facilitate quantitative
hypervariability (QH) of gene expression; (3) that the combination of HSA and QH makes
possible a rapid and reversible form of imprinting-dependent evolution (IDE) that can
mediate changes in phenotype; and (4) that this enhanced adaptability to a changing
environment provides selective advantage to the population, as an assisted form of
evolution. These mechanisms may have provided at least one of the driving forces for the
evolution of genomic imprinting in mammals. The rheostat model suggests that both
genetic and epigenetic variants can contribute to an integrated mechanism of mixed
Mendelian and non-Mendelian inheritance and suggests the possibility that the majority of
variants are not intrinsically deleterious but, depending on the environment, are each
potentially advantageous. Moreover, this would be a reversible form of evolution, with the
ability not only to protect a silent allele from selection for many generations but to reactivate
and expand it in the population quickly
477. Beaudet AL, Scriver CR, Sly WS, Valle D. Genetics, biochemistry, and molecular bases of
variant human phenotypes. In: Valle D, Beaudet AL, Vogelstein B, Antonarakis SE, Ballabio
A, editors. Scriver's Metabolic and Molecular Bases of Human Disease. New York, N.Y.:
McGraw-Hill; 2001:3-45.
Ref ID: 5655
478. Beaumanoir A. The Landau-Kleffner syndrome. In: Roger J, Dravet C, Bureau M, Dreifuss
FE, Wolf P, editors. Epileptic Syndromes in Infancy, Childhood and Adolescence. London
UK: John Libbey Eurotext; 1985:181-191.
Ref ID: 254
479. Beauregard M, Bachevalier J. Neonatal insult to the hippocampal region and
schizophrenia: a review and a putative animal model. [Review] [145 refs]. Canadian Journal
of Psychiatry - Revue Canadienne de Psychiatrie 1996;41(7):446-456.
Ref ID: 2423
Abstract: OBJECTIVE: To review the mounting evidence implicating early hippocampal
dysfunction in the pathogenesis and the pathophysiology of schizophrenia. An account is
made of recent neurodevelopmental hypotheses indicating how an early dysfunction of the
hippocampal region disrupts maturational events in brain systems connected to that
structure, thus inducing dysfunctional connectional development. Finally, an animal model
is presented. METHOD: Socioemotional behaviour of monkeys (Macaca mulatta) with
selective neonatal hippocampal lesions was assessed by analyzing their interactions with
their age-matched controls at 2 months, 6 months, and 5 to 8 years of age and by
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comparing the social interactions at each age with those of normal controls paired together.
RESULTS: At 2 months of age, monkeys with neonatal hippocampal lesions presented
minor disturbances in initiation of social interactions. These subtle changes of behaviour
were less evident at 6 months, although by that age, the operated monkeys displayed more
withdrawals in response to an increase in aggressive responses from their unoperated
peers. In adulthood, the amount of time spent by the hippocampectomized monkeys in
social contacts with their normal peers decreased markedly. In addition, operated monkeys
exhibited more locomotor stereotypies than normal controls. CONCLUSION: These
experimental findings indicate that the time-course and nature of the behavioural
disturbances resulting from early trauma to the hippocampal region have some similarities
with the clinical symptoms of schizophrenic patients and the typical time-course of the
disease. [References: 145]
480. Beck J, Rohrer JD, Campbell T et al. A distinct clinical, neuropsychological and radiological
phenotype is associated with progranulin gene mutations in a large UK series. Brain
2008;131(Pt 3):706-720.
Ref ID: 5869
Abstract: Mutations in the progranulin gene (GRN) are a major cause of frontotemporal
lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) but the
distinguishing clinical and anatomical features of this subgroup remain unclear. In a large
UK cohort we found five different frameshift and premature termination mutations likely to
be causative of FTLD in 25 affected family members. A previously described 4-bp insertion
mutation in GRN exon 2 comprised the majority of cases in our cohort (20/25), with four
novel mutations being identified in the other five affected members. Additional novel
missense changes were discovered, of uncertain pathogenicity, but deletion of the entire
gene was not detected. The patient collection was investigated by a single tertiary referral
centre and is enriched for familial early onset FTLD with a high proportion of patients
undergoing neuropsychological testing, MRI and eventual neuropathological diagnosis. Age
at onset was variable, but four mutation carriers presented in their 40s and when analysed
as a group, the mean age at onset of disease in GRN mutation carriers was later than tau
gene (MAPT) mutation carriers and duration of disease was shorter when compared with
both MAPT and FTLD-U without mutation. The most common clinical presentation seen in
GRN mutation carriers was behavioural variant FTLD with apathy as the dominant feature.
However, many patients had language output impairment that was either a progressive
non-fluent aphasia or decreased speech output consistent with a dynamic aphasia.
Neurological and neuropsychological examination also suggests that parietal lobe
dysfunction is a characteristic feature of GRN mutation and differentiates this group from
other patients with FTLD. MR imaging showed evidence of strikingly asymmetrical atrophy
with the frontal, temporal and parietal lobes all affected. Both right- and left-sided
predominant atrophy was seen even within the same family. As a group, the GRN carriers
showed more asymmetry than in other FTLD groups. All pathologically investigated cases
showed extensive type 3 TDP-43-positive pathology, including frequent neuronal
cytoplasmic inclusions, dystrophic neurites in both grey and white matter and also neuronal
intranuclear inclusions. Finally, we confirmed a modifying effect of APOE-E4 genotype on
clinical phenotype with a later onset in the GRN carriers suggesting that this gene has
distinct phenotypic effects in different neurodegenerative diseases
481. Beckel-Mitchener A, Greenough WT. Correlates across the structural, functional, and
molecular phenotypes of fragile X syndrome. Ment Retard Dev Disabil Res Rev
2004;10(1):53-59.
Ref ID: 5636
Abstract: Fragile X syndrome (FXS) is characterized by a pattern of morphological,
functional, and molecular characteristics with, in at least some cases, apparent
relationships among phenotypic features at different levels. Gross morphology differences
in the sizes of some human brain regions are accompanied by fine structural alterations in
the shapes and in the numbers of dendritic spines in both humans and the knockout mouse
116
model. The excess number of spines, their immature appearance, and the impaired
withdrawal of inappropriately oriented dendrites in FXS or the mouse model suggest
impairment of neuronal maturation, including dendritic and spine pruning. It is not clear how
these differences arise, although regionally or globally impaired translation of the mRNAs
that interact with the Fmr1 protein product, FMRP, in the vicinity of the synapse, including
genes involved in synapse development and plasticity and dendritic retraction, is certainly
plausible. FMRP binds mRNA and may be involved in both transport and translation of the
mRNAs it binds. The mRNAs it binds belong to multiple functional classes, apparently
indicating that FMRP may impact multiple cellular processes. In one example, the
glucocorticoid receptor, whose mRNA binds FMRP, regulates the stress-sensitive
glucocorticosteroids. Both human FXS and the mouse model exhibit a protracted elevation
in glucocorticosteroids after stress. Possible relationships of other genes to morphological
and functional characteristics of FXS are also discussed
482. Becker PS, Dixon AM, Troncoso JC. Bilateral opercular polymicrogyria. Ann Neurol
1989;25:90-92.
Ref ID: 1619
483. Beckett C, Castle J, Rutter M, Sonuga-Barke EJ. VI. Institutional deprivation, specific
cognitive functions, and scholastic achievement: English and Romanian Adoptee (ERA)
study findings. Monogr Soc Res Child Dev 2010;75(1):125-142.
Ref ID: 6967
484. Beckett C, Bredenkamp D, Castle J, Groothues C, O'Connor TG, Rutter M. Behavior
patterns associated with institutional deprivation: a study of children adopted from
Romania. J Dev Behav Pediatr 2002;23(5):297-303.
Ref ID: 3977
Abstract: This study examined the prevalence and persistence of behaviors associated with
institutional rearing in a sample of 144 children from Romania adopted by UK families.
Patterns of rocking, self-injury, unusual sensory interests, and eating problems were
assessed in children aged between a few weeks and 43 months who were adopted from
institutional care. Forty-seven percent of the institutionally reared children rocked at the
time of UK entry and 24% engaged in self-injurious behavior. By age 6 years, the
percentages were 18% and 13%, respectively. Eleven percent of the children were
displaying unusual sensory interests at the time of arrival, and at 6 years 13% of the
children did so. Fifteen percent of the children were still experiencing difficulties with
chewing and swallowing solid food at age 6 years. The primary factor affecting the
prevalence and persistence of the behaviors was the length of time the children had spent
in institutional deprivation
485. Bedny M, Saxe R. Insights into the origins of knowledge from the cognitive neuroscience of
blindness. Cogn Neuropsychol 2012;29(1-2):56-84.
Ref ID: 7683
Abstract: Children learn about the world through senses such as touch, smell, vision, and
audition, but they conceive of the world in terms of objects, events, agents, and their mental
states. A fundamental question in cognitive science is how nature and nurture contribute to
the development of such conceptual categories. What innate mechanisms do children bring
to the learning problem? How does experience contribute to development? In this article we
discuss insights into these longstanding questions from cognitive neuroscience studies of
blindness. Despite drastically different sensory experiences, behavioural and
neuroscientific work suggests that blind children acquire typical concepts of objects,
actions, and mental states. Blind people think and talk about these categories in ways that
are similar to sighted people. Neuroimaging reveals that blind people make such
judgements relying on the same neural mechanisms as sighted people. One way to
interpret these findings is that neurocognitive development is largely hardwired, and so
differences in experience have little consequence. Contrary to this interpretation,
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neuroimaging studies also show that blindness profoundly reorganizes the visual system.
Most strikingly, developmental blindness enables "visual" circuits to participate in high-level
cognitive functions, including language processing. Thus, blindness qualitatively changes
sensory representations, but leaves conceptual representations largely unchanged. The
effect of sensory experience on concepts is modest, despite the brain's potential for
neuroplasticity
486. Bedny M, Pascual-Leone A, Dodell-Feder D, Fedorenko E, Saxe R. Language processing
in the occipital cortex of congenitally blind adults. Proc Natl Acad Sci U S A
2011;108(11):4429-4434.
Ref ID: 7684
Abstract: Humans are thought to have evolved brain regions in the left frontal and temporal
cortex that are uniquely capable of language processing. However, congenitally blind
individuals also activate the visual cortex in some verbal tasks. We provide evidence that
this visual cortex activity in fact reflects language processing. We find that in congenitally
blind individuals, the left visual cortex behaves similarly to classic language regions: (i)
BOLD signal is higher during sentence comprehension than during linguistically degraded
control conditions that are more difficult; (ii) BOLD signal is modulated by phonological
information, lexical semantic information, and sentence-level combinatorial structure; and
(iii) functional connectivity with language regions in the left prefrontal cortex and thalamus
are increased relative to sighted individuals. We conclude that brain regions that are
thought to have evolved for vision can take on language processing as a result of early
experience. Innate microcircuit properties are not necessary for a brain region to become
involved in language processing
487. Bedny M, Pascual-Leone A, Saxe RR. Growing up blind does not change the neural bases
of Theory of Mind. Proc Natl Acad Sci U S A 2009;106(27):11312-11317.
Ref ID: 7685
Abstract: Humans reason about the mental states of others; this capacity is called Theory
of Mind (ToM). In typically developing adults, ToM is supported by a consistent group of
brain regions: the bilateral temporoparietal junction (TPJ), medial prefrontal cortex (MPFC),
precuneus (PC), and anterior temporal sulci (aSTS). How experience and intrinsic
biological factors interact to produce this adult functional profile is not known. In the current
study we investigate the role of visual experience in the development of the ToM network
by studying congenitally blind adults. In experiment 1, participants listened to stories and
answered true/false questions about them. The stories were either about mental or physical
representations of reality (e.g., photographs). In experiment 2, participants listened to
stories about people's beliefs based on seeing or hearing; people's bodily sensations (e.g.,
hunger); and control stories without people. Participants judged whether each story had
positive or negative valance. We find that ToM brain regions of sighted and congenitally
blind adults are similarly localized and functionally specific. In congenitally blind adults,
reasoning about mental states leads to activity in bilateral TPJ, MPFC, PC, and aSTS.
These brain regions responded more to passages about beliefs than passages about
nonbelief representations or passages about bodily sensations. Reasoning about mental
states that are based on seeing is furthermore similar in congenitally blind and sighted
individuals. Despite their different developmental experience, congenitally blind adults have
a typical ToM network. We conclude that the development of neural mechanisms for ToM
depends on innate factors and on experiences represented at an abstract level, amodally
488. Bedny M, Hulbert JC, Thompson-Schill SL. Understanding words in context: the role of
Broca's area in word comprehension
14. Brain Res 2007;1146:101-114.
Ref ID: 7686
Abstract: What role does meaning selection play in word comprehension, and what neural
systems support this selection process? Most words have multiple meanings and are
therefore ambiguous. This is true of both homonymous words (words that have multiple
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unrelated meanings) and polysemous words (words that have multiple related meanings).
The extant evidence indicates that meaning selection is an integral part of homonym
comprehension. However, it is not known whether meaning selection extends to
polysemous words, or what neural systems support meaning selection during
comprehension. Prior neuroimaging and neuropsychological evidence suggest that the left
inferior frontal gyrus (LIFG) may play a role in resolving competition during language
processing. We therefore sought to test the hypotheses that meaning selection is part of
polysemous word comprehension, and that the LIFG resolves meaning competition during
word comprehension. We tested healthy participants on a version of the triplet lexical
decision task, with polysemous and homonymous stimuli. Results suggest that the
meanings of polysemous words, like the meanings of homonyms, are selected based on
context. However, homonymous and polysemous words differed in how meaning frequency
affected meaning selection. We then administered the triplet lexical decision task to
patients with LIFG damage to examine whether this region plays a role in
context-dependent meaning selection. Results support the hypothesis that the LIFG serves
as a top-down biasing mechanism that facilitates rapid meaning selection during word
comprehension. We conclude that context-dependent meaning selection is an integral part
of word comprehension for both homonyms and polysemous words, and that the LIFG
facilitates this selection process
489. Bedogni F, Hodge RD, Nelson BR et al. Autism susceptibility candidate 2 (Auts2) encodes
a nuclear protein expressed in developing brain regions implicated in autism
neuropathology. Gene Expr Patterns 2009.
Ref ID: 6482
Abstract: Autism susceptibility candidate 2 (Auts2) is a gene associated with autism and
mental retardation, whose function is unknown. Expression of Auts2 mRNA and protein
were studied in the developing mouse brain by in situ hybridization, immunohistochemistry,
and western blotting. Auts2 mRNA was highly expressed in the developing cerebral cortex
and cerebellum, regions often affected by neuropathological changes in autism, and a few
other brain regions. On embryonic day (E) 12, Auts2 mRNA was expressed in the cortical
preplate, where it colocalized with Tbr1, a transcription factor specific for postmitotic
projection neurons. From E16 to postnatal day 21, Auts2 was expressed most abundantly
in frontal cortex, hippocampus and cerebellum, including Purkinje cells and deep nuclei.
High levels of Auts2 were also detected in developing dorsal thalamus, olfactory bulb,
inferior colliculus and substantia nigra. Auts2 protein showed similar regional expression
patterns as the mRNA. At the cellular level, Auts2 protein was localized in the nuclei of
neurons and some neuronal progenitors
490. Beery K. Beery-Buktenica Test of Visual-Motor Integration (4th Edition). 4th ed. Parsippany
NJ: Modern Curriculum Press; 1997.
Ref ID: 4599
491. Befi-Lopes DM, Silva CP, Bento AC. Semantic representation and naming in children with
specific language impairment. Pro Fono 2010;22(2):113-118.
Ref ID: 6922
Abstract: BACKGROUND: children with Specific Language Impairment (SLI) show lexical
deficits as the first noticeable sign of such disorder, characterized as difficulties in lexical
access during naming and speech tests. Studies that compare picture naming and
drawings seem perfect to clarify lexical deficits. AIM: to compare the performance of
children with normal language development (NLD) to that of children with SLI in naming,
drawing and definition tasks, aiming to explore the the quality of semantic representation of
the lexicon. METHOD: Two groups were involved in this study: the Control Group (CG),
with no language disorders, composed by 40 subjects, and the Research Group (RG), with
20 subjects, all diagnosed with SLI, aging from five to seven years. Tasks of naming,
picture drawing and definition were performed, using 20 different pictures. In the naming
task, the types of errors were analyzed and sorted as follows: semantic, phonological, none
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specified and others. The analysis of the drawing and definition tasks was based only on
the correct answers, semantic and none specified errors. RESULTS: children of the RG
presented a greater number of semantic errors in the picture naming task when compared
to the CG. Besides that, definitions presented by the RG seemed more simple and
incomplete even when the child was capable of naming the picture correctly. Drawings of
correctly named objects were better than those that were named incorrectly.
CONCLUSIONS: it was possible to discriminate within SLI children those that present
greater lexical deficits. It was also possible to explore the possible reasons for failures in
naming tasks
492. Behrmann M, Avidan G, Leonard GL, Kimchi R, Luna B, Humphreys KMN. Configural
processing in autism and its relationship to face processing. Neuropsychologia
2006;44:110-129.
Ref ID: 4835
Abstract: Studies of the perceptual performance of individuals with autism have focused, to
a large extent, on two domains of visual behavior, one associated with face processing and
the other associated with global or holistic processing. Whether autistic individuals differ
from neurotypical individuals in these domains is debatable and, moreover, the relationship
between the behaviors in these two domains remains unclear. We first compared the face
processing ability of 14 adult individuals with autism with that of neurotypical controls and
showed that the autistic individuals were slowed in their speed of face discrimination. We
then showed that the two groups differed in their ability to derive the global whole in two
different tasks, one using hierarchical compound letters and the other using a microgenetic
primed matching task with geometric shapes, with the autistic group showing a bias in favor
of local information. A significant correlation was also observed between performance on
the face task and the configural tasks. We then confirmed the prediction that the ability to
derive the global whole is not only critical for faces but also for other objects as well, as the
autistic individuals performed more slowly than the control group in discriminating between
objects. Taken together, the results suggest that the bias for local processing seen in
autistic individuals might have an adverse impact on their ability to process faces and
objects
493. Beisler JM, Tsai LY, Vonk D. comparison between autistic and nonautistic children on the
Test for the Auditory Comprehension of Language. J Autism Dev Disord
1987;17(1):95-102.
Ref ID: 3563
494. Beitchman JH, Brownlie EB, Inglis A et al. Seven-year follow-up of speech/language
impaired and control children: psychiatric outcome. J Child Psychol Psychiatry
1996;37(8):961-970.
Ref ID: 2578
Abstract: This study examined the 7-year psychiatric outcome of 202 speech/language
(S/L) impaired and control children selected from a community sample at age 5 years.
Children with S/L at age 5 years were more likely to be psychiatric cases at age 12.5 years
than were normal controls, even if their S/L improved. Controlling for concurrent psychiatric
disorder, S/L impairment at age 5 years was still associated with an increased rate of
psychiatric disorder at 12.5 years. Psychiatric disorder at age 12.5 years was more likely to
co-occur with language disorder than with speech disorder
495. Beitchman JH, Wilson B, Brownlie EB, Walters H, Lancee W. Long-term consistency in
speech/language profiles: I. Developmental and academic outcomes. Journal of the
American Academy of Child & Adolescent Psychiatry 1996;35(6):804-814.
Ref ID: 2586
Abstract: OBJECTIVE: This study examined the 7-year developmental and academic
outcome of speech/language-impaired and control children selected from a community
sample. METHOD: Speech/language and psychiatric measures were administered to the
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children at ages 5 and 12.5 years. Using children's age 5 speech/language test results, a
cluster analysis was performed to ascertain whether specific linguistic subgroups would
emerge. The long-term consistency of these subgroups was explored. The association
between time 1 speech/language clusters and linguistic, cognitive and academic measures
at time 2 were examined. RESULTS: Four groups were identified in the cluster analysis:
high overall, poor articulation, poor comprehension, and low overall. Children with
pervasive language problems continued to perform poorly on linguistic, cognitive, and
academic measures, while those with comprehension problems fared slightly better but still
had more difficulties than those with normal language. The poor articulation cluster had few
articulation errors at follow-up. CONCLUSIONS: Empirically supported speech/language
classifications identified as early as age 5 continued to be relevant into late childhood.
Pervasive speech/language impairment in early childhood was associated with increased
risk of poor linguistic and academic outcome at follow-up, while isolated articulatory
problems improved over time. These findings reveal the urgent need for early intervention
among children with pervasive speech/language impairment
496. Beitchman JH, Wilson B, Brownlie EB, Walters H, Inglis A, Lancee W. Long-term
consistency in speech/language profiles: II. Behavioral, emotional, and social outcomes.
Journal of the American Academy of Child & Adolescent Psychiatry 1996;35(6):815-825.
Ref ID: 2587
Abstract: OBJECTIVE: This study examined the 7-year behavioral, emotional, and social
outcome of speech/language-impaired and control children selected from a community
sample. METHOD: Speech/language and psychosocial measures were administered to the
children at ages 5 and 12.5 years. Using children's age 5 speech/language test results, a
cluster analysis was performed to ascertain whether specific linguistic subgroups would
emerge. The association between speech/language cluster at age 5 and psychosocial
functioning at age 12.5 was examined. RESULTS: Children with receptive and pervasive
speech/language problems at age 5 demonstrated greater behavioral disturbance than
children without such impairment. Controlling for initial behavioral status, early childhood
language profile was still associated with behavioral and social competence ratings, 7
years later. Children without receptive language problems showed superior social
adjustment. CONCLUSIONS: Empirically supported speech/language classifications
identified as early as age 5 were associated with behavioral disturbance in late childhood.
Receptive and pervasive speech/language impairment in early childhood was associated
with the greatest risk at follow-up. Early auditory comprehension problems may be a
specific risk factor for later aggressive and hyperactive symptoms. These findings identify
the need for effective intervention with speech/language-impaired children
497. Beitchman JH, Inglis A. The continuum of linguistic dysfunction from pervasive
developmental disorders to dyslexia. Psychiatr Clin North Am 1991;14(1):95-111.
Ref ID: 3422
Abstract: This article examines speech and language impairment in relation to several
common childhood psychiatric disorders. Similarities among disorders can be found in the
associated language impairments, family histories, and certain language outcomes. The
article describes prevalence surveys of speech and language disorders and the correlates
of language impairment, such as IQ, socioeconomic status, and birth order. The
association between language impairment and childhood psychiatric disorders (i.e.,
hyperactivity, autism) is investigated, and the outcomes of language impairment are
discussed. Finally, the hypothesis that a common underlying neurolinguistic diathesis may
be present for certain subgroups of psychiatrically disordered children is presented. In
some groups, psychiatric disorder (i.e., hyperactivity) and linguistic impairment may
develop in parallel as a function of an underlying neurodevelopmental immaturity. The
relation between the linguistic impairment and neurodevelopmental immaturity requires
clarification so as to disentangle their specific associations with the various disorders
discussed
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498. Beitchman JH, Hood J, Rochon J, Peterson M. Empirical classification of speech/language
impairment in children. II. Behavioral characteristics. Journal of the American Academy of
Child and Adolescent Psychiatry 1989;28(1):118-123.
Ref ID: 3204
499. Beitchman JH, Hood J, Rochon J, Peterson M, Mantini T, Majumdar S. Empirical
classification of speech/language impairment in children: I. Identification of
speech/language categories. Journal of the American Academy of Child and Adolescent
Psychiatry 1989;28(1):112-117.
Ref ID: 5035
500. Beitchman JH, Peterson M, Clegg M. Speech and language impairment and psychiatric
disorder: The relevance of family demographic variables. Child Psychiatry Hum Dev
1988;18:191-207.
Ref ID: 1310
501. Beitchman JH, Tuckett M, Batth S. Language delay and hyperactivity in preschoolers:
Evidence for a distinct group of hyperactives. Can J Psychiatry 1987;32:683-687.
Ref ID: 921
502. Beitchman JH, Nair R, Clegg M, Patel PG. Prevalence of speech and language disorders in
5-year-old kindergarten children in the Ottawa-Carleton region. J Speech Hear Disord
1986;51:98-110.
Ref ID: 919
503. Beitchman JH, Nair R, Clegg M, Ferguson B, Patel PG. Prevalence of psychiatric disorders
in children with speech and language disorders. J Am Acad Child Psychiatry
1986;25:528-535.
Ref ID: 1254
504. Belinchon-Carmona M, Posada-De la Paz M, Artigas-Pallares J et al. [Best practice
guidelines for research in autistic spectrum disorders]. Rev Neurol 2005;41(6):371-377.
Ref ID: 6549
Abstract: INTRODUCTION: Achieving a better knowledge of autism and other pervasive
developmental disorders known as autistic spectrum disorders (ASD), poses a major
scientific challenge. These disorders are some of the earliest and most severe
psychopathological disorders in infancy; they include an heterogeneous group of
conditions; its prevalence rate seems to be continually increasing and they generate a
significant social impact. AIMS AND DEVELOPMENT: Nowadays, there is a current
international agreement on the general requirements to be fulfilled by research projects and
the priority areas to be considered when developing ASD high quality research. In Spain,
although there are some established research groups with broad experience and expertise
in these disorders, public funding opportunities and research development are still scarce.
For this reason, the Study Group of the Instituto de Salud Carlos III has generated by
consensus some Good Practice Guidelines for Research in ASD. CONCLUSIONS: After
comparing priorities and recommendations from international reference documents with the
results obtained after having carried out an exhaustive bibliographic revision of articles
published in autism in the last 30 years by Spanish authors, methodological and ethical
recommendations are established. Finally, structural deficiencies to be corrected and
emerging research initiatives to be supported are identified
505. Bell WL, Davis DL, Morgan-Fisher A, Ross ED. Acquired aprosodia in children. J Child
Neurol 1990;5(1):19-26.
Ref ID: 9
Abstract: In adults, the affective components of language, including certain aspects of
prosody and gesturing, appear to be a dominant function of the right hemisphere. The
122
various combinations of affective processing deficits associated with focal right brain
damage are called aprosodias and have functional and anatomical correlates similar to the
propositional language deficits associated with aphasias secondary to focal left brain
damage. Developmental affective-prosodic deficits have been reported recently in children
with congenital or very early right hemisphere injury. We now report two school-aged
children with acquired motor-type aprosodias following acute right focal brain injury. Their
affective prosody and singing were also analyzed acoustically during the acute and
recovery phases of illness. Based on these cases, we propose the term children aprosodia
to describe affective-prosodic deficits that result from acquired lesions of the right
hemisphere in children
506. Belliveau JW, Kwong KK, Kennedy DN et al. Magnetic resonance imaging mapping of brain
function. Human visual cortex. Invest Radiol 1992;27 Suppl 2:S59-S65.
Ref ID: 7786
Abstract: Magnetic resonance imaging (MRI) studies of human brain activity are described.
Task-induced changes in brain cognitive state were measured using high-speed MRI
techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and
blood oxygenation. These techniques were used to generate the first functional MRI maps
of human task activation, by using a visual stimulus paradigm. The methodology of MRI
brain mapping and results from the investigation of the functional organization and
frequency response of human primary visual cortex (V1) are presented
507. Belliveau JW, Kennedy DN, Jr., McKinstry RC et al. Functional mapping of the human
visual cortex by magnetic resonance imagingS. Science 1991;254(5032):716-719.
Ref ID: 7787
Abstract: Knowledge of regional cerebral hemodynamics has widespread application for
both physiological research and clinical assessment because of the well-established
interrelation between physiological function, energy metabolism, and localized blood
supply. A magnetic resonance technique was developed for quantitative imaging of
cerebral hemodynamics, allowing for measurement of regional cerebral blood volume
during resting and activated cognitive states. This technique was used to generate the first
functional magnetic resonance maps of human task activation, by using a visual stimulus
paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent,
n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and
linear extents of brain activation within the plane of the calcarine fissure are reported
508. Bellugi U, St.George M. Journey from cognition to brain to gene: perspectives from
Williams syndrome. Cambridge MA: MIT Press; 2001.
Ref ID: 4249
509. Bellugi U, Lichtenberger L, Mills D, Galaburda A, Korenberg JR. Bridging cognition, the
brain and molecular genetics: evidence from Williams syndrome. TINS
1999;22(5):197-207.
Ref ID: 2817
Abstract: Williams syndrome (WMS) is a rare sporadic disorder that yields a distinctive
profile of medical, cognitive, neurophysiological, neuroanatomical and genetic
characteristics. The cognitive hallmark of WMS is a dissociation between language and
face processing (relative strengths) and spatial cognition (profound impairment). Individuals
with WMS also tend to be overly social, behavior that is opposite to that seen in autism. A
genetic hallmark of WMS is a deletion on chromosome band 7q11.23. Williams syndrome
is also associated with specific neuromorphological and neurophysiological profiles:
proportional sparing of frontal, limbic and neocerebellar structures is seen using MRI; and
abnormal functional organization of the neural systems that underlie both language and
face processing is revealed through studies using event-related potentials. The
non-uniformity in the cognitive, neuromorphological and neurophysiological domains of
123
WMS make it a compelling model for elucidating the relationships between cognition, the
brain and, ultimately, the genes. [References: 82]
510. Bellugi U, Klima ES, Poizner H. Sign language and the brain. Research Publications Association for Research in Nervous & Mental Disease 1988;66:39-56.
Ref ID: 2747
Abstract: Analysis of the patterns of breakdown of a visuospatial language in deaf signers
thus allows new perspectives on the nature and determinants of cerebral specialization for
language. First, these data show that hearing and speech are not necessary for the
development of hemispheric specialization--sound is not crucial. Second, the data show
that in these deaf signers, it is the left hemisphere that is dominant for sign language. The
patients with damage to the left hemisphere showed marked sign language deficits but
relatively intact capacity for processing nonlanguage visuospatial relations. The patients
with damage to the right hemisphere showed much the reverse pattern. Thus, not only is
there left hemisphere specialization for language functioning, there is a complementary
right hemisphere specialization for visuospatial functioning. The fact that much of the
grammatical information is conveyed via spatial manipulation appears not to alter this
complementary specialization. Furthermore, the finding that components of sign language
(e.g., lexicon and grammar) can be selectively impaired suggests that the functional
organization of the brain for sign language may turn out to be modular. Finally, patients with
left and right hemisphere damage showed dissociations between two uses of space in the
language--one to represent spatial relations and the other to represent syntactic relations.
Right hemisphere damage disrupts the former but spares the latter; left hemisphere
damage disrupts the use of space for syntactic relations but spares its use for spatial
relations. Taken together with studies of the processing of sign language "on line" by
neurologically intact deaf signers, these data suggest that the left cerebral hemisphere in
humans may have an innate predisposition for language, independent of language
modality. Studies of the effects of brain damage on signing make it clear that accounts of
hemispheric specialization are oversimplified if stated only in terms of a dichotomy between
language and visuospatial functioning. Such studies may also permit us to come closer to
the real principles underlying the specializations of the two cerebral hemispheres, since in
sign language there is interplay between visuospatial and linguistic relations within the
same system
511. Belman AL, Lantos G, Horoupian D et al. AIDS: calcification of the basal ganglia in infants
and children. Neurology 1986;36(9):1192-1199.
Ref ID: 5929
512. Belmonte MK, Mazziotta JC, Minshew NJ et al. Offering to share: how to put heads
together in autism neuroimaging. J Autism Dev Disord 2007;38(1):2-13.
Ref ID: 5170
Abstract: Data sharing in autism neuroimaging presents scientific, technical, and social
obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with
other measures of phenotype and with genetics, defines requirements for comparability of
derived data and recommendations for raw data, outlines a core protocol including
multispectral structural and diffusion-tensor imaging and optional extensions, provides for
the collection of prospective, confound-free normative data, and extends sharing and
collaborative development not only to data but to the analytical tools and methods applied
to these data. A theme in these requirements is the need to preserve creative approaches
and risk-taking within individual laboratories at the same time as common standards are
provided for these laboratories to build on
513. Belmonte MK, Bourgeron T. Fragile X syndrome and autism at the intersection of genetic
and neural networks. Nat Neurosci 2006;9(10):1221-1225.
Ref ID: 4938
Abstract: Autism, an entirely behavioral diagnosis with no largely understood etiologies and
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no population-wide biomarkers, contrasts with fragile X syndrome (FXS), a single-gene
disorder with definite alterations of gene expression and neuronal morphology.
Nevertheless, the behavioral overlap between autism and FXS suggests some overlapping
mechanisms. Understanding how the single-gene alteration in FXS plays out within
complex genetic and neural network processes may suggest targets for autism research
and illustrate strategies for relating autism to more singular genetic syndromes
514. Belmonte MK, Cook EH, Jr., Anderson GM et al. Autism as a disorder of neural information
processing: directions for research and targets for therapy. Mol Psychiatry
2004;9(7):646-663.
Ref ID: 4887
Abstract: The broad variation in phenotypes and severities within autism spectrum
disorders suggests the involvement of multiple predisposing factors, interacting in complex
ways with normal developmental courses and gradients. Identification of these factors, and
the common developmental path into which they feed, is hampered by the large degrees of
convergence from causal factors to altered brain development, and divergence from
abnormal brain development into altered cognition and behaviour. Genetic, neurochemical,
neuroimaging, and behavioural findings on autism, as well as studies of normal
development and of genetic syndromes that share symptoms with autism, offer hypotheses
as to the nature of causal factors and their possible effects on the structure and dynamics
of neural systems. Such alterations in neural properties may in turn perturb
activity-dependent development, giving rise to a complex behavioural syndrome many
steps removed from the root causes. Animal models based on genetic, neurochemical,
neurophysiological, and behavioural manipulations offer the possibility of exploring these
developmental processes in detail, as do human studies addressing endophenotypes
beyond the diagnosis itself
515. Belmonte MK, Allen G, Beckel-Mitchener A, Boulanger LM, Carper RA, Webb SJ. Autism
and abnormal development of brain connectivity. J Neurosci 2004;24(42):9228-9231.
Ref ID: 5460
516. Belsito KM, Law PA, Kirk KS, Landa RJ, Zimmerman AW. Lamotrigine therapy for autistic
disorder: a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord
2001;31(2):175-181.
Ref ID: 4011
Abstract: In autism, glutamate may be increased or its receptors up-regulated as part of an
excitotoxic process that damages neural networks and subsequently contributes to
behavioral and cognitive deficits seen in the disorder. This was a double-blind,
placebo-controlled, parallel group study of lamotrigine, an agent that modulates glutamate
release. Twenty-eight children (27 boys) ages 3 to 11 years (M = 5.8) with a primary
diagnosis of autistic disorder received either placebo or lamotrigine twice daily. In children
on lamotrigine, the drug was titrated upward over 8 weeks to reach a mean maintenance
dose of 5.0 mg/kg per day. This dose was then maintained for 4 weeks. Following
maintenance evaluations, the drug was tapered down over 2 weeks. The trial ended with a
4-week drug-free period. Outcome measures included improvements in severity and
behavioral features of autistic disorder (stereotypies, lethargy, irritability, hyperactivity,
emotional reciprocity, sharing pleasures) and improvements in language and
communication, socialization, and daily living skills noted after 12 weeks (the end of a
4-week maintenance phase). We did not find any significant differences in improvements
between lamotrigine or placebo groups on the Autism Behavior Checklist, the Aberrant
Behavior Checklist, the Vineland Adaptive Behavior scales, the PL-ADOS, or the CARS.
Parent rating scales showed marked improvements, presumably due to expectations of
benefits
125
517. Belsky J, Most RK. From exploration to play: A cross-sectional study of infant free play
behavior. Dev Psychol 1981;17:630-639.
Ref ID: 1224
518. Belton E, Salmond CH, Watkins KE, Vargha-Khadem F, Gadian DG. Bilateral brain
abnormalities associated with dominantly inherited verbal and orofacial dyspraxia. Hum
Brain Mapp 2003;18(3):194-200.
Ref ID: 3881
Abstract: The KE family is a large three-generational pedigree in which half of the members
suffer from a verbal and orofacial dyspraxia in association with a point mutation in the
FOXP2 gene. This report extends previous voxel-based morphometric analyses of
magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a
bilateral conjunction analysis. This searches specifically for areas of grey matter density
that differ bilaterally in the affected members compared with both matched controls and the
unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10
affected, 7 unaffected) and matched controls were compared. The most significant findings
were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and
the left and right inferior frontal gyrus in the affected members. In addition, increased grey
matter density was found bilaterally in the planum temporale. These results confirm that a
point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in
both motor and language related regions. The results also demonstrate the advantages of
using a conjunction analysis when bilateral abnormalities are suspected
519. Belyantseva IA, Boger ET, Naz S et al. Myosin-XVa is required for tip localization of whirlin
and differential elongation of hair-cell stereocilia. Nat Cell Biol 2005;7(2):148-156.
Ref ID: 6292
Abstract: Stereocilia are microvilli-derived mechanosensory organelles that are arranged in
rows of graded heights on the apical surface of inner-ear hair cells. The 'staircase'-like
architecture of stereocilia bundles is necessary to detect sound and head movement, and is
achieved through differential elongation of the actin core of each stereocilium to a
predetermined length. Abnormally short stereocilia bundles that have a diminished
staircase are characteristic of the shaker 2 (Myo15a(sh2)) and whirler (Whrn(wi)) strains of
deaf mice. We show that myosin-XVa is a motor protein that, in vivo, interacts with the third
PDZ domain of whirlin through its carboxy-terminal PDZ-ligand. Myosin-XVa then delivers
whirlin to the tips of stereocilia. Moreover, if green fluorescent protein (GFP)-Myo15a is
transfected into hair cells of Myo15a(sh2) mice, the wild-type pattern of hair bundles is
restored by recruitment of endogenous whirlin to the tips of stereocilia. The interaction of
myosin-XVa and whirlin is therefore a key event in hair-bundle morphogenesis
520. Belyantseva IA, Labay V, Boger ET, Griffith AJ, Friedman TB. Stereocilia: the long and the
short of it. Trends Mol Med 2003;9(11):458-461.
Ref ID: 6294
Abstract: Mutations in whirlin, a putative PDZ scaffold protein, have recently been shown to
cause deafness and short cochlear hair cell stereocilia in whirler mice and recessive
deafness (DFNB31) in humans. Through its PDZ domains, whirlin might organize a group
of proteins into a functional complex required for stereocilia elongation. Identifying these
protein partners will advance our understanding of the development of stereocilia and their
function as mechanosensory organelles indispensable for normal hearing
521. Ben-Artsy A. An assessment of hemineglect in children with attention-deficit hyperactivity
disorder. Dev Neuropsychol 1996;12(3).
Ref ID: 2555
Abstract: Examined evidence produced by K. K. Voeller and K. M. Heilman (1988)
suggesting a right-hemisphere dysfunction associated with attention-deficit hyperactivity
disorder (ADHD): ADHD-related hemineglect. The present study is a constructive
replication, using carefully screened children (aged 7-10.5 yrs) with ADHD for a number of
126
compromising factors (e.g., no lateralized brain damage, handedness, eyedness). Each
child received 2 tests: Line Bisection and Visual Target Cancellation Test. In addition, their
performance was assessed in both binocular and monocular viewing conditions. While the
ADHD children performed generally worse than the controls on target cancellation (i.e.,
exhibiting higher inattention), there was no evidence for hemineglect. To complicate
matters, a reversed right-left imbalance was tapped using a structured task array for this
test, for left-eye dominant ADHD children not on medication. Besides drawing attention to
the role of the dominant eye in the scanning of children with ADHD, it is suggested that no
firm conclusions regarding an ostensible ADHD-related hemineglect may be drawn. ((c)
1997 APA/PsycINFO, all rights reserved)
522. Ben-Sasson A, Carter AS, Briggs-Gowan MJ. The development of sensory
over-responsivity from infancy to elementary school. J Abnorm Child Psychol
2010;38(8):1193-1202.
Ref ID: 6753
Abstract: Some infants experience atypical levels of over-responsivity to sensations, which
limit their ability to interact and explore their environment. Yet, little is known about typical
development of over-responsivity during infancy or whether the presence of extreme
over-responsivity in infancy is a predictor of clinically significant sensory over-responsivity
(SOR) at school-age. This study followed a representative sample of children (n = 521,
47% boys) at four time points from infancy (mean ages in months Year 1 = 18.23, Year 2 =
30.39, Year 3 = 39.40) to elementary school-age (mean age = 7.97 years). SOR was
measured via parent report. A latent growth curve model predicting SOR at school age
from the intercept and slope of Sensory Sensitivity between Years 1-3 showed excellent fit
with the data. Both early sensory sensitivities and change in early sensitivities were
associated with SOR status at school-age
523. Ben-Sasson A, Cermak SA, Orsmond GI et al. Extreme sensory modulation behaviors in
toddlers with autism spectrum disorders. Am J Occup Ther 2007;61(5):584-592.
Ref ID: 6755
Abstract: This study examined the incidence of extreme sensory modulation behaviors in
toddlers with autism spectrum disorders (ASD) and investigated the consistency of sensory
information across measures. Parent report of sensory behaviors in 101 toddlers with ASD
was compared with 100 toddlers who were typically developing matched on chronological
age and 99 additional infants or toddlers matched on mental age. Measures included the
Infant/Toddler Sensory Profile, Infant-Toddler Social Emotional Assessment, Autism
Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule-Generic.
Toddlers with ASD were most distinct from typically developing groups in their high
frequency of underresponsiveness and avoiding behaviors and their low frequency of
seeking. Within the toddlers with ASD, there were significant associations across sensory
parent report measures, but parent report was not correlated with clinical observation.
Findings point to the early onset of an extreme sensory profile in ASD. Occupational
therapists need to assess multiple domains of sensory behaviors to accurately identify the
needs of toddlers with ASD
524. Ben Bashat D, Kronfeld-Duenias V, Zachor DA et al. Accelerated maturation of white
matter in young children with autism: A high b value DWI study. NeuroImage 2007.
Ref ID: 5083
Abstract: The goal of this work was to study white matter maturation in young children with
autism following previous reports of increased cerebral volume during early development,
as well as arguments for abnormal neural growth patterns and regulation at this critical
developmental period. We applied diffusion tensor imaging (DTI) and high b value
diffusion-weighted imaging (DWI) to young children diagnosed with autism and to a
typically developing (TD) control group. Fractional anisotropy (FA), probability and
displacement were measured in overall analysis as well as in regions of interest (ROI).
Individual data points of children with autism were compared to the developmental curves
127
obtained from typically developing children. Increased restriction, reflected in significantly
increased FA and probability along with reduced displacement values, was detected in
overall analysis as well as in several brain regions. Increased restriction, suggesting an
early and accelerated abnormal maturation of white matter, was more dominant in the left
hemisphere and was mainly detected in the frontal lobe. No changes were detected in the
occipital lobes. These results support previous claims of abnormal brain overgrowth in
young children with autism and are in contrast to the decreased restricted diffusion reported
in previous studies in adolescent with autism
525. Ben Shalom D. Memory in autism: review and synthesis. Cortex 2003;39(4-5):1129-1138.
Ref ID: 3910
Abstract: Much research about memory in autism concerns the hypothesis that autism is
similar to adult-onset amnesia. Initial support for the hypothesis came from post-mortem
studies of individuals with autism showing abnormalities in the hippocampus and related
brain structures, as well as behavioral studies finding contrasts between intact cued recall
and impaired free recall and recognition in autism. The hypothesis was later brought into
question by the finding of intact performance in individuals with autism on explicit memory
tasks typically impaired in adult-onset amnesia. The present paper proposes a possible
reconciliation of these contradictory findings, suggesting that there is selective damage to
the limbic-prefrontal episodic memory system, sparing the limbic-only perceptual
representation system, and the semantic memory system. This view is consistent with other
evidence for early selective damage to other systems involving cooperation between the
limbic system and the medial prefrontal cortex in autism
526. Ben Zeev GB. Rett syndrome. Child Adolesc Psychiatr Clin N Am 2007;16(3):723-743.
Ref ID: 5084
Abstract: Rett syndrome (RS) is an X-linked neurodevelopmental disorder and the second
most common cause of genetic mental retardation in females. Different mutations in
MECP2 are found in up to 95% of typical cases of RS. This mainly neuronal expressed
gene functions as a major transcription repressor. Extensive studies on girls who have RS
and mouse models are aimed at finding main gene targets for MeCP2 protein and defining
neuropathologic changes caused by its defects. Studies comparing autistic features in RS
with idiopathic autism and mentally retarded patients are presented. Decreased dendritic
arborization is common to RS and autism, leading to further research on similarities in
pathogenesis, including MeCP2 protein levels in autistic brains and MeCP2 effects on
genes connected to autism, like DLX5 and genes on 15q11-13 region. This area also is
involved in Angelman syndrome, which has many similarities to RS. Despite these
connections, MECP2 mutations in nonspecific autistic and mentally retarded populations
are rare
527. Benarroch EE. Neocortical interneurons: Functional diversity and clinical correlations.
Neurology 2013;81(3):273-280.
Ref ID: 7688
Abstract: The cerebral cortex contains 2 types of neurons: principal (mostly pyramidal)
neurons, which constitute approximately 80% of the total population, and local
interneurons, which constitute approximately 20% of the total population, with some
species variation. Pyramidal cells are excitatory glutamatergic neurons that participate in
cortico-cortical connections or project to subcortical areas. Local interneurons utilize
gamma-aminobutyric acid (GABA) as their primary neurotransmitter and participate in local
circuits in the cerebral cortex. Normal sensory perception, attention, and planning and
execution of behaviors depend on interactions among canonical neocortical circuits
involving excitatory and inhibitory neurons. Cortical interneurons have a fundamental role in
shaping cortical circuits and controlling neocortical network interactions. These
interneurons form functionally distinct networks that are temporally coordinated by electrical
coupling via gap junctions, and establish GABAergic synapses not only with pyramidal
neurons but also among each other. Via these interactions, GABAergic interneurons control
128
the timing of pyramidal cell firing, generation of cortical rhythms, organization of sensory
fields, and cortical plasticity. Impaired activity of neocortical inhibitory interneurons has
been associated with several neurologic and psychiatric disorders, including epilepsy,
mental retardation, schizophrenia, and autism. There are many comprehensive reviews on
GABAergic interneuron heterogeneity, development, plasticity, function in shaping cortical
activity, and involvement in disease.(1-13.)
528. Benarroch EE. Oligodendrocytes: Susceptibility to injury and involvement in neurologic
disease. Neurology 2009;72(20):1779-1785.
Ref ID: 6097
529. Benarroch EE. Brain iron homeostasis and neurodegenerative disease. Neurology
2009;72(16):1436-1440.
Ref ID: 6098
530. Benarroch EE. Enteric nervous system: functional organization and neurologic implications.
Neurology 2007;69(20):1953-1957.
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531. Benda CE. Developmental disorders of mentationand cerebral palsies. New York: Grune
and Stratton; 1952.
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532. Bender L. Childhood schizophrenia: A clinical study of 100 schizophrenic children. Journal
of Orthopsychiatry 1947;17:40-56.
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533. Bender L. Childhood schizophrenia: A clinical study of 100 schizophrenic children. Am J
Orthopsychiatry 1947;17:40-56.
Ref ID: 930
534. Bennett FC, Ruuska SH, Sherman R. Middle ear function in learning disabled children.
Pediatrics 1980;66:254-260.
Ref ID: 817
535. Bennett KE, Haggard MP. Behaviour and cognitive outcomes from middle ear disease.
Arch Dis Child 1999;80(1):28-35.
Ref ID: 2761
Abstract: OBJECTIVES: To resolve controversies over associations between a history of
middle ear disease and psychosocial or cognitive/educational outcomes. DESIGN:
Multipurpose longitudinal birth cohort study. Original cohort comprised all UK births
between 5 and 11 April 1970; data were available for approximately 12,000 children at 5
years old and 9000 children at 10 years old. METHODS: For 5 year old children, parent
reported data were available on health, social, and behavioural factors, including data on
two validated markers of middle ear disease. Cognitive tests were administered at 5 and 10
years of age, and behavioural problems rated at 10 years by the child's teacher. RESULTS:
After adjustment for social background and maternal malaise, the developmental sequelae
of middle ear disease remained significant even at 10 years. The largest effects were
observed in behaviour problems and language test data at age 5, but effect sizes were
modest overall. IMPLICATIONS: These results provide an epidemiological basis for policies
that aim to minimise the sequelae of middle ear disease by awareness in parents and
preschool teachers, early referral, and intervention for more serious or persistent cases
536. Bennett T, Szatmari P, Bryson S et al. Differentiating Autism and Asperger Syndrome on
the Basis of Language Delay or Impairment. J Autism Dev Disord 2007.
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Ref ID: 5344
Abstract: Asperger syndrome (AS) is differentiated from high-functioning autism (HFA)
largely on a history of "language delay." This study examined "specific language
impairment" as a predictor of outcome. Language skills of 19 children with AS and 45 with
HFA were assessed at 4-6 years of age (Time 1) and 2 years later (Time 2). Children's
symptoms and functional outcome scores were assessed every 2 years (Times 3, 4, and 5)
until ages 15-17 years old. Regression analysis revealed that specific language impairment
at time 2 more often accounted for the greatest variation in outcome scores in adolescence
than the standard diagnosis of AS versus HFA based on history of language delay.
Diagnostic implications are discussed
537. Bennetto L, Kuschner ES, Hyman SL. Olfaction and taste processing in autism. Biol
Psychiatry 2007;62(9):1015-1021.
Ref ID: 5082
Abstract: BACKGROUND: Autism is often associated with sensory symptoms, but few
studies have examined chemosensory functions in this population. We examined olfactory
and taste functioning in individuals with autism to characterize chemosensory processing
and test competing hypotheses about underlying brainstem versus cortical abnormalities.
METHODS: Twenty-one participants (10-18 years) with autism were compared with 27
well-matched control participants with typical development. Taste identification was tested
via sucrose, NaCl, citric acid, and quinine solutions applied to standard locations on the
anterior tongue. Taste detection thresholds were established in the same regions with
electrogustometry, and olfactory identification was evaluated with "Sniffin' Sticks."
RESULTS: Participants with autism were significantly less accurate than control
participants in identifying sour tastes and marginally less accurate for bitter tastes, but they
were not different in identifying sweet and salty stimuli. Taste detection thresholds via
electrogustometry were equivalent. Olfactory identification was significantly worse among
participants with autism. CONCLUSIONS: True differences exist in taste and olfactory
identification in autism. Impairment in taste identification with normal detection thresholds
suggests cortical, rather than brainstem dysfunction. Further research is needed to
determine the neurologic bases of olfactory and taste impairments, as well as the
relationship of chemosensory dysfunction to other characteristics of autism
538. Benoist G, Salomon LJ, Jacquemard F, Daffos F, Ville Y. The prognostic value of
ultrasound abnormalities and biological parameters in blood of fetuses infected with
cytomegalovirus. BJOG 2008;115(7):823-829.
Ref ID: 6329
Abstract: OBJECTIVE: To evaluate the prognostic value of ultrasound abnormalities and of
selected biological parameters in blood of fetuses infected with cytomegalovirus (CMV).
DESIGN: Retrospective observational study. SETTING: Two fetal medicine units in Paris,
France. POPULATION: All fetuses infected with CMV referred between 1998 and 2006.
METHODS: We retrospectively analysed data collected prospectively in 73 fetuses infected
by CMV with a positive CMV polymerase chain reaction in amniotic fluid. Fetal blood
sampling (FBS) was performed for evaluation of platelet count, plasma levels of
aminotransferases and gamma-glutamyl transpeptidases (GGT), presence of viraemia and
specific fetal immunoglobulin M. Targeted ultrasound examination was performed every
fortnight. Ultrasound findings were categorised into normal examination and any ultrasound
abnormality, which was further grouped as ultrasound abnormality of the fetal brain and
noncerebral ultrasound abnormality. MAIN OUTCOME MEASURES: A combination of
histological findings after termination of pregnancy and evidence of cytomegalic inclusion
disease at birth when pregnancies were continued. Clinical symptoms at birth or
histological lesions attributable to CMV were considered as poor outcome. Statistical
analysis was conducted to determine the value of each parameter to predict outcome.
Logistic regression was used to build up a multivariate model combining the relevant
parameters. RESULTS: In univariate analysis, only thrombocytopenia and the presence of
any ultrasound abnormality were associated with a poor outcome (P < 10(-4) for both
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abnormalities). In the multivariate analysis, both thrombocytopenia and the presence of
ultrasound abnormalities remained significant independent predictors of a poor outcome.
Based on univariate logistic regression, odds ratio for a poor outcome were 1.24, 7.2, 22.5
and 25.5 for each 10,000/mm(3) decrease in platelet count, the presence of noncerebral,
any ultrasound and cerebral ultrasound abnormalities, respectively. CONCLUSIONS: The
prognosis of CMV-infected fetuses relies independently on both targeted ultrasound
examination and fetal platelet count. FBS for platelet count may therefore justify FBS in
infected fetuses even in the absence of ultrasound. features of brain involvement
539. Benson DF, Geschwind N. Developmental Gerstmann syndrome. Neurology
1970;20(3):293-298.
Ref ID: 7464
540. Benton AL. Developmental aphasia and brain damage. Cortex 1964;1:40-52.
Ref ID: 924
541. Benton AL. Aphasia in children. Education 1959;79:408-412.
Ref ID: 923
542. Benvenuto A, Manzi B, Alessandrelli R, Galasso C, Curatolo P. Recent advances in the
pathogenesis of syndromic autisms. Int J Pediatr 2009;2009:198736.
Ref ID: 7099
Abstract: Background. Current advances in genetic technology continue to expand the list
of medical conditions associated with autism. Clinicians have to identify specific
autistic-related syndromes, and to provide tailored counseling. The aim of this study is to
elucidate recent advances in autism research that offer important clues into pathogenetic
mechanisms of syndromic autism and relevant implications for clinical practice. Data
Sources. The PubMed database was searched with the keywords "autism" and
"chromosomal abnormalities," "metabolic diseases," "susceptibility loci." Results. Defined
mutations, genetic syndromes, and metabolic diseases account for up to 20% of autistic
patients. Metabolic and mitochondrial defects may have toxic effects on the brain cells,
causing neuronal loss and altered modulation of neurotransmission systems. Alterations of
the neocortical excitatory/inhibitory balance and perturbations of interneurons' development
represent the most probable pathogenetic mechanisms underlying the autistic phenotype in
Fragile X-Syndrome and Tuberous Sclerosis Complex. Chromosomal abnormalities and
potential candidate genes are strongly implicated in the disruption of neural connections,
brain growth, and synaptic/dendritic morphology. Conclusion. Metabolic testing may be
appropriate if specific symptoms are present. High-resolution chromosome analysis may be
recommended if a specific diagnosis is suspected because of obvious dysmorphisms.
Identifying cryptic chromosomal abnormalities by whole genome microarray analysis can
increase the understanding of the neurobiological pathways to autism
543. Benvenuto A, Moavero R, Alessandrelli R, Manzi B, Curatolo P. Syndromic autism: causes
and pathogenetic pathways. World J Pediatr 2009;5(3):169-176.
Ref ID: 7100
Abstract: BACKGROUND: Autism is a severe neurodevelopmental disorder known to have
many different etiologies. In the last few years, significant progresses have been made in
comprehending the causes of autism and their multiple impacts on the developing brain.
This article aims to review the current understanding of the etiologies and the multiple
pathogenetic pathways that are likely to lead to the autistic phenotype. DATA SOURCES:
The PubMed database was searched with the keywords "autism" and "chromosomal
abnormalities", "metabolic diseases", "susceptibility loci". RESULTS: Genetic syndromes,
defined mutations, and metabolic diseases account for less than 20% of autistic patients.
Alterations of the neocortical excitatory/inhibitory balance and perturbations of interneurons'
development represent the most probable pathogenetic mechanisms underlying the autistic
phenotype in fragile X syndrome and tuberous sclerosis complex. Chromosomal
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abnormalities and potential candidate genes are strongly implicated in the disruption of
neural connections, brain growth and synaptic/dendritic morphology. Metabolic and
mitochondrial defects may have toxic effects on the brain cells, causing neuronal loss and
altered modulation of neurotransmission systems. CONCLUSIONS: A wide variety of
cytogenetic abnormalities have been recently described, particularly in the low functioning
individuals with dysmorphic features. Routine metabolic screening studies should be
performed in the presence of autistic regression or suggestive clinical findings. As
etiologies of autism are progressively discovered, the number of individuals with idiopathic
autism will progressively shrink. Studies of genetic and environmentally modulated
epigenetic factors are beginning to provide some clues to clarify the complexities of autism
pathogenesis. The role of the neuropediatrician will be to understand the neurological basis
of autism, and to identify more homogenous subgroups with specific biologic markers
544. Berchtold NC, Cribbs DH, Coleman PD et al. Gene expression changes in the course of
normal brain aging are sexually dimorphic. Proc Natl Acad Sci U S A
2008;105(40):15605-15610.
Ref ID: 5830
Abstract: Gene expression profiles were assessed in the hippocampus, entorhinal cortex,
superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact
individuals aged 20-99 years. Perspectives on global gene changes that are associated
with brain aging emerged, revealing two overarching concepts. First, different regions of the
forebrain exhibited substantially different gene profile changes with age. For example,
comparing equally powered groups, 5,029 probe sets were significantly altered with age in
the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change
occurred in the sixth to seventh decades across cortical regions, suggesting that this period
is a critical transition point in brain aging, particularly in males. Second, clear gender
differences in brain aging were evident, suggesting that the brain undergoes sexually
dimorphic changes in gene expression not only in development but also in later life.
Globally across all brain regions, males showed more gene change than females. Further,
Gene Ontology analysis revealed that different categories of genes were predominantly
affected in males vs. females. Notably, the male brain was characterized by global
decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily
enriched in energy production and protein synthesis/transport categories. Increased
immune activation was a prominent feature of aging in both sexes, with proportionally
greater activation in the female brain. These data open opportunities to explore
age-dependent changes in gene expression that set the balance between
neurodegeneration and compensatory mechanisms in the brain and suggest that this
balance is set differently in males and females, an intriguing idea
545. Berg AL, Spitzer JB, Towers HM, Bartosiewicz C, Diamond BE. Newborn hearing
screening in the NICU: profile of failed auditory brainstem response/passed otoacoustic
emission. Pediatrics 2005;116(4):933-938.
Ref ID: 6177
Abstract: OBJECTIVE: Incidence of a specific pattern of auditory responses, absent
auditory brainstem responses (ABRs) and present otoacoustic emissions (OAEs), in
newborn hearing screening in a regional perinatal center neonatal intensive care unit
(NICU) is described. This profile, labeled auditory neuropathy or auditory dyssynchrony
(AN/AD), is a dysfunction in neural/brainstem transmission that occurs in individuals whose
outer hairs cells are functioning normally. Although the AN/AD profile has been associated
with various risk factors, incidence and prediction are unknown. METHOD: Analysis of
electrophysiologic measures and medical record reviews of the first 22 months of the
universal newborn hearing-screening program was conducted. Association of the AN/AD
profile was evaluated with the following factors: gender, gestational age, ototoxic drug
regimen, low birth weight, hyperbilirubinemia, hydrocephalus, low Apgar score, anoxia,
respiratory distress syndrome, pulmonary hypertension, intraventricular hemorrhage,
multiple birth, seizure activity, and family history. RESULTS: One hundred fifteen (24.1%)
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of the 477 infants failed the ABR in 1 or both ears and passed OAEs bilaterally.
Comparisons of infants fitting the AN/AD profile with those not fitting the AN/AD profile were
negative with 3 exceptions: those with hyperbilirubinemia and those who were administered
vancomycin or furosemide. A logistic-regression analysis model failed to predict which
infants would be at risk for the AN/AD profile either unilaterally or bilaterally.
CONCLUSIONS: Screening of NICU infants should be conducted with ABR first, followed
by OAE after failure on ABR. Because the incidence of the AN/AD profile was found to be
24% in this at-risk population, additional study is warranted
546. Berg AT, Plioplys S, Tuchman R. Risk and Correlates of Autism Spectrum Disorder in
Children With Epilepsy: A Community-Based Study. J Child Neurol 2011.
Ref ID: 6950
Abstract: The prevalence of autism spectrum disorders for children with epilepsy in the
general population is unknown. In a prospective community-based study of newly
diagnosed childhood epilepsy, autism spectrum disorder was determined from parental
interviews, medical records, and expert reviews by a child psychiatrist. A total of 28 (5%)
participants had autism spectrum disorders. West syndrome (prevalence ratio = 4.53, P =
.002) and intellectual impairment (prevalence ratio = 4.34, P = .002) were independently
associated with autism spectrum disorder. Absent West syndrome, male gender was
associated with autism spectrum disorder (prevalence ratio = 3.71, P = .02). For
participants with overall normal cognitive abilities, 2.2% had autism spectrum disorder,
which is substantially higher than estimates from the general population (0.5%-0.9%). In
addition to West syndrome, which has repeatedly been shown to have a special
relationship with autism spectrum disorder, the most important determinants of autism
spectrum disorder in the general population (intellectual impairment and male sex) are also
important in young people with epilepsy
547. Berg JS, Brunetti-Pierri N, Peters SU et al. Speech delay and autism spectrum behaviors
are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome
region. Genet Med 2007;9(7):427-441.
Ref ID: 5177
Abstract: PURPOSE: Williams-Beuren syndrome is among the most well-characterized
microdeletion syndromes, caused by recurrent de novo microdeletions at 7q11.23 mediated
by nonallelic homologous recombination between low copy repeats flanking this critical
region. However, the clinical phenotype associated with reciprocal microduplication of this
genomic region is less well described. We investigated the molecular, clinical,
neurodevelopmental, and behavioral features of seven patients with dup(7)(q11.23),
including two children who inherited the microduplication from one of their parents, to more
fully characterize this emerging microduplication syndrome. METHODS: Patients were
identified by array-based comparative genomic hybridization. Clinical examinations were
performed on seven affected probands, and detailed cognitive and behavioral evaluations
were carried out on four of the affected probands. RESULTS: Our findings confirm initial
reports of speech delay seen in patients with dup(7)(q11.23) and further delineate and
expand the phenotypic spectrum of this condition to include communication, social
interactions, and repetitive interests that are often observed in individuals diagnosed with
autism spectrum disorders. CONCLUSIONS: Array-based comparative genomic
hybridization is a powerful means of detecting genomic imbalances and identifying
molecular etiologies in the clinic setting, including genomic disorders such as
Williams-Beuren syndrome and dup(7)(q11.23). We propose that dup(7)(q11.23) syndrome
may be as frequent as Williams-Beuren syndrome and a previously unrecognized cause of
language delay and behavioral abnormalities. Indeed, these individuals may first be
referred for evaluation of autism, even if they do not ultimately meet diagnostic criteria for
an autism spectrum disorder
548. Berger M, Yule W, Rutter M. Attainment and adjustment in two geographical areas. II--The
prevalence of specific reading retardation. Br J Psychiatry 1975;126:510-519.
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Ref ID: 77
Abstract: Specific reading retardation was found to occur in a minimum of 9-9 per cent of
ten-year-old 'indigenous' children in one inner London borough. This rate was nearly three
times that (3-9 per cent) in Isle of Wight children. There was a comparably higher rate of
general reading backwardness in London (19-0 per cent vs 8-3 per cent). Since the same
epidemiological methods were followed in the two areas, and since the reading-retarded
children had similar psychological characteristics in both cases, it is concluded that there is
a real difference between London and the Isle of Wight in the prevalence of reading
retardation and of reading backwardness
549. Berges J, Lezine I. The Imitation of Gestures. London, U.K.: Heinemann; 1965.
Ref ID: 1400
550. Bergman K, Glover V, Sarkar P, Abbott DH, O'Connor TG. In utero cortisol and
testosterone exposure and fear reactivity in infancy. Horm Behav 2010;57(3):306-312.
Ref ID: 6748
Abstract: Fetal programming is emerging as a major conceptual model for understanding
developmental origins of health and disease, including behavioral outcomes. As part of a
larger study of prenatal stress and child development, we examined the association
between prenatal hormone exposure and fear reactivity, a temperament dimension that is a
predictor of long-term behavioral adjustment. Amniotic fluid was collected from a sample of
women undergoing clinically indicated amniocentesis for later analysis of cortisol and
testosterone. Children with normal birth outcomes were recalled for follow-up assessment
at 17 months, at which time we administered an observational assessment of temperament
(lab-TAB; n=108). Information on pregnancy and obstetric outcome was included as
covariates. Results indicated that there was a significant association between prenatal
testosterone and observed fear reactivity in boys (r(53)=0.34, p=0.01); no significant effect
was found in girls (r(54)=-0.07, ns); the effect remained when obstetric, psychosocial, and
parental anxiety were controlled for. There was not a significant association between fetal
cortisol exposure and fear reactivity. The prediction from in utero testosterone exposure to
fear reactivity in boys extends prior research on prenatal testosterone and may represent
an association with a general predisposition to greater arousal and reactivity
551. Bergmann TO, Molle M, Diedrichs J, Born J, Siebner HR. Sleep spindle-related reactivation
of category-specific cortical regions after learning face-scene associations. Neuroimage
2012;59(3):2733-2742.
Ref ID: 7540
Abstract: Newly acquired declarative memory traces are believed to be reactivated during
NonREM sleep to promote their hippocampo-neocortical transfer for long-term storage. Yet
it remains a major challenge to unravel the underlying neuronal mechanisms. Using
simultaneous electroencephalography (EEG) and functional magnetic resonance imaging
(fMRI) recordings in humans, we show that sleep spindles play a key role in the reactivation
of memory-related neocortical representations. On separate days, participants either
learned face-scene associations or performed a visuomotor control task. Spindle-coupled
reactivation of brain regions representing the specific task stimuli was traced during
subsequent NonREM sleep with EEG-informed fMRI. Relative to the control task, learning
face-scene associations triggered a stronger combined activation of neocortical and
hippocampal regions during subsequent sleep. Notably, reactivation did not only occur in
temporal synchrony with spindle events but was tuned by ongoing variations in spindle
amplitude. These learning-related increases in spindle-coupled neocortical activity were
topographically specific because reactivation was restricted to the face- and
scene-selective visual cortical areas previously activated during pre-sleep learning.
Spindle-coupled hippocampal activation was stronger the better the participant had
performed at prior learning. These results are in agreement with the notion that sleep
spindles orchestrate the reactivation of new hippocampal-neocortical memories during
sleep
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552. Bergstrom L, Baker BB. Syndromes associated with congenital facial paralysis. Otolaryngol
Head Neck Surg 1981;89(2):336-342.
Ref ID: 6369
Abstract: Thirty-five of 1,488 pediatric otologic cases had congenital facial nerve weakness.
A cause was generally not found, but two probably had nuclear dysgenesis; one may have
had an intracanalicular lesion; two cases resulted from teratogens, one from poor
intrauterine environment, and three from genetic complications. Five had total unilateral
paralysis; one had bilateral palsy. Frequent associated anomalies were microtiaatresia,
hemifacial microsomia, facial clefts, Moebius syndrome, and congenital conductive
sensorineural loss
553. Berk RA. Screening and Diagnosis of Children with Learning Disabilities. Springfield, IL:
Charles C. Thomas; 1984.
Ref ID: 925
554. Berkson G. Early development of stereotyped and self-injurious behaviors: II. Age trends.
Am J Ment Retard 2002;107(6):468-477.
Ref ID: 4926
Abstract: Thirty-nine infants who were served in early intervention programs and who
engaged in stereotyped or self-injurious behaviors were studied weekly from the time they
entered the school until they were 3 years old. The development of these behaviors
increased and declined over age more slowly than in typical babies. A few children retained
the behaviors for long periods, and some were still showing them when they left the
program. The hypothesis that body-rocking promotes motor development was not
supported. Indeed, body-rocking may be a consequence of motor development.
Head-banging seemed to be related to tantrums, whereas eye-poking developed early and
seemed to be self-stimulatory. Suggestions for early treatment are presented
555. Berkson G, Tupa M, Sherman L. Early development of stereotyped and self-injurious
behaviors: I. Incidence. Am J Ment Retard 2001;106(6):539-547.
Ref ID: 4927
Abstract: From five programs with 457 eligible children, 39 children younger than 40
months who had developmental disabilities were studied. Video sampling, observation
notes, parent reports, staff reports, and clinical records were the data sources. Twenty-one
children, or 4.6% of the total number in the program, exhibited SIBs. Virtually all children in
the sample who were motorically capable of it showed body-rocking in at least one position.
The SIBs were directed mainly toward the head, and body-rocking occurred mainly in
four-point and seated position
556. Berkson G, Andriacchi T, Sherman L. More information on the nature of stereotyped
body-rocking. Am J Ment Retard 2001;106(3):205-208.
Ref ID: 4928
Abstract: Body-rocking was exposed to kinematic analysis in two studies. In the first study,
amplitude was larger in the natural body-rocking of individuals with mental retardation than
in the natural body-rocking of college students. Variability did not differ. In the second
study, natural body-rocking of people with mental retardation was compared with their
artificial body-rocking. Amplitude and variability were larger in the artificial condition.
However, this result was not clear. We suggest that group and condition differences might
have been a function of practice
557. Berkson G, Rafaeli-Mor N, Tarnovsky S. Body-rocking and other habits of college students
and persons with mental retardation. Am J Ment Retard 1999;104(2):107-116.
Ref ID: 4930
Abstract: Prevalence of body-rocking in college students was assessed, and the
characteristics of body-rocking of college students were compared to those of individuals
with mental retardation. For college students, the prevalence depended on the
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restrictiveness of the method used and varied between 3% and 25%. Video samples
showed that when compared with college students, a greater proportion of people with
mental retardation engage in body-rocking, seem less sensitive to situational factors,
demonstrate atypical collateral behaviors, engage in less leg-kicking, and execute their
body-rocking with larger amplitudes. There were no differences in duration or number of
individual rocks or bouts of body-rocking. We conclude that body-rocking is a "normal"
behavior whose form of expression may become atypical
558. Berkson G, Gutermuth L, Baranek G. Relative prevalence and relations among stereotyped
and similar behaviors. Am J Ment Retard 1995;100(2):137-145.
Ref ID: 4931
Abstract: Relative prevalence and relations among stereotyped and similar behaviors were
studied in 246 children and adults with developmental disabilities. For each subject, two
staff members who knew the participant at least moderately well filled out a checklist of 54
items that sampled various forms of stereotyped behaviors, abnormal focused affections,
compulsions, rigidity, savant skills, and defensiveness. Agreements between raters for
individual participants were low to moderate. However, the item prevalence scores for the
two groups of observers were stable. Correlations between several items were significant.
Factor analyses produced weak evidence for a general Stereotypy factor and further
evidence for 6 to 8 subfactors, some of which are generally consistent with accepted
classification of the types of behaviors studied here
559. Berkson G. Repetitive stereotyped behaviors. Am J Ment Def 1983;88(3):239-246.
Ref ID: 2399
Abstract: This paper points to factors that determine whether repetitive stereotyped
behavior occur in the behavior repertoire. The analysis pits an "intrinsic oscillator"
mechanism against a "self-stimulation" theory and chooses to emphasize the latter. The
paper accounts for the repetitive and rhythmic nature of stereotypy by suggesting that
repetition in a rhythmic way is the most efficient way of self-stimulation. It proposes that
rhythm may be a reinforcement in at least some cases. It raises the question of whether
control of stimulation by the person is a necessary condition for maintaining stereotypy. The
paper recognizes the possibility that stereotyped behaviors may have their origin in the
common repetitive behaviors of infancy but emphasizes that pathological stereotypy may
involve more than immature repetition. It suggests that there is reason to believe that early
intervention to prevent pathological stereotyped behavior might be effective but that we do
not know much about how stereotypies get started
560. Berl MM, Mayo J, Parks EN et al. Regional differences in the developmental trajectory of
lateralization of the language network. Hum Brain Mapp 2012.
Ref ID: 7742
Abstract: The timing and developmental factors underlying the establishment of language
dominance are poorly understood. We investigated the degree of lateralization of traditional
frontotemporal and modulatory prefrontal-cerebellar regions of the distributed language
network in children (n = 57) ages 4 to 12-a critical period for language consolidation. We
examined the relationship between the strength of language lateralization and
neuropsychological measures and task performance. The fundamental language network is
established by four with ongoing maturation of language functions as evidenced by
strengthening of lateralization in the traditional frontotemporal language regions; temporal
regions were strongly and consistently lateralized by age seven, while frontal regions had
greater variability and were less strongly lateralized through age 10. In contrast, the
modulatory prefrontal-cerebellar regions were the least strongly lateralized and degree of
lateralization was not associated with age. Stronger core language skills were significantly
correlated with greater right lateralization in the cerebellum. Hum Brain Mapp, 2012. (c)
2012 Wiley Periodicals, Inc
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561. Berlin CI, Hood L, Morlet T, Rose K, Brashears S. Auditory neuropathy/dys-synchrony:
diagnosis and management. MRDDRR 2003;9(4):225-231.
Ref ID: 6454
Abstract: Auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs) are
objective measures of auditory function, but are not hearing tests. Normal OAEs reflect
normal cochlear outer hair cell function, and an ABR indicates a synchronous neural
response. It is quite possible for a patient to have normal OAEs but absent or grossly
abnormal ABR and a behavioral audiogram that is inconsistent with either test. These
patients, who may constitute as much as 10% of the diagnosed deaf population, have
auditory neuropathy/dys-synchrony (AN/AD). To diagnose AN/AD accurately, ABRs are
obtained in response to condensation and rarefaction clicks to distinguish cochlear
microphonics (CM) from neural responses. Appropriate management is confounded by
variation among patients and changes in auditory function in some patients over time.
Recommendations for management include visual language exposure through methods
such as American Sign Language (ASL), Cued Speech, or baby signs, and closely
following patients
562. Berlin CI, Morlet T, Hood LJ. Auditory neuropathy/dyssynchrony: its diagnosis and
management. Pediatr Clin North Am 2003;50(2):331-viii.
Ref ID: 6455
Abstract: Patients with auditory neuropathy/dyssynchrony exhibit no auditory brain stem
response (ABR), no middle ear muscle response, and both normal otoacoustic emissions
or normal cochlear microphonics. An absent or grossly abnormal ABR is not always
associated with deafness. In contrast, a hearing loss of 30 dB or more usually predicts
absent otoacoustic emissions, but normal emissions can be seen in some patients whose
behavioral audiograms imply total deafness. This article reviews the underlying physiology
that makes these tests both useful and potentially misleading, and recommends steps to be
considered by primary care physicians and other professionals to compensate for the
vulnerabilities of each of the procedures
563. Berlin CI, Hood LJ, Hurley A, Wen H. The First Jerger Lecture. Contralateral suppression of
otoacoustic emissions: an index of the function of the medial olivocochlear system.
Otolaryngol Head Neck Surg 1994;110(1):3-21.
Ref ID: 4042
Abstract: We can now distinguish, in part, between nerve deafness and hair cell deafness
through the use of otoacoustic emissions. We can also assess the efferent system by
carefully quantifying the effects of contralateral stimulation on these same otoacoustic
emissions. The suppression of transient evoked emissions by continuous contralateral
white noise is an ostensibly small effect of 2 or 3 dB when studied over a 20-msec window.
However, when subjected to microstructural analysis, the effect can exceed 6 to 8 dB in the
zones from 10 to 20 msec after the stimulus has subsided. Temporal and spectral analyses
reveal robust effects of contralateral lateral stimulation, although in any given normal
subject it may be difficult to separate middle ear effects from efferent effects. Evidence is
strong that the efferent effect is mediated in part by cholinergic-primarily nicotinic-receptors
in the outer hair cell. However, a unique type of patient, who shows nearly normal
pure-tone audiograms and absent ABRs, shows virtually no contralateral suppression of
transient evoked emissions. Some other patients, with symptoms of Charcot-Marie-Tooth
disease, may paradoxically show extremely poor audiograms, but perfectly normal evoked
emissions along with absent contralateral suppression. The ABR, along with middle ear
muscle reflexes and masking level differences, are all absent in these patients; we
therefore think they have a disorder that desynchronizes most of their primary auditory
nerve fibers and thereby disconnects them from any efferent activity or masking
cancellation. The existence of such an auditory disorder, characterized by severe
dysfunction in speech comprehension-especially when listening in noise-suggests that what
appears to be a "central auditory imperception" might stem instead from a systemic
peripheral primary neuropathy
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564. Bernabei P, Cerquiglini A, Cortesi F, D'Ardia C. Regression Versus No Regression in the
Autistic Disorder: Developmental Trajectories. J Autism Dev Disord 2006.
Ref ID: 4943
Abstract: Developmental regression is a complex phenomenon which occurs in 20-49% of
the autistic population. Aim of the study was to assess possible differences in the
development of regressed and non-regressed autistic preschoolers. We longitudinally
studied 40 autistic children (18 regressed, 22 non-regressed) aged 2-6 years. The following
developmental areas were considered fundamental in the first years of life, and were
assessed at ages 2, 3, 4, 5, and 6: receptive and expressive language, communicative and
request modalities, play activities, and mental age. Children who regressed showed lower
mean performances than those who did not regress and, in the time intervals considered,
non-regressed children improved their ratings in the above mentioned variables
significantly more than regressed children
565. Bernal J. Action of thyroid hormone in brain. J Endocrinol Invest 2002;25(3):268-288.
Ref ID: 6253
Abstract: Among the most critical actions of thyroid hormone in man and other mammals
are those exerted on brain development. Severe hypothyroidism during the neonatal period
leads to structural alterations, including hypomyelination and defects of cell migration and
differentiation, with long-lasting, irreversible effects on behavior and performance. A
complex regulatory mechanism operates in brain involving regulation of the concentration
of the active hormone, T3, and the control of gene expression. Most brain T3 is formed
locally from its precursor, T4, by the action of type II deiodinase which is expressed in glial
cells, tanycytes, and astrocytes. Type III deiodinase (DIII) is also involved in the regulation
of T3 concentrations, especially during the embryonic and early post-natal periods. DIII is
expressed in neurons and degrades T4 and T3 to inactive metabolites. The action of T3 is
mediated through nuclear receptors, which are expressed mainly in neurons. The receptors
are ligand-modulated transcription factors, and a number of genes have been identified as
regulated by thyroid hormone in brain. The regulated genes encode proteins of myelin,
mitochondria, neurotrophins and their receptors, cytoskeleton, transcription factors, splicing
regulators, cell matrix proteins, adhesion molecules, and proteins involved in intracellular
signaling pathways. The role of thyroid hormone is to accelerate changes of gene
expression that take place during development. Surprisingly, null-mutant mice for the T3
receptors show almost no signs of central nervous system involvement, in contrast with the
severe effects of hypothyroidism. The resolution of this paradox is essential to understand
the role of thyroid hormone and its receptors in brain development and function
566. Bernard S, Enayati A, Roger H, Binstock T, Redwood L. The role of mercury in the
pathogenesis of autism. Mol Psychiatry 2002;7 Suppl 2:S42-S43.
Ref ID: 3690
567. Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of mercury
poisoning. Med Hypotheses 2001;56(4):462-471.
Ref ID: 3660
Abstract: Autism is a syndrome characterized by impairments in social relatedness and
communication, repetitive behaviors, abnormal movements, and sensory dysfunction.
Recent epidemiological studies suggest that autism may affect 1 in 150 US children.
Exposure to mercury can cause immune, sensory, neurological, motor, and behavioral
dysfunctions similar to traits defining or associated with autism, and the similarities extend
to neuroanatomy, neurotransmitters, and biochemistry. Thimerosal, a preservative added to
many vaccines, has become a major source of mercury in children who, within their first
two years, may have received a quantity of mercury that exceeds safety guidelines. A
review of medical literature and US government data suggests that: (i) many cases of
idiopathic autism are induced by early mercury exposure from thimerosal; (ii) this type of
autism represents an unrecognized mercurial syndrome; and (iii) genetic and non-genetic
138
factors establish a predisposition whereby thimerosal's adverse effects occur only in some
children
568. Bernardes de Jesus BM, Bjoras M, Coin F, Egly JM. Dissection of the molecular defects
caused by pathogenic mutations in the DNA repair factor XPC. Mol Cell Biol
2008;28(23):7225-7235.
Ref ID: 6067
Abstract: XPC is responsible for DNA damage sensing in nucleotide excision repair (NER).
Mutations in XPC lead to a defect in NER and to xeroderma pigmentosum (XP-C). Here,
we analyzed the biochemical properties behind mutations found within three patients: one
amino acid substitution (P334H, XP1MI, and GM02096), one amino acid incorporation in a
conserved domain (697insVal, XP8BE, and GM02249), and a stop mutation (R579St,
XP67TMA, and GM14867). Using these mutants, we demonstrated that HR23B stabilizes
XPC on DNA and protects it from degradation. XPC recruits the transcription/repair factor
TFIIH and stimulates its XPB ATPase activity to initiate damaged DNA opening. In an effort
to understand the severity of XP-C phenotypes, we also demonstrated that single
mutations in XPC perturb other repair processes, such as base excision repair (e.g., the
P334H mutation prevents the stimulation of Ogg1 glycosylase because it thwarts the
interaction between XPC and Ogg1), thereby leading to a deeper understanding of the
molecular repair defect of the XP-C patients
569. Bernardini GL, Herrera DG, Carson D et al. Adult-onset Krabbe's disease in siblings with
novel mutations in the galactocerebrosidase gene. Ann Neurol 1997;41(1):111-114.
Ref ID: 2268
Abstract: Krabbe's disease or globoid cell leukodystrophy is a rare demyelinating disorder
of the central and peripheral nervous systems, the diagnosis of which is based on clinical
findings and the determination of low to absent functional activity of the enzyme
beta-galactocerebrosidase. We report the presentation of late-onset Krabbe's disease in 2
siblings, a 17-year-old boy and his 16-year-old sister, both with marked deficiency of the
enzyme beta-galactocerebrosidase. Only the older sibling manifested clinical signs and
symptoms of the disease, while the younger sister remained asymptomatic to date.
Molecular analyses disclosed the presence in this family of two novel single point mutations
within the gene for galactocerebrosidase
570. Bernardo AB. Language and mathematical problem solving among bilinguals. J Psychol
2002;136(3):283-297.
Ref ID: 7518
Abstract: Does using a bilingual's 1st or 2nd language have an effect on problem solving in
semantically rich domains like school mathematics? The author conducted a study to
determine whether Filipino-English bilingual students' understanding and solving of word
problems in arithmetic differed when the problems were in the students' 1st and 2nd
languages. Two groups participated-students whose 1st language was Filipino and
students whose 1st language was English-and easy and difficult arithmetic problems were
used. The author used a recall paradigm to assess how students understood the word
problems and coded the solution accuracy to assess problem solving. The results indicated
a 1st-language advantage; that is, the students were better able to understand and solve
problems in their 1st language, whether the 1st language was English or Filipino. Moreover,
the advantage was more marked with the easy problems. The theoretical and practical
implications of the results are discussed
571. Berney TP, Ireland M, Burn J. Behavioural phenotype of Cornelia de Lange syndrome.
Arch Dis Child 1999;81(4):333-336.
Ref ID: 3260
Abstract: A postal questionnaire was used to study 49 individuals with Cornelia de Lange
syndrome (including both the classical and the mild forms) to ascertain behavioural
phenotype. Ages ranged from early childhood to adulthood (mean age, 10.2 years; SD, 7.8)
139
and the degree of mental retardation from borderline (10%), through mild (8%), moderate
(18%), and severe (20%) to profound (43%). A wide variety of symptoms occurred
frequently, notably hyperactivity (40%), self injury (44%), daily aggression (49%), and sleep
disturbance (55%). These correlated closely with the presence of an autistic like syndrome
and with the degree of mental retardation. The frequency and severity of disturbance,
continuing beyond childhood, is important when planning the amount and duration of
support required by parents
572. Berney TP, Ireland M, Burn J. Behavioural phenotype of Cornelia de Lange syndrome.
Arch Dis Child 1999;81(4):333-336.
Ref ID: 3271
Abstract: A postal questionnaire was used to study 49 individuals with Cornelia de Lange
syndrome (including both the classical and the mild forms) to ascertain behavioural
phenotype. Ages ranged from early childhood to adulthood (mean age, 10.2 years; SD, 7.8)
and the degree of mental retardation from borderline (10%), through mild (8%), moderate
(18%), and severe (20%) to profound (43%). A wide variety of symptoms occurred
frequently, notably hyperactivity (40%), self injury (44%), daily aggression (49%), and sleep
disturbance (55%). These correlated closely with the presence of an autistic like syndrome
and with the degree of mental retardation. The frequency and severity of disturbance,
continuing beyond childhood, is important when planning the amount and duration of
support required by parents
573. Berninger VW, Abbott RD, Augsburger A, Garcia N. Comparison of pen and keyboard
transcription modes in children with and without learning disabilities. Learning Disability
Quarterly 2009;32:123-141.
Ref ID: 7373
Abstract: Abstract. Fourth graders with learning disabilities in transcription
(handwriting and spelling), LD-TD, and without LD-TD (nonLD), were compared on three writing tasks (letters, sentences, and
essays), which differed by level of language, when writing by pen
and by keyboard. The two groups did not differ significantly
in Verbal IQ but did in handwriting, spelling, and composing
achievement. Although LD-TD and non-LD groups did not differ
in total time for producing letters by pen or keyboard, both groups
took longer to compose sentences and essays by keyboard than by
pen. Students in both groups tended to show the same pattern of
results for amount written as a larger sample of typically developing
fourth graders who composed longer essays by pen. Results for
that sample, which also included typically developing second and
sixth graders, showed that effects of transcription mode vary with
level of language and within level of language by grade level for
letters and sentences. However, consistently from second to fourth
to sixth grade, children wrote longer essays with faster word production
rate by pen than by keyboard. In addition, fourth and
sixth graders wrote more complete sentences when writing by pen
than by keyboard, and this relative advantage for sentence composing
in text was not affected by spelling ability. Implications of
the results for using computers for accommodations or specialized
instruction for students with LD-TD are discussed.
574. Berry-Kravis E, Abrams L, Coffey SM et al. Fragile X-associated tremor/ataxia syndrome:
clinical features, genetics, and testing guidelines. Mov Disord 2007;22(14):2018-30, quiz.
Ref ID: 6012
Abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative
disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated
findings include parkinsonism, executive function deficits and dementia, neuropathy, and
140
dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2
signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients.
Similar signal alterations are seen in deep and subependymal cerebral white matter, as is
general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is
the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution
throughout the brain and brainstem. FXTAS is caused by moderate expansions (55-200
repeats; premutation range) of a CGG trinucleotide in the fragile X mental retardation 1
(FMR1) gene, the same gene which causes fragile X syndrome when in the full mutation
range (200 or greater CGG repeats). The pathogenic mechanism is related to
overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered,
and hence currently under-diagnosed, FXTAS is likely to be one of the most common
single-gene disorders leading to neurodegeneration in males. In this report, we review
information available on the clinical, radiological, and pathological features, and prevalence
and management of FXTAS. We also provide guidelines for the practitioner to assist with
identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for
genetic counseling once a diagnosis of FXTAS is made
575. Berry CL, Vogler C, Galvin NJ, Birkenmeier EH, Sly WS. Pathology of the ear in murine
mucopolysaccharidosis type VII. Morphologic correlates of hearing loss. Lab Invest
1994;71(3):438-445.
Ref ID: 6360
Abstract: BACKGROUND: Patients with mucopolysaccharidosis commonly have hearing
impairment but the morphologic alterations in the ear caused by these lysosomal storage
diseases are incompletely defined. EXPERIMENTAL DESIGN: We studied a murine model
of mucopolysaccharidosis VII with clinical features, including conductive hearing loss and
biochemical, and pathologic features similar to those seen in human
mucopolysaccharidoses. Gross morphology, radiography, light and electron microscopy
were used to define the pathologic alterations in the ear that correlate with auditory
dysfunction in mucopolysaccharidosis VII. RESULTS: Cerumen occluded the external
auditory canal and there was a severe otitis media. The bone encasing the middle and
inner ear was sclerotic and opaque and the temporal bone and the ossicles and their joints
contained cells distended by enlarged lysosomes. Hair cell damage and multifocal
lysosomal distention in endoneural fibroblasts and spiral ganglion neurons characterized
the mucopolysaccharidosis VII cochlea. CONCLUSIONS: The external auditory canal
obstruction, otitis media, and ossicle articular alterations in mucopolysaccharidosis VII mice
cause a conductive hearing loss. The hair cell damage and neuronal storage may
contribute to sensorineural deafness. This model allows investigation of the
pathophysiology of auditory dysfunction in mucopolysaccharidosis and the effects of
therapies on hearing loss
576. Berthier ML, Kulisevsky J, Asenjo B, Aparicio J, Lara D. Comorbid Asperger and Tourette
syndromes with localized mesencephalic, infrathalamic, thalamic, and striatal damage. Dev
Med Child Neurol 2003;45(3):207-212.
Ref ID: 4642
Abstract: We describe the coexistence of Asperger and Tourette syndromes (AS and TS)
caused by discrete hypoxic-ischaemic necrosis of the midbrain, infrathalamic and thalamic
nuclei, and striatum in an adolescent male with positive family history for tics and
obsessive-compulsive disorder. Behavioural ratings, cognitive tests, and volumetric
measurements of the basal ganglia were performed in the patient and five other individuals
with AS-TS unassociated with MRI lesions. Cognitive deficits in attentional, executive, and
visual-spatial domains were found both in the patient and control AS-TS group, though
deficits were more severe in the former. MRI showed reduction of the left basal ganglia
volume compared with the right in the patient, whereas the control group showed reduction
of right basal ganglia volume compared with the left. It is suggested that individuals with a
genetic predisposition to TS may develop AS and TS after involvement of midbrain and
141
related components of basal ganglia-thalamocortical circuits normally implicated in the
integration of emotional, cognitive, and motor functions
577. Bertolini P, Lassalle M, Mercier G et al. Platinum compound-related ototoxicity in children:
long-term follow-up reveals continuous worsening of hearing loss
2. J Pediatr Hematol Oncol 2004;26(10):649-655.
Ref ID: 6310
Abstract: OBJECTIVES: The purpose of this study was to evaluate the severity of hearing
loss after cisplatin and/or carboplatin treatment in young children and to analyze its
evolution and its relation to different therapy schedules. METHODS: One hundred twenty
patients treated in the Pediatrics Department at the Institut Gustave-Roussy from 1987 to
1997 for neuroblastoma, osteosarcoma, hepatoblastoma, or germ cell tumors were
analyzed. Median age at diagnosis was 2.6 (range 0-17) years. Median follow-up was 7
(1-13) years. Chemotherapy regimens contained cisplatin and/or carboplatin. Three
patients also received high-dose carboplatin. Cisplatin was administered at a dose of 200
mg/m/course in 72% of cases. The median cumulative dose was 400 mg/m for cisplatin
and 1,600 mg/m for carboplatin. Hearing loss of grade 2 or above, according to Brock's
grading scale, was revealed with pure tone audiometry and behavioral techniques.
RESULTS: Carboplatin alone was not ototoxic. Deterioration of hearing of grade 2 or above
was observed in 37% of patients treated with cisplatin and 43% of patients treated with
cisplatin plus carboplatin (P = NS). Fifteen percent of patients experienced grade 3 or 4
ototoxicity. Ototoxicity was most often observed after a total cisplatin dose of at least 400
mg/m. No improvement was observed with time; on the contrary, worsening or progression
of hearing loss at lower frequencies was detected during follow-up. Only 5% of audiograms
showed toxicity of at least grade 2 before the end of therapy; in contrast, this level was
observed in 11% of early post-therapy evaluations and in 44% after more than 2 years of
follow-up. CONCLUSIONS: Children treated with cisplatin at cumulative doses approaching
400 mg/m require long-term surveillance to avoid overlooking hearing deficits. Carboplatin,
at a standard dose, does not appear to be a significant risk factor for ototoxicity even in
patients who have already been treated with cisplatin
578. Bertoncini J, Morais J, Bijeljac-Babic R, McAdams S, Peretz I, Mehler J. Dichotic
perception and laterality in neonates. Brain Lang 1989;37:591-605.
Ref ID: 715
579. Bertone A, Mottron L, Jelenic P, Faubert J. Enhanced and diminished visuo-spatial
information processing in autism depends on stimulus complexity. Brain 2005;128(Pt
10):2430-2441.
Ref ID: 4674
Abstract: Visuo-perceptual processing in autism is characterized by intact or enhanced
performance on static spatial tasks and inferior performance on dynamic tasks, suggesting
a deficit of dorsal visual stream processing in autism. However, previous findings by
Bertone et al. indicate that neuro-integrative mechanisms used to detect complex motion,
rather than motion perception per se, may be impaired in autism. We present here the first
demonstration of concurrent enhanced and decreased performance in autism on the same
visuo-spatial static task, wherein the only factor dichotomizing performance was the neural
complexity required to discriminate grating orientation. The ability of persons with autism
was found to be superior for identifying the orientation of simple, luminance-defined (or
first-order) gratings but inferior for complex, texture-defined (or second-order) gratings.
Using a flicker contrast sensitivity task, we demonstrated that this finding is probably not
due to abnormal information processing at a sub-cortical level (magnocellular and
parvocellular functioning). Together, these findings are interpreted as a clear indication of
altered low-level perceptual information processing in autism, and confirm that the deficits
and assets observed in autistic visual perception are contingent on the complexity of the
neural network required to process a given type of visual stimulus. We suggest that atypical
142
neural connectivity, resulting in enhanced lateral inhibition, may account for both enhanced
and decreased low-level information processing in autism
580. Bertone A, Mottron L, Jelenic P, Faubert J. Motion perception in autism: a "complex" issue.
J Cogn Neurosci 2003;15(2):218-225.
Ref ID: 4744
Abstract: We present the first assessment of motion sensitivity for persons with autism and
normal intelligence using motion patterns that require neural processing mechanisms of
varying complexity. Compared to matched controls, our results demonstrate that the motion
sensitivity of observers with autism is similar to that of nonautistic observers for different
types of first-order (luminance-defined) motion stimuli, but significantly decreased for the
same types of second-order (texture-defined) stimuli. The latter class of motion stimuli has
been demonstrated to require additional neural computation to be processed adequately.
This finding may reflect less efficient integrative functioning of the neural mechanisms that
mediate visuoperceptual processing in autism. The contribution of this finding with regards
to abnormal perceptual integration in autism, its effect on cognitive operations, and possible
behavioral implications are discussed
581. Bertrand J, Mars A, Boyle C, Bove F, Yeargin-Allsopp M. Prevalence of autism in a United
States population: Brick Township, NJ. Paediatr Perinat Epidemiol 2001;15(4):A4.
Ref ID: 3467
582. Bertrand J, Mars A, Boyle C, Bove F, Yeargin-Allsopp M, Decoufle P. Prevalence of autism
in a United States population: the Brick Township, New Jersey, investigation. Pediatrics
2001;108(5):1155-1161.
Ref ID: 3822
Abstract: OBJECTIVE: This study determined the prevalence of autism for a defined
community, Brick Township, New Jersey, using current diagnostic and epidemiologic
methods. METHODS: The target population was children who were 3 to 10 years of age in
1998, who were residents of Brick Township at any point during that year, and who had an
autism spectrum disorder. Autism spectrum disorder was defined as autistic disorder,
pervasive developmental disorder-not otherwise specified (PDD-NOS), and Asperger
disorder. The study used 4 sources for active case finding: special education records,
records from local clinicians providing diagnosis or treatment for developmental or
behavioral disabilities, lists of children from community parent groups, and families who
volunteered for participation in the study in response to media attention. The autism
diagnosis was verified (or ruled out) for 71% of the children through clinical assessment.
The assessment included medical and developmental history, physical and neurologic
evaluation, assessment of intellectual and behavioral functioning, and administration of the
Autism Diagnostic Observation Schedule-Generic. RESULTS: The prevalence of all autism
spectrum disorders combined was 6.7 cases per 1000 children. The prevalence for children
whose condition met full diagnostic criteria for autistic disorder was 4.0 cases per 1000
children, and the prevalence for PDD-NOS and Asperger disorder was 2.7 cases per 1000
children. Characteristics of children with autism in this study were similar to those in
previous studies of autism. CONCLUSIONS: The prevalence of autism in Brick Township
seems to be higher than that in other studies, particularly studies conducted in the United
States, but within the range of a few recent studies in smaller populations that used more
thorough case-finding methods
583. Berument SK, Starr E, Pickles A et al. Pre-Linguistic Autism Diagnostic observation
Schedule adapter for oleder individuals with severe to profound mental retardation: a pilot
study. J Autism Dev Disord 2005;35(6):821-829.
Ref ID: 4651
584. Berument SK, Rutter M, Lord C, Pickles A, Bailey A. Autism screening questionnaire:
diagnostic validity. Br J Psychiatry 1999;175(444):451.
143
Ref ID: 3280
Abstract: BACKGROUND: Good interview and diagnostic measures for autism and other
pervasive developmental disorders (PDDs) are available but there is a lack of a good
screening questionnaire. AIMS: To develop and test a screening questionnaire based on
items in the best available diagnostic interview--the Autism Diagnostic Interview--Revised
(ADI-R). METHOD: A 40-item scale, the Autism Screening Questionnaire (ASQ), was
developed and tested on a sample of 160 individuals with PDD and 40 with non-PDD
diagnoses. RESULTS: The ASQ has good discriminative validity with respect to the
separation of PDD from non-PDD diagnoses at all IQ levels, with a cut-off of 15 proving
most effective. The differentiation between autism and other varieties of PDD was weaker.
CONCLUSIONS: The ASQ is an effective screening questionnaire for PDD
585. Besag FM. Cognitive and behavioral outcomes of epileptic syndromes: implications for
education and clinical practice. Epilepsia 2006;47 Suppl 2:119-125.
Ref ID: 6841
Abstract: The educational and social progress of a child with epilepsy depends not only on
seizure control but also on cognitive and behavioral factors. The various epilepsy
syndromes of childhood and adolescence differ greatly in terms of cognitive and behavioral
outcome. A high proportion of babies who have West syndrome and children who have
Dravet syndrome (severe myoclonic epilepsy in infancy) will have long-term cognitive and
behavioral problems. The Lennox-Gastaut syndrome also often has a poor prognosis in this
regard. Children with the Landau-Kleffner syndrome have a variable prognosis, some
regain speech and others have permanent speech impairment. Benign childhood epilepsy
with centrotemporal spikes is now recognised as lying on a spectrum with the
Landau-Kleffner syndrome: mild cases have few if any cognitive or behavioral problems but
others may have quite severe difficulties. People with juvenile myoclonic epilepsy may have
characteristics suggesting frontal lobe impairment. The educational and social impairments
associated with the epilepsy syndromes of childhood and adolescence are of major
importance but they have been the subject of remarkably few well-performed studies. The
impairments are not always necessarily permanent and it seems highly likely that the
cognitive and behavioural outcome of at least some of these syndromes can be influenced
greatly by early effective treatment with either antiepileptic medication or surgery
586. Besag FM. Behavioral aspects of pediatric epilepsy syndromes. Epilepsy Behav 2004;5
Suppl 1:S3-13.
Ref ID: 4616
Abstract: Apart from control of the seizures, two of the most important factors in
determining how well a child with epilepsy progresses toward independence are cognition
and behavior. The diagnosis of the correct epilepsy syndrome often provides information
with regard to probability of good seizure control and intellectual outcome. However,
relatively little has been published on the behavioral aspects of the various epilepsy
syndromes. In West syndrome there is emerging evidence that early effective treatment
might improve outcome in terms of both cognition and behavior. The work on this syndrome
in children with tuberous sclerosis has demonstrated an association between temporal lobe
tubers and autism. In Dravet syndrome, a variety of psychiatric disorders have been
reported, including hyperactivity and autistic features. This is another epilepsy syndrome
that tends to be resistant to treatment, implying that the prognosis has to be guarded. The
behavioral problems reported with Lennox-Gastaut syndrome also include autistic features,
as well as generally sluggish behavior. It is very likely that these characteristics largely
reflect the effect of ongoing seizure activity. Autistic features, aggression, and hyperkinesis
have been described with Landau-Kleffner syndrome. The behavior may improve
dramatically with appropriate medical treatment or after multiple subpial transection.
Although the syndrome of benign partial seizures with centrotemporal or rolandic spikes is
said to have a very good prognosis, it is becoming increasingly evident that behavioral
problems such as concentration difficulties, tempers, hyperactivity, and impulsivity might
occur. Juvenile myoclonic epilepsy has been associated with very variable behavioral traits,
144
sometimes with immature personality features and poor social adjustment suggesting
frontal lobe dysfunction. Because many of the reports of behavioral disturbance associated
with epilepsy syndromes are anecdotal and do not include validated measures of behavior
it would be unwise to draw firm conclusions from them at this stage. Carefully conducted
prospective studies, paying particular attention to any behavioral improvements that occur
with successful treatment of the epilepsy, are required
587. Bess FH. Audiometric approaches used in the identification of middle ear disease in
children. In: Kavanagh JF, editor. Otitis Media and Child Development. Parkton, MD: York
Press; 1986:70-82.
Ref ID: 875
588. Bess FH, Tharpe AM. Unilateral hearing impairment in children. Pediatrics
1984;74:206-216.
Ref ID: 768
589. Bess FH. Hearing loss associated with middle ear effusion: Workshop on effects of otitis
media on the child. Pediatrics 1983;71:640-641.
Ref ID: 586
590. Best CA, Minshew NJ, Strauss MS. Gender discrimination of eyes and mouths by
individuals with autism. Autism Res 2010;3(2):88-93.
Ref ID: 6646
Abstract: Evidence remains mixed about whether individuals with autism look less to eyes
and whether they look more at mouths. Few studies have examined how spontaneous
attention to facial features relates to face processing abilities. This study tested the ability to
discriminate gender from facial features, namely eyes and mouths, by comparing accuracy
scores of 17 children with autism and 15 adults with autism to 17 typically developing
children and 15 typically developing adults. Results indicated that all participants regardless
of diagnosis discriminated gender more accurately from eyes than from mouths. However,
results indicated that compared to adults without autism, adults with autism were
significantly worse at discriminating gender from eyes
591. Best CS, Moffat VJ, Power MJ, Owens DG, Johnstone EC. The boundaries of the cognitive
phenotype of autism: Theory of Mind, Central Coherence and Ambiguous Figure
Perception in young people with autistic traits. J Autism Dev Disord 2007.
Ref ID: 5406
Abstract: Theory of Mind, Weak Central Coherence and executive dysfunction, were
investigated as a function of behavioural markers of autism. This was irrespective of the
presence or absence of a diagnosis of an autistic spectrum disorder. Sixty young people
completed the Social Communication Questionnaire (SCQ), false belief tests, the block
design test, viewed visual illusions and an ambiguous figure. A logistic regression was
performed and it was found that Theory of Mind, central coherence and ambiguous figure
variables significantly contributed to prediction of behavioural markers of autism. These
findings provide support for the continuum hypothesis of autism. That is, mild autistic
behavioural traits are distributed through the population and these behavioural traits may
have the same underlying cognitive determinants as autistic disorder
592. Best JR, Miller PH. A developmental perspective on executive function. Child Dev
2010;81(6):1641-1660.
Ref ID: 7501
Abstract: This review article examines theoretical and methodological issues in the
construction of a developmental perspective on executive function (EF) in childhood and
adolescence. Unlike most reviews of EF, which focus on preschoolers, this review focuses
on studies that include large age ranges. It outlines the development of the foundational
components of EF-inhibition, working memory, and shifting. Cognitive and
145
neurophysiological assessments show that although EF emerges during the first few years
of life, it continues to strengthen significantly throughout childhood and adolescence. The
components vary somewhat in their developmental trajectories. The article relates the
findings to long-standing issues of development (e.g., developmental sequences,
trajectories, and processes) and suggests research needed for constructing a
developmental framework encompassing early childhood through adolescence
593. Best JR, Miller PH, Jones LL. Executive Functions after Age 5: Changes and Correlates.
Dev Rev 2009;29(3):180-200.
Ref ID: 7502
Abstract: Research and theorizing on executive function (EF) in childhood has been
disproportionately focused on preschool age children. This review paper outlines the
importance of examining EF throughout childhood, and even across the lifespan. First,
examining EF in older children can address the question of whether EF is a unitary
construct. The relations among the EF components, particularly as they are recruited for
complex tasks, appear to change over the course of development. Second, much of the
development of EF, especially working memory, shifting, and planning, occurs after age 5.
Third, important applications of EF research concern the role of school-age children's EF in
various aspects of school performance, as well as social functioning and emotional control.
Future research needs to examine a more complete developmental span, from early
childhood through late adulthood, in order to address developmental issues adequately
594. Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic
and genomic disorders and still counting. Brain Res 2011;1380:42-77.
Ref ID: 7004
Abstract: There is increasing evidence that autism spectrum disorders (ASDs) can arise
from rare highly penetrant mutations and genomic imbalances. The rare nature of these
variants, and the often differing orbits of clinical and research geneticists, can make it
difficult to fully appreciate the extent to which we have made progress in understanding the
genetic etiology of autism. In fact, there is a persistent view in the autism research
community that there are only a modest number of autism loci known. We carried out an
exhaustive review of the clinical genetics and research genetics literature in an attempt to
collate all genes and recurrent genomic imbalances that have been implicated in the
etiology of ASD. We provide data on 103 disease genes and 44 genomic loci reported in
subjects with ASD or autistic behavior. These genes and loci have all been causally
implicated in intellectual disability, indicating that these two neurodevelopmental disorders
share common genetic bases. A genetic overlap between ASD and epilepsy is also
apparent in many cases. Taken together, these findings clearly show that autism is not a
single clinical entity but a behavioral manifestation of tens or perhaps hundreds of genetic
and genomic disorders. Increased recognition of the etiological heterogeneity of ASD will
greatly expand the number of target genes for neurobiological investigations and thereby
provide additional avenues for the development of pathway-based pharmacotherapy.
Finally, the data provide strong support for high-resolution DNA microarrays as well as
whole-exome and whole-genome sequencing as critical approaches for identifying the
genetic causes of ASDs
595. Betancur C. Etiological heterogeneity in autism spectrum disorders: More than 100 genetic
and genomic disorders and still counting. Brain Res 2010.
Ref ID: 6843
Abstract: There is increasing evidence that autism spectrum disorders (ASDs) can arise
from rare highly penetrant mutations and genomic imbalances. The rare nature of these
variants, and the often differing orbits of clinical and research geneticists, can make it
difficult to fully appreciate the extent to which we have made progress in understanding the
genetic etiology of autism. In fact, there is a persistent view in the autism research
community that there are only a modest number of autism loci known. We carried out an
exhaustive review of the clinical genetics and research genetics literature in an attempt to
146
collate all genes and recurrent genomic imbalances that have been implicated in the
etiology of ASD. We provide data on 103 disease genes and 44 genomic loci reported in
subjects with ASD or autistic behavior. These genes and loci have all been causally
implicated in intellectual disability, indicating that these two neurodevelopmental disorders
share common genetic bases. A genetic overlap between ASD and epilepsy is also
apparent in many cases. Taken together, these findings clearly show that autism is not a
single clinical entity but a behavioral manifestation of tens or perhaps hundreds of genetic
and genomic disorders. Increased recognition of the etiological heterogeneity of ASD will
greatly expand the number of target genes for neurobiological investigations and thereby
provide additional avenues for the development of pathway-based pharmacotherapy.
Finally, the data provide strong support for high-resolution DNA microarrays as well as
whole-exome and whole-genome sequencing as critical approaches for identifying the
genetic causes of ASDs
596. Bethea TC, Sikich L. Early pharmacological treatment of autism: a rationale for
developmental treatment. Biol Psychiatry 2007;61(4):521-537.
Ref ID: 7277
Abstract: Autism is a dynamic neurodevelopmental syndrome in which disabilities emerge
during the first three postnatal years and continue to evolve with ongoing development. We
briefly review research in autism describing subtle changes in molecules important in brain
development and neurotransmission, in morphology of specific neurons, brain connections,
and in brain size. We then provide a general schema of how these processes may interact
with particular emphasis on neurotransmission. In this context, we present a rationale for
utilizing pharmacologic treatments aimed at modifying key neurodevelopmental processes
in young children with autism. Early treatment with selective serotonin reuptake inhibitors
(SSRIs) is presented as a model for pharmacologic interventions because there is evidence
in autistic children for reduced brain serotonin synthesis during periods of peak
synaptogenesis; serotonin is known to enhance synapse refinement; and exploratory
studies with these agents in autistic children exist. Additional hypothetical developmental
interventions and relevant published clinical data are described. Finally, we discuss the
importance of exploring early pharmacologic interventions within multiple experimental
settings in order to develop effective treatments as quickly as possible while minimizing
risks
597. Bette S, Zimmermann U, Wissinger B, Knipper M. OPA1, the disease gene for optic
atrophy type Kjer, is expressed in the inner ear. Histochem Cell Biol 2007;128(5):421-430.
Ref ID: 6278
Abstract: Autosomal dominant optic atrophy (adOA) is the most common form of hereditary
optic neuropathy. The majority of cases are associated with mutations in the OPA1 gene. A
few cases of adOA are known to be associated with moderate progressive hearing loss. To
gain insight into the pathogenesis of this hearing loss, we performed expression analyses
of OPA1 in the rat auditory and vestibular organ. In cochlear tissue, several splice variants
of OPA1 were detected, which are also expressed in retinal tissue. OPA1 mRNA and
protein was found in the hair cells and ganglion cells of the cochlea and vestibular organ. In
ganglion cells, OPA1 mRNA and protein was already detectable at birth, whereas in the
organ of Corti OPA1 mRNA and protein was up-regulated after birth and reached
mature-like expression level during the onset of hearing. Comparison of an antibody
directed to the mitochondrial marker protein HSP60 with antibodies directed to different
amino acid stretches of OPA1 revealed a sub-cellular distribution of OPA1 in areas of
significant density of mitochondria. The data suggest that defects in OPA1 cause hearing
disorders due to a progressing metabolic disturbance of hair and ganglion cells in the inner
ear
598. Bettelheim B. The Empty Fortress. New York: The Free Press; 1967.
Ref ID: 121
147
599. Bettison S. The long-term effects of auditory training on children with autism. J Autism Dev
Disord 1996;26(3):361-374.
Ref ID: 4250
Abstract: Eighty children, 3-17 years of age, with autism or Asperger syndrome and mild to
severe distress in the presence of some sounds, were randomly allocated to two groups.
The experimental group received auditory training and the control group listened to the
same unmodified music under the same conditions. Significant improvements in behavior
and severity of autism were maintained for 12 months by both groups. Informal data
suggested that a range of abnormal responses to sound and other sensory abnormalities
may also have improved. Verbal and performance IQ increased significantly 3 to 12 months
after interventions. Findings suggest that some aspect of both auditory training and
listening to selected unmodified music may have a beneficial effect on children with autism
and sound sensitivity, and indicate a need for further research into the effects that led to
these changes and the mechanisms involved in the sensory abnormalities commonly
associated with autism
600. Beukelman D, Mirenda P. Augmentative and alternatlive communicatin: management of
severe communication disorders in children and adults. 2 ed. Baltimore, MD.: Paul
H.Brookes; 1998.
Ref ID: 4289
601. Bever T, Montalbetti M. Linguistics. Noam's Ark. Science 2002;298(5598):1565-1566.
Ref ID: 3748
602. Beversdorf DQ, Manning SE, Hillier A et al. Timing of prenatal stressors and autism. J
Autism Dev Disord 2005;35(4):471-478.
Ref ID: 5224
Abstract: Recent evidence supports a role for genetics in autism, but other findings are
difficult to reconcile with a purely genetic cause. Pathological changes in the cerebellum in
autism are thought to correspond to an event before 30-32 weeks gestation. Our purpose
was to determine whether there is an increased incidence of stressors in autism before this
time period. Surveys regarding incidence and timing of prenatal stressors were distributed
to specialized schools and clinics for autism and Down syndrome, and to mothers of
children without neurodevelopmental diagnoses in walk-in clinics. Incidence of stressors
during each 4-week block of pregnancy was recorded. Incidence of stressors in the blocks
prior to and including the predicted time period (21-32 weeks gestation) in each group of
surveys was compared to the other prenatal blocks. A higher incidence of prenatal
stressors was found in autism at 21-32 weeks gestation, with a peak at 25-28 weeks. This
does support the possibility of prenatal stressors as a potential contributor to autism, with
the timing of stressors consistent with the embryological age suggested by
neuroanatomical findings seen in the cerebellum in autism. Future prospective studies
would be needed to confirm this finding
603. Beversdorf DQ, Anderson JM, Manning SE et al. Brief report: macrographia in
high-functioning adults with autism spectrum disorder. J Autism Dev Disord
2001;31(1):97-101.
Ref ID: 3797
Abstract: The initial description of Asperger syndrome commented on the poor handwriting
and motor coordination difficulties of individuals with this condition. Early descriptions of
autism do not remark upon such difficulties. Recent evidence, however, suggests that
individuals with both conditions have a similar motor control impairment. Handwriting has
not been formally assessed in this context. Our study compared handwriting size between
individuals with autism spectrum disorder and age- and IQ-matched control subjects.
Macrographia was observed among subjects with autism spectrum disorder which
remained statistically significant when covaried with educational level. This finding may
148
correlate with the anatomical abnormalities present in the cerebellum of individuals with
autism spectrum disorder
604. Bianchi C, Giammusso V, Berti N, Vassallo A. [Medulloblastoma in a patient with
xeroderma pigmentosum]. Pathologica 1979;71(1015):697-701.
Ref ID: 3740
605. Biederman J, Faraone SV, Mick E et al. High risk of attention deficit hyperactivity disorder
among children of parents with childhood onset of the disorder: A pilot study. Am J
Psychiatry 1995;152:431-435.
Ref ID: 1435
606. Biederman J, Milberger S, Faraone SV et al. Family-environment risk factors for
attention-deficit hyperactivity disorder. A test of Rutter's indicators of adversity. Arch Gen
Psychiatry 1995;52(6):464-470.
Ref ID: 6884
Abstract: BACKGROUND: This study investigated whether family-environment risk factors
are associated with attention-deficit hyperactivity disorder (ADHD). Compelling work by
Rutter and coworkers revealed that it was the aggregate of adversity factors (severe marital
discord, low social class, large family size, paternal criminality, maternal mental disorder,
and foster care placement) rather than the presence of any single factor that led to
impaired development. Based on the work of Rutter, we hypothesized a positive
association between indicators of adversity and the diagnosis of ADHD and
ADHD-associated impairments. METHODS: We studied 140 ADHD and 120 normal control
probands. Subjects were non-Hispanic white boys between the ages of 6 and 17 years.
Rutter's indicators of adversity were used to predict ADHD-related psychopathology as well
as impaired cognitive and psychosocial functioning. RESULTS: The odds ratio for the
diagnosis of ADHD increased as the number of Rutter's adversity index predicted
ADHD-related psychopathology (depression, anxiety, and conduct disorder), learning
disabilities, cognitive impairment, and psychosocial dysfunction. CONCLUSIONS: A
positive association appears to exist between adversity indicators and the risk for ADHD as
well as for its associated psychiatric, cognitive, and psychosocial impairments. These
findings support the work of Rutter and stress the importance of adverse
family-environment variables as risk factors for children with ADHD
607. Biederman J, Munir K, Knee D et al. A family study of patients with attention deficit disorder
and normal controls. J Psychiat Res 1986;4:263-274.
Ref ID: 259
Abstract: In a family study of Attention Deficit Disorder (ADD), we collected data on
first-degree relatives of 22 children with ADD and 20 normal children. The morbidity risk for
ADD was 31.5% in the first group. This was significantly higher than the rate of 5.7% in the
control group. Relatives of ADD probands were also shown to be at higher risk for
Oppositional Disorders and Major Depressive Disorder (MDD). The findings indicate that
ADD is a familial disorder associated with increased familial risk of other psychiatric
disorders
608. Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ. Profound impairment in social
recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout
mice. Neuropsychopharmacology 2004;29(3):483-493.
Ref ID: 4486
Abstract: Considerable evidence suggests that arginine vasopressin (AVP) is critically
involved in the regulation of many social and nonsocial behaviors, including emotionality.
The existence of two AVP receptors in the brain, namely the V1a and V1b subtypes, and
the lack of clear pharmacological data using selective agonists or antagonists, make it
difficult to determine which receptor is responsible for the AVP-mediated effects on
behavior. Here we report the behavioral effects of a null mutation in the V1a receptor
149
(V1aR) in male mice. Male mice lacking functional V1aR (V1aRKO) exhibit markedly
reduced anxiety-like behavior and a profound impairment in social recognition. V1aRKO
performed normally on spatial and nonsocial olfactory learning and memory tasks. Acute
central administration of AVP robustly stimulated stereotypical scratching and
autogrooming in wild-type (WT), but not V1aRKO males. AVP and oxytocin (OT) mRNA
and OT receptor-binding levels were similar in WT and V1aRKO mice. Given the current
findings, the V1aR may provide a novel potential pharmacological target for social and
affective disorders including autism, and anxiety disorders
609. Bigham M, Copes R, Srour L. Exposure to thimerosal in vaccines used in Canadian infant
immunization programs, with respect to risk of neurodevelopmental disorders. Can
Commun Dis Rep 2002;28(9):69-80.
Ref ID: 3641
610. Bigler ED, Mortensen S, Neeley ES et al. Superior temporal gyrus, language function, and
autism. Dev Neuropsychol 2007;31(2):217-238.
Ref ID: 5100
Abstract: Deficits in language are a core feature of autism. The superior temporal gyrus
(STG) is involved in auditory processing, including language, but also has been implicated
as a critical structure in social cognition. It was hypothesized that subjects with autism
would display different size-function relationships between the STG and
intellectual-language-based abilities when compared to controls. Intellectual ability was
assessed by either the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) or
Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), where three intellectual
quotients (IQ) were computed: verbal (VIQ), performance (PIQ), and full-scale (FSIQ).
Language ability was assessed by the Clinical Evaluation of Language Fundamentals-Third
Edition (CELF-3), also divided into three index scores: receptive, expressive, and total.
Seven to 19-year-old rigorously diagnosed subjects with autism (n = 30) were compared to
controls (n = 39; 13 of whom had a deficit in reading) of similar age who were matched on
education, PIQ, and head circumference. STG volumes were computed based on 1.5 Tesla
magnetic resonance imaging (MRI). IQ and CELF-3 performance were highly interrelated
regardless of whether subjects had autism or were controls. Both IQ and CELF-3 ability
were positively correlated with STG in controls, but a different pattern was observed in
subjects with autism. In controls, left STG gray matter was significantly (r = .42, p < or =
.05) related to receptive language on the CELF-3; in contrast, a zero order correlation was
found with autism. When plotted by age, potential differences in growth trajectories related
to language development associated with STG were observed between controls and those
subjects with autism. Taken together, these findings suggest a possible failure in left
hemisphere lateralization of language function involving the STG in autism
611. Bijlsma EK, Gijsbers AC, Schuurs-Hoeijmakers JH et al. Extending the phenotype of
recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism
and in normal individuals. Eur J Med Genet 2009;52(2-3):77-87.
Ref ID: 6524
Abstract: Array CGH (comparative genomic hybridization) screening of large patient
cohorts with mental retardation and/or multiple congenital anomalies (MR/MCA) has led to
the identification of a number of new microdeletion and microduplication syndromes.
Recently, a recurrent copy number variant (CNV) at chromosome 16p11.2 was reported to
occur in up to 1% of autistic patients in three large autism studies. In the screening of 4284
patients with MR/MCA with various array platforms, we detected 22 individuals (14 index
patients and 8 family members) with deletions in 16p11.2, which are genomically identical
to those identified in the autism studies. Though some patients shared a facial resemblance
and a tendency to overweight, there was no evidence for a recognizable phenotype. Autism
was not the presenting feature in our series. The assembled evidence indicates that
recurrent 16p11.2 deletions are associated with variable clinical outcome, most likely
150
arising from haploinsufficiency of one or more genes. The phenotypical spectrum ranges
from MR and/or MCA, autism, learning and speech problems, to a normal phenotype
612. Biklen D. Communication unbound: Autism and praxis. Harvard Educ Rev
1990;60:291-314.
Ref ID: 278
613. Bilder D, Pinborough-Zimmerman J, Miller J, McMahon W. Prenatal, perinatal, and
neonatal factors associated with autism spectrum disorders. Pediatrics
2009;123(5):1293-1300.
Ref ID: 6555
Abstract: OBJECTIVE: To investigate prenatal, perinatal, and neonatal risk factors for
autism spectrum disorders by using participants identified through broad ascertainment and
reliable classification methods. METHODS: The targeted population was 8-year-old
children born in 1994 and residing in 1 of the 3 most populous counties in Utah who were
identified as having an autism spectrum disorder on the basis of methodology used by the
2002 Autism and Developmental Disabilities Monitoring Network. Of those identified, 132
children (115 boys, 17 girls) had birth certificate records available. Each child was matched
by gender and birth year to 100 controls (11 500 boys, 1700 girls) from the birth certificate
database in a nested case-control design. Birth certificate records of participants and
controls were surveyed for 23 potentially pathologic prenatal, perinatal, and neonatal
factors. RESULTS: The prenatal factors that occurred significantly more frequently among
children with autism spectrum disorders were advanced maternal age and parity. Increased
duration of education among mothers of children with autism spectrum disorders was small
but statistically significant. Significant perinatal factors were breech presentation and
primary cesarean delivery. When corrected for breech presentation, a known indication for
cesarean delivery, the association between primary cesarean delivery and autism spectrum
disorders was eliminated. There were no significant associations found between autism
spectrum disorders and neonatal factors. CONCLUSIONS: In the absence of other
complications suggesting fetal distress, the association between breech presentation and
autism spectrum disorders in this study suggests a shared etiology rather than causal
relationship. Additional investigation focused on both genetic and environmental factors
that link these autism spectrum disorder risk factors individually or collectively is needed
614. Bill BR, Geschwind DH. Genetic advances in autism: heterogeneity and convergence on
shared pathways. Curr Opin Genet Dev 2009;19(3):271-278.
Ref ID: 6616
Abstract: The autism spectrum disorders (ASD) are a heterogeneous set of developmental
disorders characterized at their core by deficits in social interaction and communication.
Current psychiatric nosology groups this broad set of disorders with strong genetic liability
and multiple etiologies into the same diagnostic category. This heterogeneity has
challenged genetic analyses. But shared patient resources, genomic technologies, more
refined phenotypes, and novel computational approaches have begun to yield dividends in
defining the genetic mechanisms at work. Over the last five years, a large number of autism
susceptibility loci have emerged, redefining our notion of autism's etiologies, and reframing
how we think about ASD
615. Billard C, Autret A, Laffont F, Lucas B, Degiovanni E. Electrical status epilepticus during
sleep in children: a reappraisal from eight new cases. In: Sterman MB, Shouse MN,
Passouant P, editors. Sleep and Epilepsy. Orlando,FL: Academic Press; 1982:481-494.
Ref ID: 434
616. Billeci L, Calderoni S, Tosetti M, Catani M, Muratori F. White matter connectivity in children
with autism spectrum disorders: a tract-based spatial statistics study. BMC Neurol
2012;12:148.
Ref ID: 7566
151
Abstract: BACKGROUND: Autism spectrum disorders (ASD) are associated with
widespread alterations in white matter (WM) integrity. However, while a growing body of
studies is shedding light on microstructural WM alterations in high-functioning adolescents
and adults with ASD, literature is still lacking in information about whole brain structural
connectivity in children and low-functioning patients with ASD. This research aims to
investigate WM connectivity in ASD children with and without mental retardation compared
to typically developing controls (TD). METHODS: Diffusion tensor imaging (DTI) was
performed in 22 young children with ASD (mean age: 5.54 years) and 10 controls (mean
age: 5.25 years). Data were analysed both using the tract-based spatial statistics (TBSS)
and the tractography. Correlations were investigated between the WM microstructure in the
identified altered regions and the productive language level. RESULTS: The TBSS analysis
revealed widespread increase of fractional anisotropy (FA) in major WM pathways. The
tractographic approach showed an increased fiber length and FA in the cingulum and in the
corpus callosum and an increased mean diffusivity in the indirect segments of the right
arcuate and the left cingulum. Mean diffusivity was also correlated with expressive
language functioning in the left indirect segments of the arcuate fasciculus.
CONCLUSIONS: Our study confirmed the presence of several structural connectivity
abnormalities in young ASD children. In particular, the TBSS profile of increased FA that
characterized the ASD patients extends to children a finding previously detected in ASD
toddlers only. The WM integrity abnormalities detected may be relevant to the
pathophysiology of ASD, since the structures involved participate in some core atypical
characteristics of the disorder
617. Billstedt E, Carina G, I, Gillberg C. Autism in adults: symptom patterns and early childhood
predictors. Use of the DISCO in a community sample followed from childhood. J Child
Psychol Psychiatry 2007;48(11):1102-1110.
Ref ID: 5408
Abstract: Background: Few studies have looked at the very long-term outcome of
individuals with autism who were diagnosed in childhood. Methods: A longitudinal,
prospective, community-based follow-up study of adults who had received the diagnosis of
autism (classic and atypical) in childhood (n = 105) was conducted. A structured interview
(the Diagnostic Interview for Social and COmmunication disorders - the DISCO) was used
in order to evaluate symptoms and symptom patterns 13-22 years after original diagnosis.
Childhood measures, including IQ-level at time of childhood diagnosis and communicative
speech registered before age 5 years, were studied in relation to the presence of autism
symptoms at follow-up. Results: The classical and atypical autism groups were fairly
homogeneously impaired in terms of symptoms in the social interaction category whereas
other common childhood autism symptoms, including maladaptive and stereotyped
behaviours, were more variable in the study group at follow-up. Odd responses to sensory
stimuli were still extremely common. Speech before 5 years of age, IQ, gender, diagnosed
medical disorder and onset of epilepsy before 5 years were variables that correlated to
outcome on the DISCO algorithm for autistic spectrum disorders (Wing & Gould, 1979)
concerning style and quality of social interaction, communication style and pattern of
self-chosen activities. Conclusions: Social interaction problems were still present in the vast
majority of adults with autism/atypical autism, but behavioural impairments were much
more variable in adulthood. Almost all cases were reported to show persistent perceptual
problems. Certain childhood measures were found to prospectively predict adult social
interaction style, communication type, and pattern of self-chosen activities, which still met
diagnostic criteria for autism/atypical autism in adulthood
618. Binbay T, Drukker M, Elbi H et al. Testing the psychosis continuum: differential impact of
genetic and nongenetic risk factors and comorbid psychopathology across the entire
spectrum of psychosis. Schizophr Bull 2012;38(5):992-1002.
Ref ID: 7627
Abstract: A growing number of studies demonstrate high rates of subthreshold psychotic
experiences, but there is considerable heterogeneity in rates due to study cohort and
152
design factors, obscuring how prevalent psychotic experiences may or may not relate to
rare psychotic disorders. In a representative general population sample (n = 4011) in Izmir,
Turkey, the full spectrum of expression of psychosis was categorized across 5 groups
representing (1) absence of psychosis, (2) subclinical psychotic experiences, (3)
low-impact psychotic symptoms, (4) high-impact psychotic symptoms, and (5) full-blown
clinical psychotic disorder and analyzed for continuity and discontinuity in relation to (1)
other symptom dimensions associated with psychotic disorder and (2) proxies of genetic
and nongenetic etiology. Results were tested for linear and extralinear contrasts between
clinical and nonclinical and between disorder and nondisorder expression of psychosis.
Demographic variables, indexing premorbid social adjustment and socioeconomic status,
impacted mostly linearly; proxy variables of genetic loading (more or more severely
affected relatives) impacted in a positive extralinear fashion; environmental risk factors
sometimes impacted linearly (urbanicity and childhood adversity) and sometimes
extralinearly (cannabis), occasioning a disproportional shift in risk at the clinical disorder
end of the spectrum. Affective symptoms were associated with a disproportionally higher
risk below the disorder threshold, whereas a disproportionally higher risk above the
threshold was associated with psychotic symptom load, negative symptoms,
disorganization, and visible signs of mental illness. Liability associated with respectively
affective and nonaffective symptom domains, in interaction with environmental risks, may
operate by impacting differentially over a quasi-continuous extended psychosis phenotype
in the population
619. Binder JR. Comments on a case of pure word deafness. JINS 2005;11(4):455.
Ref ID: 4564
620. Bindoff L. Treatment of mitochondrial disorders: practical and theoretical issues. Eur J
Paediatr Neurol 1999;3(5):201-208.
Ref ID: 2759
621. Bingham PM, Spinner NB, Sovinsky L, Zackai EH, Chance PF. Infantile spasms associated
with proximal duplication of chromosome 15q. Pediatr Neurol 1996;15(2):163-165.
Ref ID: 3489
Abstract: We describe a case of infantile spasms associated with a chromosome
abnormality (supernumerary inverted duplication of chromosome 15 [47,XX,+inv dup(15)]).
The patient was nondysmorphic and presented with mild hypotonia and delay in acquisition
of gross motor milestones before the diagnosis of seizures at age 7 months. Additional
features included unilateral sensorineural deafness and torticollis. Molecular cytogenetic
studies confirmed that the patient has a large inv dup(15). Inv dup(15) chromosomes are
variable with respect to the size and genetic composition of the chromosome and in their
phenotypic effects. Patients with small inv dup(15s) may have no phenotypic abnormalities,
whereas patients with large inv dup(15s) may have multiple abnormalities. ACTH therapy
resulted in prompt remission of seizures and resolution of EEG abnormalities. This is the
second report of a patient with IS and a supernumerary inv dup(15). Several genes code
for neurotransmitter receptor subunits located in the duplicated region of chromosome 15,
and abnormal dosage of these genes may be involved in the genesis of seizure activity in
carriers of the inv dup(15). Chromosome analysis may lead to a specific diagnosis in
infants with unexplained infantile spasms
622. Bird HR, Gould MS, Staghezza B. Aggregating data from multiple informants in child
psychiatry epidemiological research. J Am Acad Child Adolesc Psychiatry 1992;1:78-85.
Ref ID: 410
623. Bird J, Bishop D. Perception and awareness of phonemes in phonologically impaired
children. Eur J Disord Communic 1992;27:289-311.
Ref ID: 1591
153
624. Bishop DV. Overlaps between autism and language impairment: phenomimicry or shared
etiology? Behav Genet 2010;40(5):618-629.
Ref ID: 6929
Abstract: Traditionally, autistic spectrum disorder (ASD) and specific language impairment
(SLI) are regarded as distinct conditions with separate etiologies. Yet these disorders
co-occur at above chance levels, suggesting shared etiology. Simulations, however, show
that additive pleiotropic genes cannot account for observed rates of language impairment in
relatives, which are higher for probands with SLI than for those with ASD + language
impairment. An alternative account is in terms of 'phenomimicry', i.e., language impairment
in comorbid cases may be a consequence of ASD risk factors, and different from that seen
in SLI. However, this cannot explain why molecular genetic studies have found a common
risk genotype for ASD and SLI. This paper explores whether nonadditive genetic influences
could account for both family and molecular findings. A modified simulation involving G x G
interactions obtained levels of comorbidity and rates of impairment in relatives more
consistent with observed values. The simulations further suggest that the shape of
distributions of phenotypic trait scores for different genotypes may provide evidence of
whether a gene is involved in epistasis
625. Bishop DV. Which neurodevelopmental disorders get researched and why? PLoS One
2010;5(11):e15112.
Ref ID: 7578
Abstract: AIM: There are substantial differences in the amount of research concerned with
different disorders. This paper considers why. METHODS: Bibliographic searches were
conducted to identify publications (1985-2009) concerned with 35 neurodevelopmental
disorders: Developmental dyslexia, Developmental dyscalculia, Developmental
coordination disorder, Speech sound disorder, Specific language impairment, Attention
deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual
disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat
syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome,
Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe
syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome,
Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome,
Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams
syndrome, XXX and XYY. A publication index reflecting N publications relative to
prevalence was derived. RESULTS: The publication index was higher for rare than
common conditions. However, this was partly explained by the tendency for rare disorders
to be more severe. INTERPRETATION: Although research activity is predictable from
severity and prevalence, there are exceptions. Low rates of research, and relatively low
levels of NIH funding, characterise conditions that are the domain of a single discipline with
limited research resources. Growth in research is not explained by severity, and was
exceptionally steep for autism and ADHD
626. Bishop DV. Genes, cognition, and communication: insights from neurodevelopmental
disorders. Ann N Y Acad Sci 2009;1156:1-18.
Ref ID: 6932
Abstract: Twin and family studies have demonstrated that most cognitive traits are
moderately to highly heritable. Neurodevelopmental disorders such as dyslexia, autism,
and specific language impairment (SLI) also show strong genetic influence. Nevertheless, it
has proved difficult for researchers to identify genes that would explain substantial amounts
of variance in cognitive traits or disorders. Although this observation may seem
paradoxical, it fits with a multifactorial model of how complex human traits are influenced by
numerous genes that interact with one another, and with the environment, to produce a
specific phenotype. Such a model can also explain why genetic influences on cognition
have not vanished in the course of human evolution. Recent linkage and association
studies of SLI and dyslexia are reviewed to illustrate these points. The role of nonheritable
genetic mutations (sporadic copy number variants) in causing autism is also discussed.
154
Finally, research on phenotypic correlates of allelic variation in the genes ASPM and
microcephalin is considered; initial interest in these as genes for brain size or intelligence
has been dampened by a failure to find phenotypic differences in people with different
versions of these genes. There is a current vogue for investigators to include measures of
allelic variants in studies of cognition and cognitive disorders. It is important to be aware
that the effect sizes associated with these variants are typically small and hard to detect
without extremely large sample sizes
627. Bishop DV. Using mismatch negativity to study central auditory processing in
developmental language and literacy impairments: Where are we, and where should we be
going? Psychol Bull 2007;133(4):651-672.
Ref ID: 5048
Abstract: A popular theoretical account of developmental language and literacy disorders
implicates poor auditory temporal processing in their etiology, but evidence from studies
using behavioral measures has yielded inconsistent results. The mismatch negativity
(MMN) component of the auditory event-related potential has been recommended as an
alternative, relatively objective, measure of the brain's ability to discriminate sounds that is
suitable for children with limited attention or motivation. A literature search revealed 26
studies of the MMN in individuals with dyslexia or specific language impairment and 4
studies of infants or children at familial risk of these disorders. Findings were highly
inconsistent. Overall, attenuation of the MMN and atypical lateralization in the clinical group
were most likely to be found in studies using rapidly presented stimuli, including nonverbal
sounds. The MMN literature offers tentative support for the hypothesis that auditory
temporal processing is impaired in language and literacy disorders, but the field is plagued
by methodological inconsistencies, low reliability of measures, and low statistical power.
The article concludes with recommendations for improving this state of affairs. ((c) 2007
APA, all rights reserved)
628. Bishop DV, Hayiou-Thomas ME. Heritability of specific language impairment depends on
diagnostic criteria. Genes Brain Behav 2007.
Ref ID: 5443
Abstract: Heritability estimates for specific language impairment (SLI) have been
inconsistent. Four twin studies reported heritability of 0.5 or more, but a recent report from
the Twins Early Development Study found negligible genetic influence in 4-year-olds. We
considered whether the method of ascertainment influenced results and found substantially
higher heritability if SLI was defined in terms of referral to speech and language pathology
services than if defined by language test scores. Further analysis showed that presence of
speech difficulties played a major role in determining whether a child had contact with
services. Childhood language disorders that are identified by population screening are
likely to have a different phenotype and different etiology from clinically referred cases.
Genetic studies are more likely to find high heritability if they focus on cases who have
speech difficulties and who have been referred for intervention
629. Bishop DV, Hardiman M, Uwer R, von SW. Atypical long-latency auditory event-related
potentials in a subset of children with specific language impairment
36. Dev Sci 2007;10(5):576-587.
Ref ID: 7304
Abstract: It has been proposed that specific language impairment (SLI) is the consequence
of low-level abnormalities in auditory perception. However, studies of long-latency auditory
ERPs in children with SLI have generated inconsistent findings. A possible reason for this
inconsistency is the heterogeneity of SLI. The intraclass correlation (ICC) has been
proposed as a useful statistic for evaluating heterogeneity because it allows one to
compare an individual's auditory ERP with the grand average waveform from a typically
developing reference group. We used this method to reanalyse auditory ERPs from a
sample previously described by Uwer, Albrecht and von Suchodoletz (2002). In a subset of
children with receptive SLI, there was less correspondence (i.e. lower ICC) with the
155
normative waveform (based on the control grand average) than for typically developing
children. This poorer correspondence was seen in responses to both tone and speech
stimuli for the period 100-228 ms post stimulus onset. The effect was lateralized and seen
at right- but not left-sided electrodes
630. Bishop DV. Developmental cognitive genetics: how psychology can inform genetics and
vice versa. Quarterly Journal of Experimental Psychology (Colchester)
2006;59(7):1153-1168.
Ref ID: 5042
Abstract: Developmental neuropsychology is concerned with uncovering the underlying
basis of developmental disorders such as specific language impairment (SLI),
developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic
influences play an important part in the aetiology of all of these disorders, yet progress in
identifying genes has been slow. One way forward is to cut loose from conventional clinical
criteria for diagnosing disorders and to focus instead on measures of underlying cognitive
mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for
heritable phenotypes. However, it is not a one-way street. By using genetically informative
designs, one can gain insights about causal relationships between different cognitive
deficits. For instance, it has been suggested that low-level auditory deficits cause
phonological problems in SLI. However, a twin study showed that, although both types of
deficit occur in SLI, they have quite different origins, with environmental factors more
important for auditory deficit, and genes more important for deficient phonological
short-term memory. Another study found that morphosyntactic deficits in SLI are also highly
heritable, but have different genetic origins from impairments of phonological short-term
memory. A genetic perspective shows that a search for the underlying cause of
developmental disorders may be misguided, because they are complex and heterogeneous
and are associated with multiple risk factors that only cause serious disability when they
occur in combination
631. Bishop DV, Adams CV, Norbury CF. Distinct genetic influences on grammar and
phonological short-term memory deficits: evidence from 6-year-old twins. Genes Brain and
Behavior 2006;5(2):158-169.
Ref ID: 5043
Abstract: Children with language impairments have limitations of phonological short-term
memory (STM) and have distinctive problems with certain aspects of grammar. Both
deficits have been proposed as phenotypic markers of heritable language impairment. We
studied 173 twin pairs, selected to be over-representative of children with risk of
developmental language impairment, using a battery of standardized language and
intelligence tests, a test of nonword repetition to index phonological STM and two elicitation
tasks to assess use of verb tense marking. As predicted, the phonological STM and the
verb tense measures both discriminated children with risk of language impairment from low
risk children, and DeFries-Fulker analysis showed that impairments on both tasks were
significantly heritable. However, there was minimal phenotypic and etiological overlap
between the two deficits, suggesting that different genes are implicated in causing these
two kinds of language difficulty. From an evolutionary perspective, these data are
consistent with the view that language is a complex function that depends on multiple
underlying skills with distinct genetic origins
632. Bishop DV, Laws G, Adams C, Norbury CF. High heritability of speech and language
impairments in 6-year-old twins demonstrated using parent and teacher report. Behav
Genet 2006;36(2):173-184.
Ref ID: 5044
Abstract: Previous twin studies have demonstrated high heritability of specific language
impairment (SLI) when the diagnosis is based on psychometric testing. The current study
measured the effectiveness of parent and teacher ratings of communication skills in
identifying heritable language impairment. The Children's Communication Checklist was
156
completed by parents and teachers of 6-year-old twins recruited from a general population
sample. One hundred and thirty twin pairs (65 MZ) were selected because at least one twin
had low language skills at 4 years of age; a further 66 pairs (37 MZ) were a low risk group
with no indication of language difficulties at 4 years. Internal consistency, inter-rater
reliability, and validity in identifying language impairment were assessed for all CCC scales.
CCC scales, especially those assessing structural language skills, were highly effective in
identifying cases of language impairment, but agreement between parent and teacher
ratings was modest. Genetic analysis revealed negligible environmental influence and
substantial genetic influence on most scales. A rater-specific effects model was fit to the
data to assess how far parents and teachers assess a common genetic factor on the CCC.
Ratings of parents and teachers were influenced to some extent by the same child
characteristics, but rater-specific effects were also evident, especially on scales measuring
pragmatic aspects of communication. This study shows that there are strong genetic
influences on both structural and pragmatic language impairments in children, and these
can be detected using a simple checklist completed by parents or teachers
633. Bishop DV, Maybery M, Wong D, Maley A, Hill W, Hallmayer J. Are phonological
processing deficits part of the broad autism phenotype? Am J Med Genet (Neuropsych Gen
) 2004;128(1):54-60.
Ref ID: 132
Abstract: Two tests of phonological processing, nonword repetition, and nonsense passage
reading, were administered to 80 probands with autistic disorder or PDDNOS (index cases)
and 59 typically developing controls, together with their parents and siblings. In addition,
parents completed a questionnaire about history of language and literacy problems, and all
participants were given tests of verbal (VIQ) and performance IQ (PIQ). Parents also
completed the Autism-Spectrum Quotient, which was used to index the broad autism
phenotype. Index probands scored well below control probands on the two phonological
tests. However, on neither phonological measure did index relatives differ from control
relatives. Within the index group, there was no relationship between the proband's level of
VIQ, or age at achieving phrase speech, and phonological score of relatives. VIQ was the
only measure to show any familiality within the index group. Reported history of language
and literacy problems did not differentiate index parents from control parents overall, but
those who were categorized as cases of the broad phenotype reported more history of
language and literacy problems than did other index parents. However, they did not have
poorer scores on the phonological measures. It is concluded that phonological processing
deficits are not part of the broad autism phenotype
634. Bishop DV, Maybery M, Maley A, Wong D, Hill W, Hallmayer J. Using self-report to identify
the broad phenotype in parents of children with autistic spectrum disorders: a study using
the Autism-Spectrum Quotient. J Child Psychol Psychiatry 2004;45(8):1431-1436.
Ref ID: 4632
Abstract: BACKGROUND: The concept of the 'broad phenotype' of autism refers to the
finding that relatives of people with autism often have mild forms of autistic-like
characteristics, such as social and communicative difficulties. This study used the Autism
Spectrum Quotient (AQ), a questionnaire devised to assess features of the broad
phenotype in adults, with parents of people with autism, to see whether they would be more
likely to obtain extreme scores than a control group. METHODS: The AQ was administered
to parents of 69 people with an autism spectrum disorder and parents of 52 controls.
RESULTS: On two of the five subscales of the AQ, social skills and communication,
parents of people with autism obtained higher scores than control parents. The other three
scales, attention to detail, attention switching, and imagination, did not differentiate groups.
The correlation between social skills and communication scales was .663. The scales can
be combined to give an index of broad phenotype. CONCLUSIONS: The AQ appears to be
sensitive to the broad phenotype, provided attention is restricted to the social skills and
communication scales
157
635. Bishop DV, Adams CV, Norbury CF. Using nonword repetition to distinguish genetic and
environmental influences on early literacy development: a study of 6-year-old twins. Am J
Med Genet (Neuropsych Gen ) 2004;129(1):94-96.
Ref ID: 4633
Abstract: This study considered whether cognitive profile could distinguish groups of
children where genes or environment played a major role in influencing reading level.
Same-sex twin pairs from an epidemiological study were categorized according to parental
report at 4 years of age into those with low language skills and a typically developing group.
A total of 132 same-sex twin pairs from the low language group and 66 from the control
group were assessed at 6 years of age, to investigate heritability of reading ability adjusted
for nonverbal IQ. For pairs where both twins had normal scores on a nonword repetition
test, heritability was zero, with environmental influences explaining all the variance. For
pairs where one or both twins had low nonword repetition, the heritability estimate was 0.79
and the variance due to shared environment was zero. Future studies of genetics of
reading development should treat those with poor nonword repetition skills as a separate
subgroup
636. Bishop DV, Clarkson B. Written language as a window into residual language deficits: a
study of children with persistent and residual speech and language impairments. Cortex
2003;39(2):215-237.
Ref ID: 4630
Abstract: Previous work has suggested that, because writing is a late-acquired and
complex skill, it may be a particularly sensitive index of language difficulties in children.
Evidence in support of this view was obtained in a study contrasting 161
normally-developing control children aged from 7.5 to 13 years with 75 twin children of the
same age who either had specific speech-language impairments, or were co-twins of
affected children. Written narratives were elicited from children using a sequence of five
photographs depicting a simple story, and were analysed for grammatical complexity and
accuracy, intelligibility, and semantic content. Only 42 of the twins could spell well enough
to attempt the narrative task. Some co-twins of affected children had deficits in written
language, despite normal performance on oral language tests. Most children with language
impairments were poor at writing, with particularly marked deficits on a measure of spelling
and punctuation. Children with language impairments made a relatively high proportion of
phonologically inaccurate spelling errors when compared with younger children at a similar
vocabulary level. Those who did poorly on a nonword repetition test were especially likely
to have poor written language. However, four children with pure speech difficulties
produced age-appropriate written narratives
637. Bishop DV. Autism and specific language impairment: categorical distinction or continuum?
Novartis Foundation Symposium 2003;251:213-226.
Ref ID: 4631
Abstract: Traditionally, autism and specific language impairment (SLI) are regarded as
distinct disorders, with differential diagnosis hinging on two features. First, in SLI one sees
isolated language impairments in the context of otherwise normal development, whereas in
autism a triad of impairments is seen, affecting communication, social interaction and
behavioural repertoire. Second, there are different communication problems in these two
conditions. Children with SLI have particular difficulty with structural aspects of language
(phonology and syntax). In contrast, abnormal use of language (pragmatics) is the most
striking feature of autism. However, recently, this conventional view has been challenged
on three counts. First, children with autism have structural language impairments similar to
those in SLI. Second, some children have symptoms intermediate between autism and
SLT. Third, there is a high rate of language impairments in relatives of people with autism,
suggesting aetiological continuities between SLI and autism. One interpretation of these
findings is to regard autism as 'SLI plus', i.e. to assume that the only factor differentiating
the disorders is the presence of additional impairments in autism. It is suggested that a
158
more plausible interpretation is to regard structural and pragmatic language impairments as
correlated but separable consequences of common underlying risk factors
638. Bishop DV. The role of genes in the etiology of specific language impairment. J Comm
Disord 2002;35(4):311-328.
Ref ID: 3883
Abstract: Although specific language impairment (SLI) often runs in families, most
pedigrees are not consistent with a single defective gene. Before progress can be made in
molecular genetics, we need a better understanding of which aspects of SLI are heritable.
Twin studies are useful in allowing us to distinguish genetic from environmental influences.
This point is illustrated with a study in which twins were given tests of nonword repetition
(regarded as an index of phonological short-term memory) and auditory processing.
Children with SLI were impaired on both measures, but these deficits had different origins.
Auditory processing problems showed no evidence of genetic influence, whereas the
nonword repetition deficit was highly heritable. Future genetic studies of SLI may be most
effective if they use measures of underlying cognitive processes, rather than relying on
conventional psychometric definitions of disorder. LEARNING OUTCOMES: Information in
this manuscript will serve to (1) equip readers with an elementary understanding of
methods used in molecular genetic studies of language impairment; (2) familiarise readers
with the logic of twin studies in behavioural genetics, using both categorical and
quantitative methods; (3) illustrate the importance of phenotype definition for genetic
research, and the usefulness of genetic methods in illuminating theoretical relationships
between deficits associated with SLI; (4) show how genetically informative methods can be
used to study environmental as well as genetic influences on impairment
639. Bishop DV. Motor immaturity and specific speech and language impairment: evidence for a
common genetic basis. Am J Med Genet 2002;114(1):56-63.
Ref ID: 4628
Abstract: Previous studies have found an association between motor immaturity and
specific language impairment in children. Data from two twin studies were used to address
the question of whether these linked deficits have a common etiology. Study 1 involved 57
MZ and 22 DZ pairs where one or both twins had specific speech/language impairment. A
control group of 173 single-born children was also tested. Motor skill was assessed using a
tapping task, which was carried out with left and right hands. Tapping scores were
converted to scaled scores adjusted for age and sex. Unaffected twins and single-born
controls did not differ in motor skill, but twins with speech and/or language impairments
obtained significantly poorer tapping scores than controls. Bivariate DeFries-Fulker analysis
pointed to shared genetic influence on tapping speed and a measure of speech production
accuracy. In study 2, 37 twin pairs from study 1 were retested 2-3 years later and combined
with 100 twin pairs from a general population sample. A timed peg-moving task was used
to assess motor skill. Children with combined speech and language impairments obtained
poorer peg-moving scores than unaffected children. Bivariate DeFries-Fulker analysis
found significant shared genetic variance for impairments on peg-moving and on a test of
nonword repetition. It is concluded that genes that put the child at risk for communicative
problems also affect motor development, with the association being most evident when
speech production is affected
640. Bishop DV, Norbury CF. Exploring the borderlands of autistic disorder and specific
language impairment: a study using standardised diagnostic instruments. J Child Psychol
Psychiatry 2002;43(7):917-929.
Ref ID: 4629
Abstract: BACKGROUND:Two studies were conducted to test claims that pragmatic
language impairment (PLI previously referred to as semantic-pragmatic disorder) is simply another term for autistic
disorder or
pervasive developmental disorder not otherwise specified (PDDNOS). Method: In Study 1,
159
21 children
aged from 6 to 9 years with language impairments were subdivided on the basis of the
Children's
Communication Checklist into 13 cases of pragmatic language impairment (PLI) and eight
cases of
typical specific language impairment (SLI-T). Parents completed the Autism Diagnostic
Interview Revised (ADI-R) and the Social Communication Questionnaire (SCQ), and the children
were given the
Autism Diagnostic Observation Schedule - Generic (ADOS-G). In Study 2, a further 11
children with
SLI-T and 18 with PLI were assessed using the SCQ and ADOS-G. In addition, six children
diagnosed
with high-functioning autism and 18 normally developing children were assessed. Results:
There was
good agreement between ADI-R and SCQ diagnoses, but poor agreement between
diagnoses based on
these parental report measures and those based on ADOS-G. In many children, symptom
profiles
changed with age. Four PLI children from Study 1 and one from Study 2 met criteria for
autistic disorder
on both parental report (ADI-R or SCQ) and ADOS-G. Many of the others showed some
autistic features,
but there was a subset of children with pragmatic difficulties who were not diagnosed as
having autism
or PDDNOS by either instrument. These children tended to use stereotyped language with
abnormal
intonation/prosody, but they appeared sociable and communicative, had normal nonverbal
communication,
and showed few abnormalities outside the language/social communication domains.
Conclusions:
Presence of pragmatic difficulties in a child with communication problems should prompt
the
clinician to evaluate autistic symptomatology, but it is dangerous to assume that all children
with
pragmatic difficulties have autism or PDDNOS.
641. Bishop DV. Genetic influences on language impairment and literacy problems in children:
same or different? Journal of Child Psychology and Psychiatry 2001;42(2):189-198.
Ref ID: 3585
Abstract: Data from two twin studies are examined to assess genetic and environmental
influences on literacy, and the etiological relationship between language and literacy. Study
1 used children from 86 families previously recruited for a study of the genetics of specific
language impairment (see Bishop, North, & Donlan, 1995), who completed tests of
single-word reading and spelling. Literacy problems in this sample were common, were
strongly heritable, and showed a close genetic relationship with poor nonword repetition.
Study 2 included two subsets of children: 37 twin pairs who had taken part in study 1, 3 to 4
years earlier, and 100 twin pairs recruited from the general population by Bishop et al.
(1999). All children were given a standardised test of nonword reading. There was no
genetic influence on nonword reading ability, either across the normal range, or at the lower
extreme, though there were significant associations with some social variables. However,
bivariate DeFries Fulker analysis suggested that in this study, as in study 1, there was
shared genetic variance between poor nonword repetition and literacy deficits. It is
concluded that poor nonword repetition, which is known to be highly heritable, puts the
child at risk for literacy problems. However, in a general population sample, such as that
included in study 2, poor nonword repetition is a relatively rare correlate of literacy
160
problems, which are more likely to have an environmental origin. Thus the different pattern
of results in the two studies can be explained if one assumes that genetic influences are
substantial only when literacy problems are severe and/or accompanied by oral language
difficulties
642. Bishop DV. Genetic and environmental risks for specific language impairment in children.
Phil Trans Royal Soc London: Series B: Biol Sci 2001;356(1407):369-380.
Ref ID: 4627
Abstract: Specific language impairment (SLI) is the term used to refer to unexplained
difficulties in language acquisition in children. Over the past decade, there has been rapid
growth of evidence indicating that genes play an important part in the aetiology of SLI.
However, further progress in elucidating the role of genes in causing SLI is limited by our
lack of understanding of the phenotype. Studies to date have been hampered by the fact
that we do not know whether SLI should be treated as a discrete disorder or a continuous
variable, let alone which measures should be used to identify cases, or how many subtypes
there are. Recent research suggests that theoretically motivated measures of underlying
processes may be better than conventional clinical diagnoses for identifying aetiologically
distinct types of language impairment. There has been a tendency for researchers to
embrace parsimony and look for a single cause of SLI-or in any event, to identify different
subtypes, each with a different single cause. Research is reviewed that suggests that may
not be a fruitful approach to SLI, and that an approach in terms of multiple risk and
protective factors, which is widely adopted in medicine, is more realistic
643. Bishop DV. How does the brain learn language? Insights from the study of children with
and without language impairment. Dev Med Child Neurol 2000;42(2):133-142.
Ref ID: 3886
Abstract: Neurobiological studies have generated new ways of thinking about development
of brain structure and function. Development involves more than just growth from simple to
complex structures. The initial over-abundance of neurons and synaptic connections is
subsequently pruned of those that are non-functional. In addition, as behavioural and
cognitive functions emerge and become automatized, the underlying brain representations
are reorganized. In this paper, I shall argue that these different modes of
neurodevelopmental change provide a useful metaphor for examining language acquisition.
It will be argued that language acquisition can involve learning to ignore and inhibit
irrelevant information, as well as forming new ways of representing complex information
economically. Modular organization is not present from the outset, but develops gradually.
This analysis suggests a new way of assessing specific language impairment (SLI). There
has been much debate as to whether children with SLI lack specific modular components of
a language processing system. I propose instead that these children persist in using
inefficient ways of representing language. Finally, I consider what we know about the
neurobiological basis of such a deficit. There is mounting evidence that children with SLI
have subtle structural anomalies affecting the language areas of the brain, which are
largely genetically determined. We should not, however, conclude that the language
difficulties are immutable
644. Bishop DV, Bishop SJ, Bright P, James C, Delaney T, Tallal P. Different origin of auditory
and phonological processing problems in children with language impairment: evidence from
a twin study. Journal of Speech, Language, & Hearing Research 1999;42(1):155-168.
Ref ID: 3038
Abstract: This study investigated the heritability of auditory processing impairment, as
assessed by Tallal's Auditory Repetition Test (ART). The sample consisted of 37 same-sex
twin pairs who had previously been selected because one or both twins met criteria for
language impairment (LI) and 104 same-sex twin pairs in the same age range (7 to 13
years) from the general population. These samples yielded 55 children who met criteria for
LI, who were compared with 76 children whose language was normal for their age (LN
group). We replicated earlier work showing that group LI is impaired relative to group LN on
161
ART. However, there was no evidence of a heritable influence on ART scores: Correlations
between twins and their co-twins were reasonably high for both MZ and DZ twins,
suggesting that performance is more influenced by shared environment than genetic
factors. Analyses of extreme scores gave a similar picture of nonsignificant group
heritability. In contrast, a test of phonological short-term memory, the Children's Nonword
Repetition Test (CNRep), gave high estimates of group heritability. In general, CNRep was
a better predictor of low language test scores than ART, but ART did make a significant
independent contribution in accounting for variance in a test of grammatical understanding
645. Bishop DV, Bishop SJ. "Twin language": a risk factor for language impairment? J Speech
Lang Hear Res 1998;41(1):150-160.
Ref ID: 4626
Abstract: Retrospective parental report of earlier "twin language" was obtained for two
groups of twins. Sample G consisted of 94 twin pairs between the ages of 7 and 13 years
recruited through the school system as a general population sample. Sample L consisted of
82 twin pairs between the ages of 7 and 13 years who had been recruited for a genetic
study; of these twin pairs at least one of the twins had a speech-language impairment
persisting to school age. Parental report of twin language was higher (around 50%) for
children with speech-language impairment than for those with normal language (11%).
Consistent with this, children with twin language obtained significantly lower mean
language scores than other children, although their mean nonverbal IQ was equivalent. The
exceptions were a handful of children whose parents described use of a "private language"
that coexisted alongside normal use of English. These findings are consistent with the view
that what is described as twin language is usually use of immature or deviant language by
two children at the same developmental level
646. Bishop DV. Pre- and perinatal hazards and family background in children with specific
language impairments: a study of twins. Brain Lang 1997;56(1):1-26.
Ref ID: 2074
647. Bishop DV. Cognitive neuropsychology and developmental disorders: uncomfortable
bedfellows. Quarterly Journal of Experimental Psychology A 1997;50(4):899-923.
Ref ID: 4624
Abstract: Cognitive neuropsychology provides a theoretical framework and methods that
can be of value in the study of developmental disorders, but the "dissociation" logic at the
centre of this approach is not well suited to the developmental context. This is illustrated
with examples from specific language impairment. Within the developing language system
there is ample evidence for interaction between levels of representation, with modularity
emerging in the course of development. This means that one typically is seeking to explain
a complex pattern of associated impairments, rather than highly selective deficits. For
instance, a selective impairment in auditory processing can have repercussions through the
language system and may lead to distinctive syntactic deficits that are seen in written as
well as spoken language. Changes in the nature of representations and in the relationships
between components of a developing system mean that cross-sectional data at a single
point in development may be misleading indicators of the primary deficit. Furthermore,
traditional cognitive neuropsychology places a disproportionate emphasis on
representational (competence) deficits, with processing (performance) deficits being
relatively neglected. Methods for distinguishing these two kinds of impairment are
discussed, as well as other approaches for elucidating the underlying nature of
developmental disorders
648. Bishop DV, North T, Donlan C. Nonword repetition as a behavioural marker for inherited
language impairment: evidence from a twin study. Journal of Child Psychology and
Psychiatry 1996;37(4):391-403.
Ref ID: 2577
Abstract: The Children's Nonword Repetition Test (CNRep) was given 39 children with
162
persistent language impairment (LI), 13 with a history of having received speech-language
therapy (resolved LI), and 79 controls, all aged from 7 to 9 years. The children with LI were
twins who had participated in a previous genetic study. Children with resolved LI, as well as
those with persistent LI, were significantly impaired on the CNRep. Comparisons of MZ and
DZ twins indicated significant heritability of a CNRep deficit. It is concluded that CNRep
provides a marker of the phenotype of heritable forms of developmental language
impairment
649. Bishop DV, North T, Donlan C. Genetic basis of specific language impairment: evidence
from a twin study. Dev Med Child Neurol 1995;37(1):56-71.
Ref ID: 2004
Abstract: Concordance rates were compared for 63 monozygotic (MZ) and 27 dizygotic
(DZ) same-sex twin pairs, aged seven years and over, selected because at least one twin
met diagnostic criteria for specific speech or language impairment. There was significant
heritability for developmental speech and language disorder, defined according to DSM-II-R
criteria. When the definition of the phenotype was broadened to include those with a past
history of disorder and those with a less pronounced discrepancy between verbal and
non-verbal ability, concordance for MZ twins was close to 100 per cent, and that for DZ
twins approximately 50 per cent. There was also close similarity between concordant twins
for type of disorder. There is good evidence that genetic factors play a role in the aetiology
of speech and language impairment; twin data may help us arrive at a clearer conception of
the phenotype as well as quantifying the extent of the genetic contribution
650. Bishop DV. Is specific language impairment a valid diagnostic category? Genetic and
psycholinguistic evidence. Phil Trans Royal Soc London: Series B: Biol Sci
1994;346(1315):105-111.
Ref ID: 2665
Abstract: Specific language impairment (SLI) is diagnosed when a child fails to develop
language normally for no apparent reason: hearing and intelligence are adequate and the
social environment is unexceptional. Definitions of SLI typically specify that the child must
have a substantial discrepancy between language ability and non-verbal IQ. However, data
from a twin study question the validity of this requirement, and indicate that SLI is not
genetically distinct from less specific disorders where language impairment occurs in the
context of low average or borderline non-verbal ability. A second question concerns the
heterogeneous language symptoms seen in SLI: do these correspond to distinct conditions,
or to different phenotypic manifestations of a common underlying disorder, or are they
merely random variations resulting from unreliable assessments? The last of these
possibilities is ruled out by the finding that twins who are concordant for language disorder
show good agreement in terms of the pattern of language impairment. However, systematic
variation in the age and ability of children in different SLI subgroups suggest that these may
correspond to variable manifestations of a core inherited language disorder, rather than
distinct diagnostic entities. [References: 29]
651. Bishop DV, Edmundson A. Language-impaired 4-year-olds: Distinguishing transient from
persistent impairment. Journal of Speech & Hearing Research 1987;52:156-170.
Ref ID: 926
652. Bishop DV, Rosenbloom L. Classification of childhood language disorders. In: Yule W,
Rutter M, editors. Language Development and Disorders. London UK: Mac Keith Press;
1987:16-41.
Ref ID: 947
653. Bishop DVM. Development of the Children's Communication Checklist (CCC): a method for
assessing qualitative aspects of communicative impairment in children. Journal of Child
Psychology & Psychiatry 1998;39(6):879-891.
Ref ID: 4625
163
Abstract: The Children's Communication Checklist (CCC) was developed to assess aspects
of communicative impairment that are not adequately evaluated by contemporary
standardised language tests. These are predominantly pragmatic abnormalities seen in
social communication, although other qualitative aspects of speech and language were
also included. Some items covering social relationships and restricted interests were
incorporated, so that the relationship between pragmatic difficulties and other
characteristics of pervasive developmental disorders could be explored. Checklist ratings
were obtained for 76 children aged 7 to 9 years, all of whom had received special
education for language impairment. In 71 cases, 2 raters (usually a teacher and
speech-language therapist) independently completed the checklist, making it possible to
establish inter-rater reliability. From an initial pool of 93 items, 70 items, grouped into 9
scales, were retained. Five of the subscales were concerned with pragmatic aspects of
communication. A composite pragmatic impairment scale formed from these subscales had
inter-rater reliability and internal consistency of around .80. This composite discriminated
between children with a school diagnosis of semantic-pragmatic disorder and those with
other types of specific language impairment (SLI). The majority of children with pragmatic
language impairments did not have any evidence of restricted interests or significant
difficulties in the domains of social relationships
654. Bishop DVM. Uncommon Understanding: Development and Disorders of Comprehension in
Children. Hove, East Sussex, UK: Psychology Press; 1997.
Ref ID: 1976
655. Bishop DVM. The underlying nature of specific language impairment. J Child Psychol
Psychiatry 1992;33(1):3-66.
Ref ID: 1622
656. Bishop DVM, Adams C. Comprehension problems in children with specific language
impairment: literal and inferential meaning. Journal of Speech & Hearing Research
1992;35(1):119-129.
Ref ID: 2649
Abstract: A group of 61 schoolchildren with specific language impairment (SLI) was
compared with a control group on a comprehension task, in which the child was questioned
about a story that had been presented either orally or as a series of pictures. Half the
questions were literal, requiring the child to provide a detail that had been mentioned or
shown explicitly in the story. The remainder required the child to make an inference about
what had not been directly shown or stated. SLI children were impaired on this task, even
after taking into account "comprehension age," as assessed on a multiple-choice test.
However, the effects of mode of presentation and question type were similar for control and
SLI groups. Children who fitted the clinical picture of semantic-pragmatic disorder had
lower scores than other SLI children on this task. In addition, they were more prone to give
answers that suggested they had not understood the question. However, as with the other
SLI children, there was no indication that they had disproportionate difficulty with inferential
questions. It is concluded that SLI children are impaired in constructing an integrated
representation from a sequence of propositions, even when such propositions are
presented nonverbally
657. Bishop DVM, Adams C. A prospective study of the relationship between specific language
impairment, phonological disorders and reading retardation. J Child Psychol Psychiatry
1990;31:1027-1050.
Ref ID: 922
658. Bishop DVM, Byers Brown B, Robson J. The relationship between phoneme discrimination,
speech production, and language comprehension in cerebral palsied individuals. J Speech
Hear Res 1990;33:210-219.
Ref ID: 1614
164
Abstract: Twenty-four individuals with impaired speech (anarthria or dysarthria) were
compared on tests of receptive language to a control group with normal speech. All
subjects were cerebral-palsied and groups were matched on age and nonverbal ability. The
speech-impaired subjects performed less well than controls on a phoneme discrimination
task in which they were required to judge whether pairs of nonwords were the same or
different. They were also impaired relative to controls on a receptive vocabulary test, but
not in understanding of grammatical structure. One year later, phoneme discrimination
skills were reassessed in this sample, using another same-different task, plus a new task in
which subjects were required to judge if the name of a picture was spoken correctly or
altered by one sound. Speech-impaired subjects performed as well as controls on the word
judgment task, indicating that they can discriminate phoneme contrasts adequately.
However, the same-different task again resulted in highly significant differences between
speech-impaired and control groups. It is concluded that poor performance on the
same-different task reflects weak memory for novel phonological strings, rather than
impaired phoneme perception. It is proposed that retention of unfamiliar words is facilitated
by overt or covert repetition, so individuals who cannot speak fluently have difficulty
remembering nonwords. This explanation can account both for the poor performance of
speech-impaired subjects on the same-different task, and for their selective deficit in
vocabulary acquisition
659. Bishop DVM, Adams C. Conversational characteristics of children with semantic- pragmatic
disorder: II. What features lead to a judgement of inappropriacy? Brit J Disord Communic
1989;24:241-263.
Ref ID: 936
660. Bishop DVM. Autism, Asperger's syndrome and semantic-pragmatic disorder: Where are
the boundaries? Brit J Disord Communic 1989;24:107-121.
Ref ID: 1719
661. Bishop DVM. Test for Reception of Grammar. 2nd ed. Manchester UK: University of
Manchester Age and cognitive Perfromance Research Centre; 1989.
Ref ID: 2989
662. Bishop DVM, Edmundson A. Is otitis media a major cause of specific developmental
language disorders? Brit J Disord Communic 1986;21:321-338.
Ref ID: 588
663. Bishop DVM. Age of onset and outcome in 'acquired aphasia with convulsive disorder'
(Landau-Kleffner syndrome). Dev Med Child Neurol 1985;27:705-712.
Ref ID: 221
664. Bishop DVM. Comprehension of English syntax by profoundly deaf children. J Child
Psychol Psychiatry 1983;24:415-434.
Ref ID: 1624
665. Bishop DVM. Comprehension of spoken, written and signed sentences in childhood
language disorders. J Child Psychol Psychiatry 1982;23:1-20.
Ref ID: 1623
Abstract: Nine children suffering from Landau-Kleffner syndrome and 25 children with
developmental expressive disorder were tested for comprehension of the grammatical
structure of English in spoken, written and signed (Paget-Gorman) language modalities. It
is shown that the comprehension problems of children with landau-Kleffner syndrome are
not restricted to spoken language, but are also found when written or signed language is
used. Further, in all three language modalities these children show deviant patterns of
comprehension consistent with the notion that they treat language as having a sequential
rather than a hierarchical structure. However, similar patterns of performance are found in
165
profoundly deaf children, indicating that peripheral auditory deprivation is a sufficient
condition for these deviant patterns of comprehension to develop
666. Bishop SL, Richler J, Lord C. Association between restricted and repetitive behaviors and
nonverbal IQ in children with autism spectrum disorders. Child Neuropsychol
2006;12(4-5):247-267.
Ref ID: 4933
Abstract: The present study explored the relationship between nonverbal IQ and restricted
and repetitive behaviors (RRBs) in 830 children with Autism Spectrum Disorders. The role
of chronological age as a moderator of this relationship was also investigated. For many
behaviors, there was a significant interaction between nonverbal IQ and chronological age,
such that nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in
older children. For the majority of such behaviors (e.g. repetitive use of objects, hand and
finger mannerisms), RRB prevalence was negatively associated with NVIQ. However, the
prevalence of certain behaviors (e.g. circumscribed interests) showed positive relationships
with NVIQ, which provides some support for the idea of different classes of RRBs. For the
severity of different RRBs, there were several significant effects for age and NVIQ, but few
interactions
667. Biswal B, Ulmer JL, Krippendorf RL et al. Abnormal cerebral activation associated with a
motor task in Tourette syndrome. AJNR: American Journal of Neuroradiology
1998;19(8):1509-1512.
Ref ID: 2363
Abstract: BACKGROUND AND PURPOSE: In Gilles de la Tourette syndrome, PET
scanning and EEG suggest an abnormal organization of the sensorimotor cortex and basal
ganglia. The purpose of this study was to use functional MR imaging to study activation in
the sensorimotor cortex in patients with Tourette syndrome. METHODS: From echo-planar
images acquired during intermittent performance of a finger-tapping task, the location of
activated pixels was determined by means of conventional signal processing methods. In
five patients with Tourette syndrome and five healthy volunteers, the number of activated
pixels in the sensorimotor cortices and supplementary motor areas were counted. The area
over which the activation was distributed was calculated. RESULTS: In the five patients,
the average number of pixels activated during the finger-tapping task in the sensorimoter
cortices and supplementary motor area (69.4 pixels) exceeded that in the volunteers (49.2
pixels). The difference was significant. The area over which the pixels was distributed was
significantly larger (25.4 vs 13.8 cm2). CONCLUSION: Motor function is organized
differently in patients with Tourette syndrome than in healthy subjects
668. Bitner-Glindzicz M. Hereditary deafness and phenotyping in humans. Br Med Bull
2002;63:73-94.
Ref ID: 4123
Abstract: Hereditary deafness has proved to be extremely heterogeneous genetically with
more than 40 genes mapped or cloned for non-syndromic dominant deafness and 30 for
autosomal recessive non-syndromic deafness. In spite of significant advances in the
understanding of the molecular basis of hearing loss, identifying the precise genetic cause
in an individual remains difficult. Consequently, it is important to exclude syndromic causes
of deafness by clinical and special investigation and to use all available phenotypic clues
for diagnosis. A clinical approach to the aetiological investigation of individuals with hearing
loss is suggested, which includes ophthalmology review, renal ultrasound scan and
neuro-imaging of petrous temporal bone. Molecular screening of the GJB2 (Connexin 26)
gene should be undertaken in all cases of non-syndromic deafness where the cause
cannot be identified, since it is a common cause of recessive hearing impairment, the
screening is straightforward, and the phenotype unremarkable. By the same token,
mitochondrial inheritance of hearing loss should be considered in all multigeneration
families, particularly if there is a history of exposure to aminoglycoside antibiotics, since
genetic testing of specific mitochondrial genes is technically feasible. Most forms of
166
non-syndromic autosomal recessive hearing impairment cause a prelingual hearing loss,
which is generally severe to profound and not associated with abnormal radiology.
Exceptions to this include DFNB2 (MYO7A), DFNB8/10 (TMPRSS3) and DFNB16 (STRC)
where age of onset may sometimes be later on in childhood, DFNB4 (SLC26A4) where
there may be dilated vestibular aqueducts and endolymphatic sacs, and DFNB9 (OTOF)
where there may also be an associated auditory neuropathy. Unusual phenotypes in
autosomal dominant forms of deafness, include low frequency hearing loss in DFNA1
(HDIA1) and DFNA6/14/38 (WFS1), mid-frequency hearing loss in DFNA8/12 (TECTA),
DFNA13 (COL11A2) and vestibular symptoms and signs in DFNA9 (COCH) and
sometimes in DFNA11 (MYO7A). Continued clinical evaluation of types and course of
hearing loss and correlation with genotype is important for the intelligent application of
molecular testing in the next few years
669. Blacher J, McIntyre LL. Syndrome specificity and behavioural disorders in young adults
with intellectual disability: cultural differences in family impact. J Intellect Disabil Res
2006;50(Pt 3):184-198.
Ref ID: 4998
Abstract: BACKGROUND: This study examined whether behaviour problems and adaptive
behaviour of low functioning young adults, and well-being of their families, varied by
diagnostic syndrome [intellectual disability (ID) only, cerebral palsy, Down syndrome,
autism], as well as by cultural group. METHODS: Behaviour disorders in young adults with
moderate to severe ID were assessed from information provided by 282 caregivers during
in-home interviews. The sample consisted of 150 Anglo participants, and 132 Latino,
primarily Spanish-speaking, participants drawn from Southern California. RESULTS:
Behaviour disorders and maternal well-being showed the same pattern across disability
syndromes. Autism was associated with the highest scores in multiple behaviour problem
areas as well as maternal reports of lower well-being. Down syndrome was associated with
the lowest behaviour problem scores and the highest maternal well-being. When behaviour
problems were controlled for, diagnostic groups accounted for no additional variance in
maternal stress or depression. The pattern of behaviour problems and well-being did not
differ by sample (Anglo vs. Latino), although level on well-being measures did. Latina
mothers reported significantly higher depression symptoms and lower morale, but also
higher positive impact from their child than did Anglo mothers. CONCLUSIONS: Caregivers
of young adults with autism report more maladaptive behaviour problems and lower
personal well-being, or stress, relative to other diagnostic groups, regardless of cultural
group. However, cultural differences exist in caregiver reports of depression, morale, and
positive perceptions. Implications for service provision aimed at families of children with
challenging behaviour problems are discussed in the context of culture
670. Black N. Glue ear: The new dyslexia. Br Med J 1985;290:1963-1965.
Ref ID: 818
671. Blackshaw AJ, Kinderman P, Hare DJ, Hatton C. Theory of mind, causal attribution and
paranoia in Asperger syndrome. Autism 2001;5(2):147-163.
Ref ID: 7202
Abstract: Theory of mind (ToM) deficits are central to autistic spectrum disorders, including
Asperger syndrome. Research in psychotic disorders has developed a cognitive model of
paranoid delusions involving abnormal causal attributions for negative events. Possible
aetiologies of these include deficits in social reasoning, specifically ToM. The present study
investigated this attributional model of paranoia in Asperger syndrome. Participants
diagnosed with Asperger syndrome scored significantly higher on a measure of paranoia
and lower on a measure of ToM, compared with the control group. They did not differ in
self-concept and causal attributions, contrary to the attributional model of paranoia. A
regression analysis highlighted private self-consciousness as the only predictor of
paranoia. The theoretical and clinical implications of these findings are discussed
167
672. Blake DT, Byl NN, Merzenich MM. Representation of the hand in the cerebral cortex.
Behav Brain Res 2002;135(1-2):179-184.
Ref ID: 4186
Abstract: In this brief review, the body of work on hand use and cortical plasticity is
reviewed. The hand movements and sensory inputs are represented in the mammalian
primary motor cortex and the anterior parietal strip. The dominant organizational rules are
that representational area is proportional to peripheral innervation, and that cortical
architecture is columnar with limited horizontal spread. The representational area and
columnar structure can be shaped by behavior and other input manipulations. The central
core systems, and especially cholinergic inputs, act as teachers of the cerebral cortex by
marking behavioral reinforcers with the release of acetylcholine. This marking is both
necessary and sufficient for plasticity to occur in sensory cortex. As a result of this temporal
marking of reinforcing events, nearly coincident inputs over restricted sensory, or motor,
segments form coherent representations in primary sensory or motor cortex. Focal dystonia
is a problem in which overuse of the hand leads to a lack of motor control, and especially
inappropriate use of sensory feedback for motor control. Receptive field size, and columnar
architecture, are highly abnormal in this disorder. The deficiencies in focal dystonia, and
their appropriate treatment, can be understood by applying the principles of cortical
plasticity to the behavioural manipulations that cause focal dystonia
673. Blakemore SJ, Tavassoli T, Calo S et al. Tactile sensitivity in Asperger syndrome. Brain
Cognit 2006;61(1):5-13.
Ref ID: 5483
Abstract: People with autism and Asperger syndrome are anecdotally said to be
hypersensitive to touch. In two experiments, we measured tactile thresholds and
suprathreshold tactile sensitivity in a group of adults with Asperger syndrome. In the first
experiment, tactile perceptual thresholds were measured. Two frequencies of vibrotactile
stimulation were used: 30 and 200 Hz. The results demonstrated significantly lower tactile
perceptual thresholds in the Asperger group at 200 Hz but not at 30 Hz, thus confirming
tactile hypersensitivity but only for one class of stimulus. A second experiment investigated
whether self-produced movement affected the perception of touch in a group of adults with
Asperger syndrome. A suprathreshold tactile stimulus was produced either by the
participant (self-produced condition) or by the experimenter (externally produced condition)
and participants were asked to rate the perception of the tactile stimulation. The results
demonstrated that, while both Asperger and control groups rated self-produced touch as
less tickly than external touch, the Asperger group rated both types of tactile stimulus as
significantly more tickly and intense than did the control group. This experiment confirms
the finding of tactile hypersensitivity, but shows that the perceptual consequences of
self-produced touch are attenuated in the normal way in people with Asperger syndrome.
An abnormality in this process cannot therefore account for their tactile hypersensitivity
674. Bland-Stewart LM, Seymour HN, Beeghly M, Frank DA. Semantic development of
African-American children prenatally exposed to cocaine. Seminars in Speech and
Language 1998;19(2):167-186.
Ref ID: 2779
Abstract: Semantic content categories were described for the single word, multiple word,
and verb relation utterances of 22 African-American 2-year-olds during a 90-min laboratory
session. Half of the toddlers had been exposed prenatally to cocaine and half were
unexposed, as documented by biological assay in the newborn period. The exposed and
unexposed groups were carefully matched on demographic, medical, and proximal
caregiving variables. Children's spontaneous utterances were transcribed from audio- and
videotapes during the laboratory session and scored for semantic features by a team of
reliable coders who were masked to child exposure status. General productive language
features (utterance length, verbosity, and intelligibility) were also assessed. To evaluate
general language and cognitive skills, the toddlers were evaluated with the Sequenced
Inventory of Communicative Development-Revised (SICD-R) and the Bayley Scales of
168
Infant Development (BSID). Although exposed and nonexposed toddlers exhibited similar
sequences of semantic development, the exposed toddlers were more restricted and
delayed in their semantic representations. No significant group differences were observed,
however, for structural features of language (e.g., utterance length, distribution of utterance
types) or for children's general language and cognitive functioning as assessed by
standardized assessments (i.e., SICD-R, BSID). Thus, a history of prenatal cocaine
exposure and associated risk factors (e.g., prenatal exposure to alcohol, diminished birth
weight) are related to delays in early semantic development. Proposed diagnostic and
treatment strategies are discussed
675. Blank M, Allen DA. Understanding 'why': its significance in early intelligence. In: Lewis M,
editor. Origins of intelligence: Infancy and early childhood. New York: Plenum Press;
1976:266-282.
Ref ID: 2821
676. Blanton RE, Levitt JG, Peterson JR et al. Gender differences in the left inferior frontal gyrus
in normal children. NeuroImage 2004;22(2):626-636.
Ref ID: 5802
Abstract: This study examined frontal lobe subregions in 46 normal children and
adolescents (25 females, mean age: 11.08, SD: 3.07; and 21 males, mean age: 10.76, SD:
2.61) to assess the effects of age and gender on volumetric measures as well as
hemispheric asymmetries. Superior, middle, inferior, and orbito-frontal gray, white, and
cerebrospinal (CSF) volumes were manually delineated in high-resolution magnetic
resonance imaging (MRI) data to assess possible morphological changes. We report a
significant age-related increase in the white matter of the left inferior frontal gyrus (IFG) in
boys (P = 0.007). Additionally, the left IFG was significantly larger in boys compared to girls
(P = 0.004). Boys showed increased gray matter volume relative to girls even after
correcting for total cerebral volume. Also, boys were found to have significant Right > Left
asymmetry patterns with greater right hemispheric volumes for total cerebral volume, total
cerebral white matter, MFG white matter, and SFG white matter (P < 0.001). Girls showed
significant Right > Left asymmetry patterns in total cerebral and SFG white matter (P <
0.001). These findings suggest continued modification of the IFG during normal
development in boys, and significant gender differences in IFG gray matter between boys
and girls that may be possibly linked to gender differences in speech development and
lateralization of language
677. Blennow E, Nielsen KB, Telenius H et al. Fifty probands with extra structurally abnormal
chromosomes characterized by fluorescence in situ hybridization. Am J Med Genet
1995;55(1):85-94.
Ref ID: 1454
678. Blesa JR, Solano A, Briones P, Prieto-Ruiz JA, Hernandez-Yago J, Coria F. Molecular
genetics of a patient with Mohr-Tranebjaerg Syndrome due to a new mutation in the DDP1
gene. Neuromolecular Med 2007;9(4):285-291.
Ref ID: 6146
Abstract: The deafness-dystonia syndrome (DDS) or Mohr-Tranebjaerg syndrome (MTS,
MIM 304700) is a rare X-linked recessive neurological disorder resulting from
loss-of-function mutations in the nuclear DDP1/TIMM8A gene, involved in the transport and
sorting of proteins to the mitochondrial inner membrane. A Mohr-Tranebjaerg patient and
his mother were subjected to clinical and molecular studies. Screening of mutations were
performed in TIMM8A, TIMM13, and other mitochondrial protein transport genes by
conformation sensitive gel electrophoresis (CSGE), followed by direct DNA sequencing of
tissue samples from the patient. Mitochondrial DNA of the patient was also sequenced at
the genes for COX subunits and some mitochondrial tRNAs. Respiratory chain activities in
a muscle biopsy and cultured fibroblasts from the patient were assessed using biochemical
methods. mRNA expression of TIMM8A and TIMM13 was determined by RT-PCR in
169
cultured fibroblasts. We identified a new case of Mohr-Tranebjaerg syndrome and report
the characteristics of a new pathogenic de novo mutation (c.112C>T, pGln38X) in the
TIMM8A gene. Biochemical measures of respiratory chain complex activities in muscle
biopsy and fibroblasts did not show a major deficiency or alteration. mRNA expression
studies demonstrated increased TIMM8A mRNA levels in cultured fibroblasts from the
patient. Phenotypic differences among published cases seem not to be related with the
mutation location or type. Our results support the idea that dysfunctions of mitochondrial
protein transport, in addition to OXPHOS deficiency, can be the basis of important
mitochondrial pathologies
679. Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of
dementia and of senile change in the cerebral gray matter of elderly subjects. Br J
Psychiatry 1968;114:797-811.
Ref ID: 1926
680. Bleuler E. Dementia praecox oder Gruppe der Schizophenien. Leipzig, Germany: Deuticke;
1911.
Ref ID: 7165
681. Bloch MH, Leckman JF, Zhu H, Peterson BS. Caudate volumes in childhood predict
symptom severity in adults with Tourette syndrome. Neurology 2005;65(8):1253-1258.
Ref ID: 4660
Abstract: BACKGROUND: Most children with Tourette syndrome (TS) experience a marked
decline in the severity of tic symptoms during adolescence. Currently no clinical measures
can predict whose tic symptoms will persist into adulthood. Previous cross-sectional
imaging studies have identified reduced caudate nucleus volumes in subjects with TS.
OBJECTIVE: To evaluate whether caudate nucleus volumes in childhood can predict the
severity of tic or obsessive-compulsive symptoms at follow-up in early adulthood.
METHODS: In a prospective longitudinal study, clinical status and basal ganglia volumes of
43 children with TS were measured on high-resolution magnetic resonance images before
age 14 years. Follow-up clinical assessments were conducted after age 16 years, an
average of 7.5 years later. Linear regression and Tobit regression analyses were used to
assess the association of basal ganglia volumes measured in childhood with the severity of
tic and obsessive-compulsive disorder (OCD) symptoms at the time of childhood MRI and
at follow-up in early adulthood. RESULTS: Volumes of the caudate nucleus correlated
significantly and inversely with the severity of tic and OCD symptoms in early adulthood.
Caudate volumes did not correlate with the severity of symptoms at the time of the MRI
scan. CONCLUSIONS: Caudate volumes in children with Tourette syndrome predict the
severity of tic and obsessive-compulsive symptoms in early adulthood. This study provides
compelling evidence that morphologic disturbances of the caudate nucleus within
cortico-striatal-thalamo-cortical circuits are central to the persistence of both tics and
obsessive-compulsive symptoms into adulthood
682. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular
mechanisms. Nat Rev Neurosci 2007;8(1):57-69.
Ref ID: 5161
Abstract: Mounting evidence indicates that microglial activation contributes to neuronal
damage in neurodegenerative diseases. Recent studies show that in response to certain
environmental toxins and endogenous proteins, microglia can enter an overactivated state
and release reactive oxygen species (ROS) that cause neurotoxicity. Pattern recognition
receptors expressed on the microglial surface seem to be one of the primary, common
pathways by which diverse toxin signals are transduced into ROS production.
Overactivated microglia can be detected using imaging techniques and therefore this
knowledge offers an opportunity not only for early diagnosis but, importantly, for the
development of targeted anti-inflammatory therapies that might slow or halt the progression
of neurodegenerative disease
170
683. Blok MJ, van den Bosch BJ, Jongen E et al. The unfolding clinical spectrum of POLG
mutations. J Med Genet 2009;46(11):776-785.
Ref ID: 6623
Abstract: BACKGROUND: Mutations in the DNA polymerase-gamma (POLG) gene are a
major cause of clinically heterogeneous mitochondrial diseases, associated with mtDNA
depletion and multiple deletions. OBJECTIVE: To determine the spectrum of POLG
mutations in our Dutch patient cohort, to evaluate the pathogenicity of novel mutations, and
to establish genotype-phenotype correlations. RESULTS: The authors identified 64
predominantly recessive mutations in 37 patients from a total of 232 patients, consisting of
23 different mutations. The substitution p.A467T was most frequently observed (n = 23),
but was as frequent in childhood cases as in adult cases. Five new pathogenic recessive
mutations, p.Lys925ArgfsX42, p.R275X, p.G426S, p.A804T and p.R869Q were identified.
The known dominant chronic progressive external ophthalmoplegia (CPEO) mutation
p.R943H was for the first time associated with premature ovarian failure as well. In 19
patients the authors identified only a single recessive mutation, or a sequence variant with
unclear clinical significance. The data substantiate earlier observations that in POLG
patients a fatal status epilepticus and liver failure can be triggered by sodium valproate. It is
therefore important to exclude POLG mutations before administering this treatment.
CONCLUSION: The clinical features of the patient are the most important features to select
putative POLG mutation carriers and not the presence of mtDNA deletions or OXPHOS
(oxidative phosphorylation) activity. The authors conclude that POLG mutations are an
important cause of heterogeneous mitochondrial pathology and that more accurate
genotype-phenotype correlations allow a more rapid genetic diagnosis and improved
prognosis for mutation carriers
684. Bloom L, Lahey M. Language Development and Language Disorders. New York: Wiley;
1978.
Ref ID: 941
685. Bloom L. Language Development: Form and Function in Emerging Grammars. Cambridge
MA: MIT Press; 1970.
Ref ID: 1226
686. Bloss CS, Courchesne E. MRI neuroanatomy in young girls with autism: a preliminary
study. J Am Acad Child Adolesc Psychiatry 2007;46(4):515-523.
Ref ID: 5107
Abstract: OBJECTIVE: To test the hypothesis that young girls and boys with autism exhibit
different profiles of neuroanatomical abnormality relative to each other and relative to
typically developing children. METHOD: Structural magnetic resonance imaging was used
to measure gray and white matter volumes (whole cerebrum, cerebral lobes, and
cerebellum) and total brain volume in nine girls (ages 2.29-5.16) and 27 boys (ages
1.96-5.33) with autism and 14 girls (ages 2.17-5.71) and 13 boys (ages 1.72-5.50) with
typical development. Structure size and the relationship between size and age were
examined. Diagnostic and cognitive outcome data were obtained after the children reached
4 to 5 years of age. RESULTS: Girls with autism exhibited nearly every size-related
abnormality exhibited by boys with autism. Furthermore, additional sites of abnormality
were observed in girls, including enlargement in temporal white and gray matter volumes
and reduction in cerebellar gray matter volume. Significant correlations were observed
between age and white matter volumes (e.g., cerebral white matter rs = 0.950) for the girls
with autism, whereas no significant age-structure size relationships were observed for the
boys with autism. CONCLUSIONS: Results suggest sex differences in etiological factors
and the biological time course of the disorder
687. Blue ME, Naidu S, Johnston MV. Altered development of glutamate and GABA receptors in
the basal ganglia of girls with Rett syndrome. Exp Neurol 1999;156(2):345-352.
Ref ID: 3520
171
Abstract: Rett syndrome (RS), a genetic disorder found almost exclusively in females, is
associated with psychomotor regression and stereotyped hand movements. To determine
whether a defect in basal ganglia amino acid neurotransmission plays a role in RS, NMDA-,
AMPA-, kainate (KA)-, and metabotropic (mGluR)-type glutamate receptors (GluRs) and
GABA receptors were labeled autoradiographically in the caudate, putamen, and globus
pallidus of postmortem brain slices from 9 RS girls and 10 age-related controls. The cases
were divided into younger (8 years or younger) and older age groups to study age-related
changes in receptor binding density. We found significant reductions in AMPA and NMDA
receptor density in the putamen and in KA receptor density in the caudate of older RS
cases compared to controls. In contrast, mGluR density in the basal ganglia of RS patients
was not altered significantly. The density of GluRs in control subjects generally showed
more limited changes with age than in RS cases. In contrast to ionotropic GluRs, GABA
receptor density was significantly increased in the caudate of young RS patients. The
effects on GluR density in the putamen, which serves a primary motor function, were
consistent with the motor deficits observed in RS, while those on amino acid transmitter
receptors in the caudate may account for some cognitive features. Our studies demonstrate
regional, receptor-subtype, and age- specific alterations in amino acid neurotransmitter
receptors in the basal ganglia of RS girls. These changes may correlate with age-related
clinical stages observed in RS
688. Blue ME, Naidu S, Johnston MV. Development of amino acid receptors in frontal cortex
from girls with Rett syndrome. Ann Neurol 1999;45(4):541-545.
Ref ID: 3522
Abstract: To determine whether a disorder of excitatory neurotransmission plays a role in
the pathophysiology of Rett syndrome (RS), N-methyl-D-aspartate (NMDA), adenosine
monophosphate acid (AMPA), kainate, and metabotropic types of glutamate receptors were
labeled autoradiographically in the superior frontal gyrus (SFG) from 9 RS patients and 10
female controls. The results showed a trend for the densities of NMDA, AMPA, gammaaminobutyric acid, and metabotropic glutamate receptors to be higher in younger patients
than in controls and for densities in older patients to fall below those of controls. The
age-related changes in SFG NMDA receptor density may be correlated with the shift from
psychomotor regression and seizures in younger stage II/III RS girls to the less epileptic
plateau stage in older girls
689. Bluestone CD. Complications and sequelae of otitis media: Workshop on effects of otitis
media on the child. Pediatrics 1983;71:639-652.
Ref ID: 819
690. Bluestone CD, et al. Workshop on the effects of otitis media on the child. Pediatrics
1983;71:639.
Ref ID: 1794
691. Bluestone CD. Otitis media in children: To treat or not to treat. N Engl J Med
1982;306:1399.
Ref ID: 769
692. Bluestone CD. Morbidity, complications and sequelae of otitis media. In: Harford ER, Bess
FH, Bluestone CD, editors. Impedance Screening for Middle Ear Disease in Children. New
York: Grune and Stratton; 1978:17-22.
Ref ID: 876
693. Bluestone CD, Beery OC, Paradise JL. Audiometry and tympanometry in relation to middle
ear effusions in children. Laryngoscope 1973;83:594-604.
Ref ID: 590
172
694. Boatman DF, Trescher WH, Smith C et al. Cortical auditory dysfunction in benign rolandic
epilepsy. Epilepsia 2008;49(6):1018-1026.
Ref ID: 5985
Abstract: PURPOSE: To evaluate cortical auditory function, including speech recognition, in
children with benign rolandic epilepsy (BRE). METHODS: Fourteen children, seven patients
with BRE and seven matched controls, underwent audiometric and behavioral testing,
simultaneous EEG recordings, and auditory-evoked potential recordings with speech and
tones. Speech recognition was tested under multiple listening conditions. RESULTS: All
participants demonstrated normal speech recognition abilities in quiet, as well as normal
peripheral and subcortical auditory function. BRE patients performed significantly worse
than controls when speech recognition was tested under adverse listening conditions,
including background noise. Five BRE patients who were impaired on two or more tests
had centrotemporal spiking on awake EEG. There were no significant group differences in
the latency or amplitude of early N100 cortical responses to speech or tones. Conversely,
the mismatch negativity, a preattentive index of cortical processing that is elicited passively,
was absent or prolonged for speech, but not tones, in BRE patients as compared to
controls. DISCUSSION: Children with BRE demonstrated specific speech recognition
impairments. Our evoked potential findings indicate that these behavioral impairments
reflect dysfunction of nonprimary auditory cortex and cannot be attributed solely to attention
difficulties. A possible association between auditory impairments and centrotemporal
spiking (>1/min) on awake EEG was identified. The pattern of speech recognition
impairments observed is a known risk factor for academic difficulties in school-age children.
Our results underscore the importance of comprehensive auditory testing, using behavioral
and electrophysiological measures, in children with BRE
695. Bobko P. Correlation and Regression: Principles amd Applications for
Industrial/Organizational Psychology and Management. New York: Mc Graw-Hill; 1995.
Ref ID: 1712
696. Bocca E, Calearo C. Central hearing processes. In: Jerger J, editor. Modern Developments
in Audiology. New York: Academic Press; 1963:337-370.
Ref ID: 565
697. Boddaert N, Chabane N, Belin P et al. Perception of complex sounds in autism: abnormal
auditory cortical processing in children. Am J Psychiatry 2004;161(11):2117-2120.
Ref ID: 4490
Abstract: OBJECTIVE: The authors have previously described less activation of left
speech-related temporal areas in adults with autism when listening to speech-like sounds
than in normal adults. Here, they investigated whether this abnormal cortical processing
was also present in children with primary autism. METHOD: Regional cerebral blood flow
was measured with positron emission tomography after premedication in 11 autistic
children and six nonautistic mentally retarded children during rest and while they were
listening to speech-like sounds. RESULTS: As with autistic adults, direct comparison
between the two groups revealed significantly less activation in the autistic group localized
in left speech-related areas. CONCLUSIONS: For the first time to their knowledge, an
activation study was performed in children with autism and has confirmed previous results
obtained in adults. The abnormal cortical auditory processing observed in both children and
adults with autism could be involved in inadequate behavioral responses to sounds and in
language impairments characteristic of autism
698. Boddaert N, Chabane N, Gervais H et al. Superior temporal sulcus anatomical
abnormalities in childhood autism: a voxel-based morphometry MRI study. NeuroImage
2004;23(1):364-369.
Ref ID: 4556
Abstract: The underlying neurobiology of autism, a severe pervasive developmental
disorder, remains unknown. Few neocortical brain MRI abnormalities have been reported.
173
Using rest functional brain imaging, two independent studies have described localized
bilateral temporal hypoperfusion in children with primary autism. In order to search for
convergent evidence of anatomical abnormalities in autistic children, we performed an
anatomical MRI study using optimized whole-brain voxel-based morphometry (VBM).
High-resolution 3-D T1-weighted MRI data sets were acquired in 21 children with primary
autism (mean age 9.3 +/- 2.2 years) and 12 healthy control children (mean age 10.8 +/- 2.7
years). By comparing autistic children to normal children, we found bilaterally significant
decreases of grey matter concentration located in superior temporal sulcus (STS) (P < 0.05
corrected, after small volume correction; SVC). Children with autism were also found to
have a decrease of white matter concentration located in the right temporal pole and in
cerebellum (P < 0.05, corrected) compared to normal children. These results suggest that
autism is associated with bilateral anatomical abnormalities localized in the STS and are
remarkably consistent with functional hypoperfusion previously reported in children with
autism. The multimodal STS areas are involved in highest level of cortical integration of
both sensory and limbic information. Moreover, the STS is now recognized as a key cortical
area of the "social brain" and is implicated in social perceptual skills that are
characteristically impaired in autism. Therefore, the convergent anatomical and functional
temporal abnormalities observed in autism may be important in the understanding of brain
behavior relationships in this severe developmental disorder
699. Boddaert N, Belin P, Chabane N et al. Perception of complex sounds: abnormal pattern of
cortical activation in autism. Am J Psychiatry 2003;160(11):2057-2060.
Ref ID: 4667
Abstract: OBJECTIVE: Bilateral temporal hypoperfusion at rest was recently described in
autism. In normal adults, these regions are activated by listening to speech-like sounds. To
investigate auditory cortical processing in autism, the authors performed a positron
emission tomography activation study. METHOD: Regional cerebral blood flow was
measured in five autistic adults and eight comparison subjects during rest and while
listening to speech-like sounds. RESULTS: Similar to the comparison subjects, autistic
patients showed a bilateral activation of the superior temporal gyrus. However, an
abnormal pattern of hemispheric activation was observed in the autistic group. The volume
of activation was larger on the right side in the autistic patients, whereas the reverse
pattern was found in the comparison group. The direct comparison between the two groups
showed that the right middle frontal gyrus exhibited significantly greater activation in the
autistic group. Conversely, the left temporal areas exhibited less activation in autistic
patients. CONCLUSIONS: These findings suggest that abnormal auditory cortical
processing is implicated in the language impairments and the inadequate response to
sounds typically seen in autism
700. Boddaert N, Zilbovicius M. Functional neuroimaging and childhood autism. Pediatr Radiol
2002;32:1-7.
Ref ID: 3593
Abstract: Childhood autism is now widely viewed as being of developmental neurobiological
origin. Yet, localised structural and functional brain correlates of autism have to be
established. Structural brain-imaging studies performed in autistic patients have reported
abnormalities such as increased total brain volume and cerebellar abnormalities. However,
none of these abnormalities fully account for the full range of autistic symptoms. Functional
brain imaging, such as positron emission tomography (PET), single photon emission
computed tomography (SPECT) and functional MRI (fMRI) have added a new perspective
to the study of normal and pathological brain functions. In autism, functional studies have
been performed at rest or during activation. However, first-generation functional imaging
devices were not sensitive enough to detect any consistent dysfunction. Recently, with
improved technology, two independent groups have reported bilateral hypoperfusion of the
temporal lobes in autistic children. In addition, activation studies, using perceptive and
cognitive paradigms, have shown an abnormal pattern of cortical activation in autistic
patients. These results suggest that different connections between particular cortical
174
regions could exist in autism. The purpose of this review is to present the main results of
rest and activation studies performed in autism
701. Bodfish JW, Parker DE, Lewis MH, Sprague RL, Newell KM. Stereotypy and motor control:
differences in the postural stability dynamics of persons with stereotyped and dyskinetic
movement disorders. Am J Ment Retard 2001;106(2):123-134.
Ref ID: 3844
Abstract: We examined whether dynamic measures of postural stability differentiated
persons with stereotyped movement disorder from persons with dyskinetic movement
disorder. Participants from three groups (stereotypy, dyskinesia, control) were given a
goal-oriented postural stability task, and performance was measured using a force platform
and computerized posturographic techniques. The results showed that both movement
disorder groups differed from the control group in the posture task. Further, the stereotypy
and dyskinesia groups demonstrated markedly different postural movement profiles. The
postural motion of the stereotypy group was characterized by greater amplitude and
variability but lower complexity than the dyskinesia group. These results provide support for
a motor control model of stereotypy
702. Bodfish JW, Symons FJ, Parker DE, Lewis MH. Varieties of repetitive behavior in autism:
comparisons to mental retardation. J Autism Dev Disord 2000;30(3):237-243.
Ref ID: 3571
Abstract: Systematic study of abnormal repetitive behaviors in autism has been lacking
despite the diagnostic significance of such behavior. The occurrence of specific
topographies of repetitive behaviors as well as their severity was assessed in individuals
with mental retardation with and without autism. The occurrence of each behavior category,
except dyskinesias, was higher in the autism group and autistic subjects exhibited a
significantly greater number of topographies of stereotypy and compulsions. Both groups
had significant patterns of repetitive behavior co-occurrence. Autistic subjects had
significantly greater severity ratings for compulsions, stereotypy, and self-injury. Repetitive
behavior severity also predicted severity of autism. Although abnormal repetition is not
specific to autism, an elevated pattern of occurrence and severity appears to characterize
the disorder
703. Bodfish JW, Newell KM, Sprague RL, Harper VN, Lewis MH. Dyskinetic movement disorder
among adults with mental retardation: phenomenology and co-occurrence with stereotypy.
Am J Ment Retard 1996;101(2):118-129.
Ref ID: 2400
Abstract: We screened for the occurrence of dyskinetic and stereotypic movement
disorders using item-independent screening protocols to determine whether these forms of
movement disorder can be distinguished among adults with mental retardation.
Stereotypies and dyskinesias were reliably distinguished in terms of topography. Tardive
dyskinesia occurred in 18.2% of a cohort of individuals receiving chronic neuroleptic
treatment. Stereotypic movement disorder was associated with increased dyskinesia
scores and increased prevalence of tardive dyskinesia. Increased dyskinesia scores were
also found for subjects exhibiting stereotypy who had been free of neuroleptic treatment for
3 years. Results indicate that dyskinesia and stereotypy are discriminable movement
disorders and provide preliminary support for the hypothesis that they may be related by
common mechanisms
704. Bodfish JW, Crawford TW, Powell SB, Parker DE, Golden RN, Lewis MH. Compulsions in
adults with mental retardation: prevalence, phenomenology, and comorbidity with
stereotypy and self-injury. Am J Ment Retard 1995;100(2):183-192.
Ref ID: 2401
Abstract: A variety of conceptual similarities between compulsions seen in individuals with
obsessive compulsive disorder and stereotypy and self-injury seen in individuals with
mental retardation led us to investigate the prevalence, phenomenology, and comorbidity of
175
compulsions in adults with severe or profound mental retardation. We developed simple
assessment screening instruments for stereotypy and self-injury and used Gedye's
Compulsive Behavior Checklist and found acceptable levels of reliability, stability, and
validity for each instrument. Prevalences were as follows: stereotypy: 60.9%; self-injury:
46.6%; and compulsion: 40%. The occurrence of compulsions was significantly positively
associated with the occurrence of stereotypy, self-injury, and stereotypy plus self-injury
705. Boel M, Casaer P. Continuous spikes and waves during slow sleep: A 30 months follow-up
study of neuropsychol ogical recovery and EEG findings. Neuropediatrics 1989;20:176-180.
Ref ID: 217
706. Boeschoten MA, Kemner C, Kenemans JL, Engeland H. The relationship between local
and global processing and the processing of high and low spatial frequencies studied by
event-related potentials and source modeling. Brain Res Cogn Brain Res
2005;24(2):228-236.
Ref ID: 4796
Abstract: The processing of global and local elements and of low- and high-spatial
frequencies are thought to be interrelated. Evidence for this stems from findings showing
that brain localizations for global/local elements and for low/high spatial frequencies seem
to overlap. The present study aimed to provide direct evidence that topographical
differences between the processing of global and local visual elements can directly be
explained by their spatial frequency content, and to study at which point in time this relation
is present. This was done by studying the event-related potentials (ERPs) and source
models elicited by unfiltered, low- or high-pass filtered hierarchical stimuli. Results showed
that performance for global and local targets was affected by removing low and high spatial
frequencies, respectively. ERP data indicated that at 250 ms, there was an interaction
between the processing of global/local targets and of spatial frequencies because at this
time-point removal of low spatial frequencies decreased activity associated with the
processing of global targets. When localizing this effect, we found evidence implying that
spatial frequency content indeed affected the brain region in which local/global targets were
processed. Results implicated that the processing of global information depended on its low
spatial frequency content, which was processed more laterally. Instead, processing of local
information seemed to depend on its high spatial frequency content, which was processed
more medially. Thereby, present results extend former results showing that global and local
processing is dependent on spatial frequency and mapped retinotopically in the visual
cortex
707. Boeve BF. Parkinson-related dementias. Neurol Clin 2007;25(3):761-81, vii.
Ref ID: 5828
Abstract: Recent advances in neurogenetics, molecular biology, and immunocytochemical
staining methods have expanded the spectrum of neurodegenerative disorders now known
to cause dementia associated with parkinsonism. This review concentrates on those rare
disorders in which cognitive impairment/dementia and parkinsonism coexist: corticobasal
syndrome/corticobasal degeneration, progressive supranuclear palsy, multiple system
atrophy, and frontotemporal dementia with parkinsonism linked to chromosome 17. The
clinical, neuropsychologic, neuroradiologic, and neuropathologic similarities and differences
in these disorders are compared and contrasted with each other and with Alzheimer's
disease, Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy
bodies, highlighting the features critical for identifying the correct diagnosis
708. Bohr V, Anson RM, Mazur S, Dianov G. Oxidative DNA damage processing and changes
with aging. Toxicol Lett 1998;102-103:47-52.
Ref ID: 3317
Abstract: Living organisms are constantly exposed to oxidative stress from environmental
agents and from endogenous metabolic processes. The resulting oxidative modifications
occur in proteins, lipids and DNA. Since proteins and lipids are readily degraded and
176
resynthesized, the most significant consequence of the oxidative stress is thought to be the
DNA modifications, which can become permanent via the formation of mutations and other
types of genomic instability. Many different DNA base changes have been seen following
some form of oxidative stress, and these lesions are widely considered as instigators for
the development of cancer and are also implicated in the process of aging. Several studies
have documented that oxidative DNA lesions accumulate with aging, and it appears that
the major site of this accumulation is mitochondrial DNA rather than nuclear DNA. The DNA
repair mechanisms involved in the removal of oxidative DNA lesions are much more
complex than previously considered. They involve base excision repair (BER) pathways
and nucleotide excision repair (NER) pathways, and there is currently a great deal of
interest in clarification of the pathways and their interactions. We have used a number of
different approaches to explore the mechanism of the repair processes, and we are able to
examine the repair of different types of lesions and to measure different steps of the repair
processes. Furthermore, we can measure the DNA damage processing in the nuclear DNA
and separately, in the mitochondrial DNA. Contrary to widely held notions, mitochondria
have efficient DNA repair of oxidative DNA damage and we are exploring the mechanisms.
In a human disorder, Cockayne syndrome (CS), characterized by premature aging, there
appear to be deficiencies in the repair of oxidative DNA damage in the nuclear DNA, and
this may be the major underlying cause of the disease
709. Bohr VA, Sander M, Kraemer KH. Rare diseases provide rare insights into nucleotide
excision repair, transcription-coupled repair, TFIIH, aging and cancer. DNA Repair
2005;4:293-302.
Ref ID: 4566
710. Bolanos CA, Glatt SJ, Jackson D. Subsensitivity to dopaminergic drugs in periadolescent
rats: a behavioral and neurochemical analysis. Brain Res 1998;Developmental Brain
Research. 111(1):25-33.
Ref ID: 2516
Abstract: It has been reported that post-natal day (PD) 30-40 rats respond differently to the
behavioral effects of dopaminergic drugs when compared to younger or older rats. In this
study, the behavioral effects of amphetamine (AMPH) on motor behavior and the effects of
dopaminergic drugs on striatal acetylcholine (ACh) release were evaluated in
periadolescent (PD35) and adult rats. AMPH increased dopamine (DA)-mediated motor
behaviors (locomotor activity and stereotypy) in periadolescent and adult rats; however,
these responses were of a lesser magnitude in periadolescent rats. In adult rats, cocaine
and nomifensine inhibited ACh overflow in a dose-dependent manner. In periadolescent
rats, ACh overflow was maximally inhibited at a lower drug concentration (5 microM) than in
adult rats (10 microM) signifying increased sensitivity in these rats. Apomorphine inhibited
ACh overflow in a dose-dependent fashion in slices from adult rats. In contrast,
apomorphine did not consistently inhibit ACh overflow in striatal slices prepared from
periadolescent rats. Collectively, the results of this study demonstrate behavioral
subsensitivity to AMPH in periadolescent rats. Examination of the effects of DA reuptake
blockers on DA modulation of striatal cholinergic neurons failed to reveal a corresponding
subsensitivity. In fact, ACh release was more sensitive to DA reuptake blockers in
periadolescent rats. This latter finding suggests that undisclosed factors override
dopaminergic modulation of striatal neurons in the mediation of behavior in periadolescent
rats. We propose that during periadolescence, DA transmission is transiently elevated. This
results in post-synaptic supersensitivity of cholinergic receptors and consequently induces
behavioral subsensitivity when challenged with dopaminergic drugs. Increased cholinergic
tone may mediate behavioral subsensitivity despite drug-induced elevations in DA.
Copyright 1998 Elsevier Science B.V
711. Boles DB, Barth JM, Merrill EC. Asymmetry and performance: toward a
neurodevelopmental theory. Brain Cognit 2008;66(2):124-139.
Ref ID: 5858
177
Abstract: Hemispheric asymmetry implies the existence of developmental influences that
affect one hemisphere more than the other. However, those influences are poorly
understood. One simple view is that asymmetry may exist because of a relationship
between a mental process' degree of lateralization and how well it functions. Data scaling
issues have largely prevented such investigations, but it is shown that scaling effects are
minimized after correction for ceiling and floor effects. After correction,
lateralization-performance correlations are pervasive. However, while some correlations
are positive, others are negative, with the direction depending on the underlying lateralized
process. Two hypotheses are proposed that can account for these relationships by pointing
either to individual differences in maturation of the corpus callosum or to developmental
limits encountered at different ages of childhood. Their investigation should contribute
toward a neurodevelopmental theory of hemispheric asymmetry
712. Boles DB. A large-sample study of sex differences in functional cerebral lateralization. J
Clin Exp Neuropsychol 2005;27(6):759-768.
Ref ID: 5859
Abstract: For practitioners, the importance of sex differences in lateralization lies in their
potential prediction of susceptibility to and recovery from hemispheric damage. However,
previous literature reviews suggest that sex accounts for only 0.1-1% of the variance in
asymmetry scores. Here a large-sample, single-laboratory approach uses tasks requiring
the recognition of bargraphs, dichotic words, facial emotions, locations, and visual words,
and visual line bisection, each sensitive to lateralization of a separate mental module. The
results agree with previous reviews, with sex accounting for a maximum of 0.9% and an
average of 0.09% of the variance, suggesting that sex has little predictive clinical utility.
However, the strength of relationship between sex and laterality depends on the nature of
the lateralized task, presumably because of differences between tasks in underlying
lateralized modules
713. Bolte S, Holtmann M, Poustka F, Scheurich A, Schmidt L. Gestalt perception and
local-global processing in high-functioning autism. J Autism Dev Disord
2007;37(8):1493-1504.
Ref ID: 5239
Abstract: This study examined gestalt perception in high-functioning autism (HFA) and its
relation to tasks indicative of local visual processing. Data on of gestalt perception, visual
illusions (VI), hierarchical letters (HL), Block Design (BD) and the Embedded Figures Test
(EFT) were collected in adult males with HFA, schizophrenia, depression and normative
controls. Individuals with HFA processed gestalt stimuli less in accord with gestalt laws,
particularly regarding the principle of similarity. Gestalt processing correlated positively with
global processing of the HL. EFT and BD performance correlated negatively with VI
susceptibility in HFA. All clinical groups succumbed less to VI than the normative sample.
Results suggest decreased gestalt perception in HFA, being associated with a more
general local visual processing bias
714. Bolte S, Poustka F. The broader cognitive phenotype of autism in parents: how specific is
the tendency for local processing and executive dysfunction? J Child Psychol Psychiatry
2006;47(6):639-645.
Ref ID: 5262
Abstract: BACKGROUND: The objective of this study was to investigate the tendency for
local processing style ('weak central coherence') and executive dysfunction in parents of
subjects with an autism spectrum disorder (ASD) compared with parents of individuals with
early onset schizophrenia (EOS) and mental retardation (MR). METHOD: Sixty-two parents
of subjects with ASD, 36 parents of subjects with EOS and 30 parents of subjects with MR
were examined. Data on two scales indicative of local visual processing (Embedded
Figures Test, Block Design) and on three executive function tests (Wisconsin Card Sorting
Test, Tower of Hanoi, Trailmaking Test) were collected for all participants. RESULTS:
Parents of subjects with ASD performed significantly faster on the Embedded Figures Test
178
compared with both control samples. No other substantial group differences were
observed. CONCLUSIONS: The findings indicate that an increased tendency for local
processing in terms of visual disembedding could be a relatively specific core feature of the
broader cognitive phenotype of autism in parents
715. Bolton P, MacDonald H, Pickles A et al. A case-control family history study of autism. J
Child Psychol Psychiatry 1994;35(5):877-900.
Ref ID: 1344
716. Bolton PF. Neuroepileptic correlates of autistic symptomatology in tuberous sclerosis.
MRDDRR 2004;10(2):126-131.
Ref ID: 4586
Abstract: Tuberous sclerosis is a genetic condition that is strongly associated with the
development of an autism spectrum disorder. However, there is marked variability in
expression, and only a subset of children with tuberous sclerosis develop autism spectrum
disorder. Clarification of the mechanisms that underlie the association and variability in
expression will potentially throw light on the biological processes involved in the etiology of
idiopathic forms of autism spectrum disorder. Current evidence indicates that the likelihood
of a child with tuberous sclerosis developing an autism spectrum disorder is greater if the
child has a mutation in the TSC2 gene, although autism can and does develop in children
with TSC1 mutations. The likelihood is also greater if the child has early-onset infantile
spasms that are difficult to control, especially if there is an epileptiform focus in the
temporal lobes. The emerging evidence is consistent with the notion that early onset
electrophysiological disturbances within the temporal lobes (and perhaps other locations)
has a deleterious effect on the development and establishment of key social cognitive
representations concerned with processing social information, perhaps especially from
faces. However, alternative mechanisms to account for the findings cannot yet be ruled out.
Future research will have to employ prospective longitudinal designs and treatment trials to
clarify the processes involved
717. Bolton PF, Pickles A, Murphy M, Rutter M. Autism, affective and other psychiatric
disorders: patterns of familial aggregation. Psychol Med 1998;28:385.
Ref ID: 2233
718. Bolton PF, Griffiths PD. Association of tuberous sclerosis of temporal lobes with autism and
atypical autism. Lancet 1997;349:392-395.
Ref ID: 1987
719. Bolton PF, Murphy M, MacDonald H, Wiart L, Pickles A, Rutter M. Obstetric complications
in autism: consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry
1997;36:272-281.
Ref ID: 2232
720. Bonati MT, Russo S, Finelli P et al. Evaluation of autism traits in Angelman syndrome: a
resource to unfold autism genes. Neurogenetics 2007;8(3):169-178.
Ref ID: 5126
Abstract: Linkage and cytogenetics studies have found the Angelman syndrome (AS)
chromosomal region to be of relevance to autism disorder (AD) or autism spectrum
disorder (ASD). Autism is considered part of the behavioural phenotype in AS based on
formal autism assessments (autism diagnostic interview-revised [ADI-R] and autism
diagnostic observation schedule [ADOS]), which have mainly addressed the deleted AS
group. We explored 23 AS patients including all genetic subtypes and made a co-morbid
diagnosis of AD/ASD in 14/23 (61%), which does not include 4 cases classified within the
broader autism spectrum disorder (bASD). Deletions accounted for the main fraction (35%),
ubiquitin-protein ligase E3A (UBE3A) mutation represented 13%, imprinting defects and
uniparental disomy 9 and 4%, respectively. UBE3A mutations due to lack of the
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homologous to the E6-associated protein carboxyl terminus domain (n = 3) were
associated with the ASD, while more distal mutations (n = 3) seem to escape from a
co-morbid diagnosis of autism/autism spectrum. Differences in severity of autistic features
were seen across subtypes of AS, with some behavioural features being unique to AS and
some representing all forms of developmental disability. Autism signs (poor/lack of eye
contact, showing, spontaneous initiation of joint attention, social quality of overtures [ADOS
algorithm items for Diagnostic and Statistical Manual of Mental Disorders-IV
(DSM-IV)/International Statistical Classification of Diseases and Related Health
Problems-10 (ICD-10) autism diagnosis belonging to the reciprocal social interaction
domain]) discriminating all the co-morbid AS categories from non-autistic AS belonged to
the social interaction domain. Impairments in the communication domain (gestures,
pointing, use of another's body, frequency of vocalisation towards others [ADOS algorithm
items for DSM-IV/ICD-10 autism diagnosis belonging to the communication domain])
justified classification of co-morbid AD/ASD vs the classification of less affected bASD.
Evaluation of the behaviour domain suggested that repetitive sensory and motor
behaviours correlate with a low developmental profile rather than being specific to autism
721. Bonaventure P, Voorn P, Luyten WH, Jurzak M, Schotte A, Leysen JE. Detailed mapping of
serotonin 5-HT1B and 5-HT1D receptor messenger RNA and ligand binding sites in
guinea-pig brain and trigeminal ganglion: clues for function. Neuroscience
1998;82(2):469-484.
Ref ID: 2497
Abstract: The similar pharmacology of the 5-HT1B and 5-HT1D receptors, and the lack of
selective compounds sufficiently distinguishing between the two receptor subtypes, have
hampered functional studies on these receptors. In order to provide clues for differential
functional roles of the two subtypes, we performed a parallel localization study throughout
the guinea-pig brain and the trigeminal ganglia by means of quantitative in situ hybridization
histochemistry (using [35S]-labelled riboprobes probes for receptor messenger RNA) and
receptor autoradiography (using a new radioligand [3H]alniditan). The anatomical patterns
of 5-HT1B and 5-HT1D receptor messenger RNA were quite different. While 5-HT1B
receptor messenger RNA was abundant throughout the brain (with highest levels in the
striatum, nucleus accumbens, olfactory tubercle, cortex, hypothalamus, hippocampal
formation, amygdala, thalamus, dorsal raphe and cerebellum), 5-HT1D receptor messenger
RNA exhibited a more restricted pattern; it was found mainly in the olfactory tubercle,
entorhinal cortex, dorsal raphe, cerebellum, mesencephalic trigeminal nucleus and in the
trigeminal ganglion. The density of 5-HT(1B/1D) binding sites (combined) obtained with
[3H]alniditan autoradiography was high in the substantia nigra, superior colliculus and
globus pallidus, whereas lower levels were detected in the caudate-putamen,
hypothalamus, hippocampal formation, amygdala, thalamus and central gray. This
distribution pattern was indistinguishable from specific 5-HT1B receptor labelling in the
presence of ketanserin under conditions to occlude 5-HT1D receptor labelling; hence the
latter were below detection level. Relationships between the regional distributions of the
receptor messenger RNAs and binding sites and particular neuroanatomical pathways are
discussed with respect to possible functional roles of the 5-HT1B and 5-HT1D receptors
722. Bond J, Roberts E, Mochida GH et al. ASPM is a major determinant of cerebral cortical
size. Nat Genet 2002;32(2):316-320.
Ref ID: 4228
Abstract: One of the most notable trends in mammalian evolution is the massive increase in
size of the cerebral cortex, especially in primates. Humans with autosomal recessive
primary microcephaly (MCPH) show a small but otherwise grossly normal cerebral cortex
associated with mild to moderate mental retardation. Genes linked to this condition offer
potential insights into the development and evolution of the cerebral cortex. Here we show
that the most common cause of MCPH is homozygous mutation of ASPM, the human
ortholog of the Drosophila melanogaster abnormal spindle gene (asp), which is essential
for normal mitotic spindle function in embryonic neuroblasts. The mouse gene Aspm is
180
expressed specifically in the primary sites of prenatal cerebral cortical neurogenesis.
Notably, the predicted ASPM proteins encode systematically larger numbers of repeated
'IQ' domains between flies, mice and humans, with the predominant difference between
Aspm and ASPM being a single large insertion coding for IQ domains. Our results and
evolutionary considerations suggest that brain size is controlled in part through modulation
of mitotic spindle activity in neuronal progenitor cells
723. Bond M, Mealing S, Anderson R et al. The effectiveness and cost-effectiveness of cochlear
implants for severe to profound deafness in children and adults: a systematic review and
economic model. Health Technol Assess 2009;13(44):1-330.
Ref ID: 7069
Abstract: OBJECTIVES: To investigate whether it is clinically effective and cost-effective to
provide (i) a unilateral cochlear implant for severely to profoundly deaf people (using or not
using hearing aids), and (ii) a bilateral cochlear implant for severely to profoundly deaf
people with a single cochlear implant (unilateral or unilateral plus hearing aid). DATA
SOURCES: Main electronic databases [MEDLINE; EMBASE; Cochrane Database of
Systematic Reviews; CENTRAL; NHS EED; DARE; HTA (NHS-CRD); EconLit; National
Research Register; and ClinicalTrials.gov] searched in October 2006, updated July 2007.
REVIEW METHODS: A systematic review of the literature was undertaken according to
standard methods. A state-transition (Markov) model of the main care pathways deaf
people might follow and the main complications and device failures was developed.
RESULTS: The clinical effectiveness review included 33 papers, of which only two were
RCTs. They used 62 different outcome measures and overall were of moderate to poor
quality. All studies in children comparing one cochlear implant with non-technological
support or an acoustic hearing aid reported gains on all outcome measures, some
demonstrating greater gain from earlier implantation. The strongest evidence for an
advantage from bilateral over unilateral implantation was for understanding speech in noisy
conditions (mean improvement 13.2%, p < 0.0001); those receiving their second implant
earlier made greater gains. Comparison of bilateral with unilateral cochlear implants plus an
acoustic hearing aid was compromised by small sample sizes and poor reporting, but
benefits were seen with bilateral implants. Cochlear implants improved children's quality of
life, and those who were implanted before attending school were more likely to do well
academically and attend mainstream education than those implanted later. In adults, there
was a greater benefit from cochlear implants than from non-technological support in terms
of speech perception. Increased age at implantation may reduce effectiveness and there is
a negative correlation between duration of deafness and effectiveness. Speech perception
measures all showed benefits for cochlear implants over acoustic hearing aids [e.g. mean
increase in score of 37 points in noisy conditions (p < 0.001) with BKB sentences];
however, prelingually deafened adults benefited less than those postlingually deafened
(mean change scores 20% versus 62%). For unilateral versus bilateral implantation,
benefits in speech perception were significant in noisy conditions on all measures [e.g. 76%
for HINT sentences (p < 0.0001)]. Quality of life measured with generic and
disease-specific instruments or by interview mostly showed significant gains or positive
trends from using cochlear implants. The Markov model base-case analysis estimated that,
for prelingually profoundly deaf children, the incremental cost-effectiveness ratio (ICER) for
unilateral implantation compared with no implantation was 13,413 pounds per
quality-adjusted life-year (QALY). Assuming the utility gain for bilateral implantation is the
same for adults and children, the ICERs for simultaneous and sequential bilateral
implantation versus unilateral implantation were 40,410 pounds and 54,098 pounds per
QALY respectively. For postlingually sensorineurally profoundly deaf adults, the
corresponding ICERs were 14,163 pounds, 49,559 pounds and 60,301 pounds per QALY
respectively. Probabilistic threshold analyses suggest that unilateral implants are highly
likely to be cost-effective for adults and children at willingness to pay thresholds of 20,000
pounds or 30,000 pounds per QALY. There are likely to be overall additional benefits from
bilateral implantation, enabling children and adults to hold conversations more easily in
social situations. CONCLUSIONS: Unilateral cochlear implantation is safe and effective for
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adults and children and likely to be cost-effective in profoundly deaf adults and profoundly
and prelingually deaf children. However, decisions on the cost-effectiveness of bilateral
cochlear implants should take into account the high degree of uncertainty within the model
regarding the probable utility gain
724. Bondy AS, Frost LA. The picture exchange communication system. Seminars in Speech
and Language 1998;19(4):373-388.
Ref ID: 3338
725. Bonn CD, Cantlon JF. The origins and structure of quantitative concepts. Cogn
Neuropsychol 2012;29(1-2):149-173.
Ref ID: 7465
Abstract: "Number" is the single most influential quantitative dimension in modern human
society. It is our preferred dimension for keeping track of almost everything, including
distance, weight, time, temperature, and value. How did "number" become psychologically
affiliated with all of these different quantitative dimensions? Humans and other animals
process a broad range of quantitative information across many psychophysical dimensions
and sensory modalities. The fact that adults can rapidly translate one dimension (e.g.,
loudness) into any other (e.g., handgrip pressure) has been long established by
psychophysics research (Stevens, 1975 ). Recent literature has attempted to account for
the development of the computational and neural mechanisms that underlie interactions
between quantitative dimensions. We review evidence that there are fundamental cognitive
and neural relations among different quantitative dimensions (number, size, time, pitch,
loudness, and brightness). Then, drawing on theoretical frameworks that explain
phenomena from cross-modal perception, we outline some possible conceptualizations for
how different quantitative dimensions could come to be related over both ontogenetic and
phylogenetic time scales
726. Bonnel A, Mottron L, Peretz I, Trudel M, Gallun E, Bonnel AM. Enhanced pitch sensitivity in
individuals with autism: a signal detection analysis. J Cogn Neurosci 2003;15(2):226-235.
Ref ID: 4743
Abstract: Past research has shown a superiority of participants with high-functioning autism
over comparison groups in memorizing picture-pitch associations and in detecting pitch
changes in melodies. A subset of individuals with autism, known as "musical savants," is
also known to possess absolute pitch. This superiority might be due to an abnormally high
sensitivity to fine-grained pitch differences in sounds. To test this hypothesis,
psychoacoustic tasks were devised so as to use a signal detection methodology.
Participants were all musically untrained and were divided into a group of 12
high-functioning individuals with autism and a group of 12 normally developing individuals.
Their task was to judge the pitch of pure tones in a "same-different" discrimination task and
in a "high-low" categorization task. In both tasks, the obtained psychometric functions
revealed higher pitch sensitivity for subjects with autism, with a more pronounced
advantage over control participants in the categorization task. These findings confirm that
pitch processing is enhanced in "high-functioning" autism. Superior performance in pitch
discrimination and categorization extends previous findings of enhanced visual
performance to the auditory domain. Thus, and as predicted by the enhanced perceptual
functioning model for peaks of ability in autism (Mottron & Burack, 2001), autistic
individuals outperform typically developing population in a variety of low-level perceptual
tasks
727. Bonvillian JD. Manual communication and autism: factors relating to sign language
acquisition. In: Siple P, Fisher SD, editors. Theoretical issues in sign language and
research. Vol 2, Psychology. Chicago,IL: University of Chicago Press; 1991.
Ref ID: 3901
182
728. Bonvillian JD, Orlansky MD, Novack LL. Developmental milestones: Sign language
acquisition and motor development. Child Dev 1983;54:1435-1445.
Ref ID: 770
729. Bonvillian JD, Nelson KE, Rhyne JM. Sign language and autism. J Autism Dev Disord
1981;11(1):125-137.
Ref ID: 2833
Abstract: Research findings and issues in teaching sign language to nonspeaking autistic
children are reviewed. Data on over 100 children indicate that nearly all autistic children
learn receptive and expressive signs, and many learn to combine signs. These children
also exhibit marked improvement in adaptive behaviors. Speech skills are acquired by
fewer children and may be developed through simultaneous speech and sign training.
Possible explanations for these results are given, together with suggestions for future
research and data collection. Recommended innovations include exposure to fluent signers
and training in discourse and code-switching. Different sign language teaching methods
need to be investigated more fully, including emphasis on training sign language within the
children's total environment and with greater staff and parental participation
730. Bonvillian JD, Nelson KE. Sign language acquisition in a mute autistic boy.
1976;41(3):339-347.
Ref ID: 2834
Abstract: A mute autistic boy learned to communicate extensively through American Sign
Language. Over a six-month period he produced many spontaneous signs and sign
combinations, and analyses of child's sign combinations indicated the presence of a full
range of semantic relations. Further evidence of conceptual progress was provided by the
child's increased score on the Peabody Picture Vocabulary Test. In addition, parents' and
teacher's reports indicated that the child's social behavior improved. The extent of the boy's
linguistic progress and associated improvement in social behavior markedly exceeds that
usually reported for mute autistic children
731. Boon-Yasidhi V, Tarugsa J, Suwanwattana C, Soising L. Risperidone in the treatment of
autistic Thai children under 4 years of age. J Med Assoc Thai 2002;85 Suppl 2:S784-S789.
Ref ID: 4498
Abstract: The authors report five cases of very young children with autistic disorder, aged
2.1-3.7 years, treated with risperidone, as part of the comprehensive intervention.
Treatment with risperidone 0.25-0.5 mg per day was associated with clinically meaningful
decreases in problem behaviors including hyperactivity, irritability, and aggressiveness.
There were also improvements in social relatedness and cooperation with developmental
treatment. All of the children tolerated the medication well and experienced no untoward
effects. The efficacy of risperidone in the treatment of very young children with autistic
disorder reported here is consistent with findings in the limited number of cases previously
reported in the literature. Controlled studies are needed to confirm the efficacy and safety
of risperidone in the treatment of these children
732. Boppana SB, Fowler KB, Vaid Y et al. Neuroradiographic findings in the newborn period
and long-term outcome in children with symptomatic congenital cytomegalovirus infection.
Pediatrics 1997;99(3):409-414.
Ref ID: 4139
Abstract: OBJECTIVE: To determine whether newborn cranial computed tomographic (CT)
scan abnormalities predict an adverse neurodevelopmental outcome in children with
symptomatic congenital cytomegalovirus (CMV) infection and to examine the association
between clinical findings at birth and imaging abnormalities. METHODS: The data from 56
children with symptomatic congenital CMV infection who underwent cranial CT scans as
newborns and were enrolled in a long-term follow-up study were analyzed. The incidence
of sequelae was compared between the groups of children with normal and abnormal
imaging studies. The relationship between CT scan results and other newborn findings was
183
also examined. RESULTS: Abnormal CT scans were noted in 70% of subjects;
intracerebral calcification was the most frequent finding. Most of the children with an
abnormal newborn CT scan (90%) developed at least one sequela, compared with 29% of
those with a normal study. Only 1 child with a normal CT scan had an IQ < 70, in contrast
to 59% of those with imaging abnormalities. In addition, almost half of the children with CT
abnormalities had an IQ < 50 compared with none of those with a normal CT scan.
Newborn CT abnormalities were also associated with an abnormal hearing screen at birth
and hearing loss on follow-up. None of the neonatal neurologic findings were predictive of
an abnormal CT scan. CONCLUSION: In neonates with symptomatic congenital CMV
infection, a cranial CT scan is a good predictor of an adverse neurodevelopmental
outcome. In addition, newborn clinical and laboratory findings did not predict
neuroradiographic abnormalities in neonates with symptomatic congenital CMV infection
733. Borden MC, Ollendick TH. An examination of the validity of social subtypes in autism. J
Autism Dev Disord 1994;24:23-37.
Ref ID: 344
734. Borg E, Samuelsson E, Dahl N. Audiometric characterization of a family with digenic
autosomal, dominant, progressive sensorineural hearing loss. Acta Otolaryngol
2000;120(1):51-57.
Ref ID: 6237
Abstract: In this study, a non-syndromic progressive bilateral high frequency hearing loss is
described in a family with 141 identified members. Recent genetic analyses indicated a
digenic inheritance with linkage to the gene loci DFNA2 and DFNA12. The affected family
members who shared haplotypes at both loci (type I) showed an early postlingual onset
and a more rapid rate of progress compared with those with one either of the two disease
associated haplotypes (type II). The audiometric pattern was cochlear without a vestibular
involvement. Auditory brainstem response audiometry and magnetic resonance imaging
indicated normal retrocochlear features. The otoacoustic emissions were affected for both
type I and type II, whereas the acoustic stapedius reflex thresholds were normal in most
cases. It is concluded that both types had an outer hair cell/micro-mechanical abnormality,
but that the DFNA 2 type might have an additional dysfunction at the level of the inner hair
cells. It is furthermore pointed out that the application of refined audiometric techniques as
well as a further development of new techniques is needed in order to characterize the
phenotypes of the rapidly expanding number of genetically defined inner ear abnormalities
735. Borgatti R, Passoni D, Dalpra L et al. Pervasive developmental disorders and inv dup(15)
syndrome. Dev Med Child Neurol 1998.
Ref ID: 2137
736. Bortolini U, Caselli MC, Leonard LB. Grammatical deficits in Italian-speaking children with
specific language impairment. J Speech Lang Hear Res 1997;40(4):809-820.
Ref ID: 2013
737. Bosco E, Mancini P, D'agosta L, Ballantyne D, Filipo R. Schooling and educational
performance in children and adolescents wearing cochlear implants. Cochlear Implants Int
2005;6(3):147-156.
Ref ID: 6433
Abstract: OBJECTIVE: The aim of the study was to assess the impact of cochlear implant
use on schooling. DESIGN: Retrospective study which examined the educational
characteristics, gap between chronological age and class attended, learning skills and
quality of social interaction with peers and adults in 50 children with cochlear implants.
METHODS: Structured interviews with parents, questionnaires for teachers, school report
cards and psychometric tests. RESULTS: Majority of children attended state schools in
mainstreamed classes; 88% had a support teacher and 86% followed Oral Communication.
These children showed a smaller disparity (0.4 years) between their chronological age and
184
class attended. No insufficient performers were seen in learning skills. Greater competence
in linguistic and logical areas tended to correspond to more intensive rehabilitation.
Children were cooperative, assertive with peers and grew fond of teachers and
communication assistants. CONCLUSIONS: Schooling proved to be satisfactory in
prelingually deafened children and adolescents wearing cochlear implants. Copyright (c)
2005 John Wiley & Sons, Ltd
738. Botting N, Conti-Ramsden G. Autism, primary pragmatic difficulties, and specific language
impairment: can we distinguish them using psycholinguistic markers? Dev Med Child
Neurol 2003;45(8):515-524.
Ref ID: 6947
Abstract: Three groups of children with communication disorders were examined using a
series of psycholinguistic markers to explore whether the tasks could identify children with
impairments other than specific language impairment (SLI), and to examine whether the
different groups within this clinical population could be distinguished reliably from one
another. The groups comprised children with autistic spectrum disorders (ASD; n = 13, all
males; mean age 10 years 10 months, range 10 years 2 months to 12 years 6 months);
children with primary pragmatic language impairment (PLI) but who did not have definite
ASD diagnoses (n = 25, 22 males, three females; mean age 11 years 3 months, range 10
years 2 months to 12 years 5 months); and children with specific language impairment
(SLI) without marked pragmatic language difficulties (n = 29, 25 males, 4 females; mean
age 10 years 10 months, range 10 years 2 months to 11 years 9 months). Clinical markers
examined were: the Children's Non-Word Repetition (CNRep), the Past Tense Task (PTT),
and the Clinical Evaluation of Language Fundamentals, Recalling Sentences. First, it was
found that the a priori groupings were not sufficiently defined and that four groups were
actually present. The PLI group was in fact two separate samples: those with PLI pure and
those with some autistic-like behaviours (referred to here as PLI plus, following Bishop
1998). Second, group comparisons indicated that CNRep was significantly lower for
children with SLI than all other groups (although this measure was not such a good
discriminator using a specificity analysis). Third, the markers were able to discriminate
between all types of communication impairment in normal control participants (n = 100; 51
females, 49 males; mean age 11 years, range 10 years 5 months to 11 years 6 months)
with sensitivity levels of at least 75% and specificity of 80%. Recalling Sentences was the
most efficient marker for all groups. Finally, analysis showed that children with PLI plus
could be accurately distinguished from all others, scoring most favourably overall on
communication markers and on performance IQ scores
739. Botting N. Semantic-pragmatic disorder (SPD) as a distinct diagnostic entity: making sense
of the boundaries. Int J Lang Commun Disord 1998;33(1):87-90.
Ref ID: 2905
740. Bottos M, Dalla BB, D'Este A, Tronick EZ. The Neurobehavioral Assessment Scale as an
instrument for early long-term prognosis and intervention in major disability in high-risk
infants. J Ped Psychol 1996;21(6):755-769.
Ref ID: 2910
Abstract: Evaluated the hypothesis that more effective prognosis is achieved by assessing
the modifiability of infants' reactions than by evaluating the presence or absence of
normal/abnormal reactions. To evaluate this hypothesis the Neurobehavioral Assessment
Scale (NAS) was developed. The NAS assesses the extent to which infants can change
their responses in functional contexts. The NAS was administered to 102 high-risk infants
repeatedly over the first 16 months of life. Analysis confirmed that the modifiability of
performance was predictive of outcome significantly earlier in development than scoring the
same items in terms of their normalcy or abnormalcy
741. Boucher J, Bigham S, Mayes A, Muskett T. Recognition and language in low functioning
autism. J Autism Dev Disord 2008;38(7):1259-1269.
185
Ref ID: 6948
Abstract: The hypothesis that a pervasive impairment of declarative memory contributes to
language impairment in low functioning autism (LFA) was tested. Participants with LFA,
high functioning autism (HFA), intellectual disability (ID) without autism, and typical
development (TD) were given two recognition tests and four tests of lexical understanding.
It was predicted that recognition would be impaired in the LFA group relative to the HFA
and TD groups but not the ID group, and that recognition would correlate with lexical
knowledge in the LFA group but none of the other groups. These predictions were
supported except that the HFA group performed more similarly to the LFA group than
expected, a finding interpreted in terms of selectively impaired episodic memory
742. Boucher J. Memory and generativity in very high functioning autism: A firsthand account,
and an interpretation. Autism 2007;11(3):255-264.
Ref ID: 5179
Abstract: JS is a highly able person with Asperger syndrome whose language and
intellectual abilities are, and always have been, superior. The first part of this short article
consists of JS's analytical account of his atypical memory abilities, and the strategies he
uses for memorizing and learning. JS has also described specific difficulties with creative
writing, which are outlined here. The second part of the article consists of an interpretation
of the problems JS describes in terms of their implications for understanding the problems
of generativity that contribute to the diagnostic impairments of imagination and creativity in
autism
743. Boucher J, Lewis V, Collis GM. Voice processing abilities in children with autism, children
with specific language impairments, and young typically developing children. J Child
Psychol Psychiatry 2000;41(7):847-857.
Ref ID: 3299
Abstract: It is well established that people with autism have impaired face processing, but
much less is known about voice processing in autism. Four experiments were therefore
carried out to assess (1) familiar voice-face and sound-object matching; (2) familiar voice
recognition; (3) unfamiliar voice discrimination; and (4) vocal affect naming and vocal-facial
affect matching. In Experiments 1 and 2 language-matched children with specific language
impairment (SLI) were the controls. In Experiments 3 and 4 language-matched children
with SLI and young mainstream children were the controls. The results were unexpected:
the children with autism were not impaired relative to controls on Experiments 1, 2 and 3,
and were superior to the children with SLI on both parts of Experiment 4, although impaired
on affect matching relative to the mainstream children. These results are interpreted in
terms of an unexpected impairment of voice processing in the children with SLI associated
partly, but not wholly, with an impairment of cross- modal processing. Performance on the
experimental tasks was not associated with verbal or nonverbal ability in either of the
clinical groups. The implications of these findings for understanding autism and SLI are
discussed
744. Boucher J. Clinical Forum: SPD as a distinct diagnostic entity: logical considerations and
directions for future research. Int J Lang Commun Disord 1998;33(1):71-81.
Ref ID: 2904
745. Boucher J. Reply: somme issues in the classification of developmental disorders. Int J Lang
Commun Disord 1998;33(1):95-108.
Ref ID: 2907
746. Boucher J. Articulation in early childhood autism. J Autism Child Schizophr
1976;6(4):297-302.
Ref ID: 5450
Abstract: Using a standardized articulation test, comparisons were made between the
articulation of autistic children and (1) a group of predominantly subnormal language
186
matched controls; (2) developmental receptive dysphasic controls. The autistic children's
articulation was significantly superior to that of both control groups. The findings are
discussed in relation to differences in the pattern of language impairment in the three
groups
747. Boudewyns A, Declau F, Smets K et al. Cytomegalovirus DNA Detection in Guthrie Cards:
Role in the Diagnostic Work-Up of Childhood Hearing Loss. Otol Neurotol 2009.
Ref ID: 6325
Abstract: INTRODUCTION:: Cytomegalovirus (CMV) infection is the leading cause of
congenital nongenetic sensorineural hearing loss (SNHL) and a major cause of prelingual
SNHL that is not present at birth. Polymerase chain reaction (PCR) analysis of dried blood
samples on the Guthrie card has been proposed as a sensitive and specific method to
screen for congenital CMV infection. METHODS:: Prospectively, consecutive infants who
failed universal neonatal hearing screening and children referred for a noncongenital SNHL
(NCHL) were included and underwent a standard audiometric and etiologic work-up. DNA
was extracted from dried blood spots on neonatal Guthrie cards and amplified by real-time
PCR. Data were available for 96 cases. RESULTS:: Mean age of the universal neonatal
hearing screening group was 3.8 +/- 2.4 months (n = 41). Auditory brain stem response
thresholds were 72.9 +/- 20.2 dB nHL. A CMV-positive PCR was obtained in 4 babies. One
test was considered false-positive. This resulted in a 7.3% prevalence of congenital CMV
infections.Mean age of the NCHL group was 4.9 +/- 3.2 years (n = 55). Hearing loss was
moderate in 37, severe in 5, and profound in 13 children. A CMV-positive PCR was
obtained in 4 children (7.3%). Other causes of SNHL were excluded in the PCR positive
cases of both study groups. CONCLUSION:: We advocate PCR for CMV DNA detection on
Guthrie cards in the etiologic work-up of childhood SNHL and recommend serologic
confirmation to exclude false-positive PCR results. 7.3% of SNHL in babies with congenital
hearing loss and children with NCHL could be attributed with this technique to congenital
CMV infection
748. Bouhlal Y, El-Euch-Fayeche G, Amouri R, Hentati F. Distinct phenotypes within autosomal
recessive ataxias not linked to already known loci. Acta Myol 2005;24(2):155-161.
Ref ID: 6283
Abstract: Autosomal recessive ataxias represent a large group of neurodegenerative
disorders characterized by progressive degeneration of central and peripheral nervous
systems and a genetic heterogeneity. To analyse clinical, neurophysiological and nerve
biopsy findings in 14 Tunisian unrelated families showing linkage exclusion to the known
autosomal recessive ataxia loci, 20 Tunisian families with a total of 73 affected subjects
were selected on the presence of a clinical phenotype associating a cerebellar ataxia with
retained tendon reflexes on at least the index patient. A genetic linkage study was
performed with markers spanning the Friedreich ataxia, Spastic ataxia of the
Charlevoix-Saguenay, Autosomal recessive ataxia associated with isolated vitamin E
deficiency, Ataxia with oculomotor apraxia, Infantile onset spinocerebellar ataxia, Ataxia
with Hearing Loss and Optic Atrophy, AT, ATLD, Spinocerebellar ataxia with axonal
neuropathy, Cayman ataxia, Cerebellar ataxia with mental retardation optic atrophy and
skin abnormalities, Salla syndrome, Marinesco-Sjogren and the Childhood Spinocerebellar
Ataxia loci. Out of the 20 families, 4 showed linkage to the spastic ataxia of the
Charlevoix-Saguenay locus, one to the Friedreich ataxia locus and one to the Ataxia with
oculomotor apraxia locus. Linkage to all tested loci has been excluded in the 14 remaining
families. These families were divided into 3 groups according to tendon reflex status in
lower limbs which appear as the most obvious distinguishing clinical sign between patients
and families: Group A was characterized by brisk tendon reflexes in lower limbs, group B
by a homogeneous feature of tendon reflexes with the absence of ankle reflexes and brisk
knee reflexes and group C by variable features of tendon reflexes in lower limbs within the
same family. Haplotype analysis and Lod score calculation did not show any evidence of
linkage to the 16 known loci of cerebellar ataxias. Aim of this study was to reveal the vast
clinical phenotypic variability in patients with autosomal recessive ataxia not linked to
187
known loci. Data obtained indicate that detailed clinical and neurophysiological nerve
investigations will be essential in order to pool patients within homogeneous subgroups for
gene mapping
749. Boulanger LM, Huh GS, Shatz CJ. Neuronal plasticity and cellular immunity: shared
molecular mechanisms. Curr Opin Neurobiol 2001;11(5):568-578.
Ref ID: 5461
Abstract: It is becoming evident that neurons express an unusual number of molecules that
were originally thought to be specific to immune functions. One such molecule, class I
major histocompatibility complex, is required in the activity-dependent refinement and
plasticity of connections in the developing and adult central nervous system, demonstrating
that molecules can perform critical roles in both systems. Recent studies reveal striking
parallels between cellular signaling mechanisms in the immune and nervous systems that
may provide unexpected insights into the development, function, and diseases of both
systems
750. Boultwood J. Ataxia telangiectasia gene mutations in leukaemia and lymphoma. J Clin
Pathol 2001;54(7):512-516.
Ref ID: 6009
Abstract: Ataxia telangiectasia (AT) is a rare multisystem, autosomal, recessive disease
characterised by neuronal degeneration, genome instability, and an increased risk of
cancer. Approximately 10% of AT homozygotes develop cancer, mostly of the lymphoid
system. Lymphoid malignancies in patients with AT are of both B cell and T cell origin, and
include Hodgkin's lymphoma, non-Hodgkin's lymphoma, and several forms of leukaemia.
The AT locus was mapped to the chromosomal region 11q22-23 using genetic linkage
analysis in the late 1980s and the causative gene was identified by positional cloning
several years later. The ATM gene encodes a large protein that belongs to a family of
kinases possessing a highly conserved C-terminal kinase domain related to the
phosphatidylinositol 3-kinase domain. Members of this kinase family have been shown to
function in DNA repair and cell cycle checkpoint control following DNA damage. Recent
studies indicate that ATM is activated primarily in response to double strand breaks and
may be considered a caretaker of the genome. Most mutations in ATM result in truncation
and destabilisation of the protein, but certain missense and splicing errors have been
shown to produce a less severe phenotype. AT heterozygotes have a slightly increased risk
of breast cancer. Atm deficient mice exhibit many of the symptoms found in patients with
AT and have a high frequency of thymic lymphoma. The association between mutation of
the ATM gene and a high incidence of lymphoid malignancy in patients with AT, together
with the development of lymphoma in Atm deficient mice, supports the proposal that
inactivation of the ATM gene may be of importance in the pathogenesis of sporadic
lymphoid malignancy. Loss of heterozygosity at 11q22-23 (the location of the ATM gene) is
a common event in lymphoid malignancy. Frequent inactivating mutations of the ATM gene
have been reported in patients with rare sporadic T cell prolymphocytic leukaemia (T-PLL),
B cell chronic lymphocytic leukaemia (B-CLL), and most recently, mantle cell lymphoma
(MCL). In contrast to the ATM mutation pattern in AT, the most frequent nucleotide
changes in these sporadic lymphoid malignancies were missense mutations. The presence
of inactivating mutations, together with the deletion of the normal copy of the ATM gene in
some patients with T-PLL, B-CLL, and MCL, establishes somatic inactivation of the ATM
gene in the pathogenesis of lymphoid malignancies, and strongly suggests that ATM
functions as a tumour suppressor. The presence of missense mutations in the germline of
patients with B-CLL has been reported, suggesting that some patients with B-CLL may be
constitutional AT heterozygotes. The putative hereditary predisposition of B-CLL, although
intriguing, warrants further investigation
751. Bourgeois BFD, Landau WM. Landau-Kleffner syndrome and temporal cortical volume
reduction: cause or effect? Neurology 2004;63(7):1152-1153.
Ref ID: 4350
188
752. Bouvard MP, Leboyer M, Launay JM et al. Low-dose naltrexone effects on plasma
chemistries and clinical symptoms in autism: A double-blind and placebo-controlled study.
Psychiat Res 1995;58(3):191-201.
Ref ID: 1678
753. Bowler DM, Brook SL. SPD and autistic spectrum disorder. Int J Lang Commun Disord
1998;33(1):91-94.
Ref ID: 2906
754. Bowman EP. Asperger syndrome: The case for a connection. Br J Psychiatry
1988;152:377-382.
Ref ID: 3
755. Boyar FZ, Whitney MM, Lossie AC et al. A family with a grand-maternally derived interstitial
duplication of proximal 15q. Clin Genet 2001;60(6):421-430.
Ref ID: 3552
Abstract: About 1% of individuals with autism or types of pervasive developmental disorder
have a duplication of the 15q11-q13 region. These abnormalities can be detected by
routine G-banded chromosome study, showing an extra marker chromosome, or
demonstrated by fluorescence in situ hybridization (FISH) analysis, revealing an interstitial
duplication. We report here the molecular, cytogenetic, clinical and neuropsychiatric
evaluations of a family in whom 3 of 4 siblings inherited an interstitial duplication of
15q11-q13. This duplication was inherited from their mother who also had a maternally
derived duplication. Affected family members had apraxia of speech, phonological
awareness deficits, developmental language disorder, dyslexia, as well as limb apraxia but
did not have any dysmorphic clinical features. The observations in this family suggest that
the phenotypic manifestations of proximal 15q duplications may also involve
language-based learning disabilities
756. Boyce WT, Frank E, Jensen PS, Kessler RC, Nelson CA, Steinberg L. Social context in
developmental psychopathology: recommendations for future research from the MacArthur
Network on Psychopathology and Development. The MacArthur Foundation Research
Network on Psychopathology and Development. [Review] [175 refs]. Dev Psychopathol
1998;10(2):143-164.
Ref ID: 2189
Abstract: Accumulating evidence suggests that social contexts in early life have important
and complex effects on childhood psychopathology. Spurred by the lack of an explicit
operational definition that could guide the study of such effects, we define a social context
operationally as "a set of interpersonal conditions, relevant to a particular behavior or
disorder and external to, but shaped and interpreted by, the individual child." Building on
this definition, we offer a series of recommendations for future research, based on five
theoretically derived propositions: (a) Contexts are nested and multidimensional; (b)
contexts broaden, differentiate, and deepen with age, becoming more specific in their
effects; (c) contexts and children are mutually determining; (d) a context's meaning to the
child determines its effects on the child and arises from the context's ability to provide for
fundamental needs; and (e) contexts should be selected for assessment in light of specific
questions or outcomes. As reflected in an increasingly rich legacy of literature on child
development and psychopathology, social contexts appear to influence emerging mental
disorders through dynamic, bidirectional interactions with individual children. Future
research will benefit from examining not only statistical interactions between child- and
context-specific factors, but also the actual transactions between children and contexts and
the transduction of contextual influences into pathways of biological mediation. Because
adverse contexts exert powerful effects on the mental health of children, it is important for
the field to generate new, more theoretically grounded research addressing the contextual
determinants of psychological well-being and disorder. [References: 175]
189
757. Boyd RD, Corley MJ. Outcome survey of early intensive behavioral intervention for young
children with autism in a community setting. Autism 2001;5(4):430-441.
Ref ID: 4301
Abstract: This article presents findings from an outcome survey of the effects of early
intensive behavioral intervention (EIBI) for young children with autism in a community
setting. Results from both individual case reviews and parent questionnaires are presented,
with the data failing to support any instances of'recovery' while still yielding a high degree of
parental satisfaction with the treatment. Moreover, a follow-up inquiry into the type of
services each child was receiving in his or her post-EIBI setting documents continued
dependence on extensive educational and related developmental services, suggesting that
the promise of future treatment sparing did not materialize. Limitations of the survey in
evaluating community-based EIBI services are discussed along with the need for further
research designed to document the effectiveness of services provided to young children
with ASD in the community
758. Boyd SG, Rivera-Gaxiola M, Towell AD, Harkness W, Neville BG. Discrimination of speech
sounds in a boy with Landau-Kleffner syndrome: an intraoperative event-related potential
study. Neuropediatrics 1996;27(4):211-215.
Ref ID: 3851
Abstract: A 7-year-old boy with severe acquired epileptic aphasia (Landau-Kleffner
syndrome) was treated by multiple subpial transections to the left temporal lobe. In the
course of electrocorticography, event-related potentials (ERP) were recorded to the
phonemes /ba/ and /ga/; /ba/ occurred 72.5% of the time and /ga/ 27.5%, in a
pseudo-random sequence. The ERPs were distributed over the middle and inferior
temporal gyri and there was a marked overlap with the area of maximal spiking detected on
the electrocorticogram. Repetition of the frequent syllable /ba/ was associated with
diminution of the prominent negative component of the ERP culminating around 550 ms
suggesting habituation. Presentation of the novel syllable /ga/ restored the amplitude of this
negative component, showing that discrimination was preserved despite the apparent
global aphasia. This finding supports clinical evidence that some children with epileptic
aphasia can still process auditory speech input. Intraoperative ERP recording may help
improve our understanding of the relationship between epileptiform activity and aspects of
language processing in Landau-Kleffner syndrome where lack of cooperation precludes
detailed clinical testing
759. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120.
Ref ID: 4512
760. Boyer J-P, Deschartrette A, Delwarde M. Autism convulsif ou syndrome de
Lennox-Gastaut? A propos de neuf observations d'autisme primaire associe au syndrome
de Lennox-Gastaut. Pediatrie 1981;36:353-368.
Ref ID: 257
761. Boylan CB, Blue ME, Hohmann CF. Modeling early cortical serotonergic deficits in autism.
Behav Brain Res 2007;176(1):94-108.
Ref ID: 5199
Abstract: Autism is a developmental brain disorder characterized by deficits in social
interaction, language and behavior. Brain imaging studies demonstrate increased cerebral
cortical volumes and micro- and macro-scopic neuroanatomic changes in children with this
disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and
behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and
these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal
models of autism have been described that replicate both etiology and pathophysiology.
We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal
mice that mimics neurochemical and structural changes in cortex and, in addition, displays
a behavioral phenotype consistent with autism. Newborn male and female mice were
190
depleted of forebrain 5-HT with injections of the serotonergic neurotoxin,
5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb).
Behavioral testing of these animals as adults revealed alterations in social, sensory and
stereotypic behaviors. Lesioned mice showed significantly increased cortical width.
Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT
containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding
to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex
of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15.
We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and
social deficits observed in both 5-HT-depleted animals and in individuals with autism, may
be the result of deficiencies in timely axonal pruning to key cerebral cortical areas
762. Boyle J, Ueda T, Oh KS et al. Persistence of repair proteins at unrepaired DNA damage
distinguishes diseases with ERCC2 (XPD) mutations: cancer-prone xeroderma
pigmentosum vs. non-cancer-prone trichothiodystrophy. Hum Mutat
2008;29(10):1194-1208.
Ref ID: 6014
Abstract: Patients with xeroderma pigmentosum (XP) have a 1,000-fold increase in
ultraviolet (UV)-induced skin cancers while trichothiodystrophy (TTD) patients, despite
mutations in the same genes, ERCC2 (XPD) or ERCC3 (XPB), are cancer-free. Unlike XP
cells, TTD cells have a nearly normal rate of removal of UV-induced 6-4 photoproducts
(6-4PP) in their DNA and low levels of the basal transcription factor, TFIIH. We examined
seven XP, TTD, and XP/TTD complex patients and identified mutations in the XPD gene.
We discovered large differences in nucleotide excision repair (NER) protein recruitment to
sites of localized UV damage in TTD cells compared to XP or normal cells. XPC protein
was rapidly localized in all cells. XPC was redistributed in TTD, and normal cells by 3 hr
postirradiation, but remained localized in XP cells at 24-hr postirradiation. In XP cells
recruitment of other NER proteins (XPB, XPD, XPG, XPA, and XPF) was also delayed and
persisted at 24 hr (p<0.001). In TTD cells with defects in the XPD, XPB, or GTF2H5 (TTDA)
genes, in contrast, recruitment of these NER proteins was reduced compared to normals at
early time points (p<0.001) and remained low at 24 hr postirradiation. These data indicate
that in XP persistence of NER proteins at sites of unrepaired DNA damage is associated
with greatly increased skin cancer risk possibly by blockage of translesion DNA synthesis.
In contrast, in TTD, low levels of unstable TFIIH proteins do not accumulate at sites of
unrepaired photoproducts and may permit normal translesion DNA synthesis without
increased skin cancer
763. Bracken P, Thomas P, Timimi S et al. Psychiatry beyond the current paradigm. Br J
Psychiatry 2012;201(6):430-434.
Ref ID: 7637
Abstract: A series of editorials in this Journal have argued that psychiatry is in the midst of
a crisis. The various solutions proposed would all involve a strengthening of psychiatry's
identity as essentially 'applied neuroscience'. Although not discounting the importance of
the brain sciences and psychopharmacology, we argue that psychiatry needs to move
beyond the dominance of the current, technological paradigm. This would be more in
keeping with the evidence about how positive outcomes are achieved and could also serve
to foster more meaningful collaboration with the growing service user movement
764. Bradford A, Dodd B. The motor planning abilities of phonologically disordered children. Eur
J Disord Communic 1994;29:349-369.
Ref ID: 1601
765. Bradford Y, Haines J, Hutcheson H et al. Incorporating language phenotypes strengthens
evidence of linkage to autism. Am J Med Genet 2001;105(6):539-547.
Ref ID: 3414
Abstract: We investigated the effect of incorporating information about proband and
191
parental structural language phenotypes into linkage analyses in the two regions for which
we found the highest signals in our first- stage affected sibling pair genome screen:
chromosomes 13q and 7q. We were particularly interested in following up on our
chromosome 7q finding in light of two prior reports of linkage of this region to
developmental language disorder, since one of the diagnostic criteria for autism is absent
or abnormal language development. We hypothesized that if the language phenotype were
genetically relevant to linkage at the chromosome 7q locus, then incorporating parents
phenotypes would increase the signal at that locus, and most of the signal would originate
from the subset of families in which both probands had severe language delay. The results
support these hypotheses. The linkage signals we obtained on chromosome 7q as well as
at least one signal on chromosome 13q are mainly attributable to the subgroup of families
in which both probands had language delay. This became apparent only when the parents'
history of language-related difficulties was also incorporated into the analyses. Although
based on our data, we were not able to distinguish between epistasis or heterogeneity
models, we tentatively concluded that there may be more than one autism susceptibility
locus related to language development. Copyright 2001 Wiley-Liss, Inc
766. Bradley EA, Summers JA, Wood HL, Bryson SE. Comparing rates of psychiatric and
behavior disorders in adolescents and young adults with severe intellectual disability with
and without autism. J Autism Dev Disord 2004;34(2):151-161.
Ref ID: 4265
Abstract: Eight males and four females with an Autism Diagnostic Interview-Revised
(ADI-R) diagnosis of autism (mean age of 16.3 years) and severe intellectual disability (IQ
< 40) were individually matched to controls on the basis of chronological age, gender, and
nonverbal IQ. The dependent measure was the Diagnostic Assessment for the Severely
Handicapped-II, which is used to screen for psychiatric and behavior disorders in
lower-functioning individuals. Participants with autism showed significantly greater
disturbances as measured by the Diagnostic Assessment for the Severely Handicapped-II
total score and seven of 13 subscales. They also averaged 5.25 clinically significant
disturbances compared with 1.25 disturbances for participants without autism. Specific
vulnerabilities to anxiety, mood, sleep, organic syndromes, and stereotypies/ tics were
found in the participants with comorbid autism
767. Bradshaw JL, Sheppard DM. The neurodevelopmental frontostriatal disorders: evolutionary
adaptiveness and anomalous lateralization. Brain Lang 2000;73(2):297-320.
Ref ID: 3927
Abstract: The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal
cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia
structures) is subject to a range of neurodevelopmental disorders: Tourette's syndrome
(TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD),
schizophrenia (SCZ), autism, and probably depression. The system is responsible for our
adaptive responses (initiation, execution, or withholding) to environmental situations, and
the above disorders, involving effectively excessive release or withholding of various types
of response, are all a consequence of changes in specific frontostriatal regions. The
disorders all have a genetic component, and their persistence in the genome indicates that
their clinical manifestations may also be associated, perhaps in low levels in close relatives,
with certain adaptive advantages in given situations. Thus autism is associated with
computational careers, depression with literary creativity, SCZ with lateral thinking and the
Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused
range of interests, and TS with competitive sports and jazz improvisation. The disorders are
all highly comorbid, and which one predominantly manifests may depend on how the
frontostriatal system happens to be compromised as a result of inherited genetic
predispositions and environmental contingency. We review the adaptive nature of the
various subclinical manifestations and the evidence for concomitant phenomena (possibly
epiphenomena): alterations in structural, functional, and behavioral lateralization in each
syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a
192
neurodevelopmental origin generally has any adaptive significance; it may often simply
serve as a marker for altered regulatory function of the frontostriatal system, alterations
which in low genetic dosage or penetrance continue to play an adaptive role in clinically
unaffected close relatives of probands, but which, in high dosage or penetrance in the
probands themselves, are generally deleterious
768. Bradsher J, Auriol J, Proietti DS et al. CSB is a component of RNA pol I transcription. Mol
Cell 2002;10(4):819-829.
Ref ID: 4446
Abstract: Mutation in the CSB gene results in the human Cockayne's syndrome (CS). Here,
we provide evidence that CSB is found not only in the nucleoplasm but also in the
nucleolus within a complex (CSB IP/150) that contains RNA pol I, TFIIH, and XPG and
promotes efficient rRNA synthesis. CSB is active in in vitro RNA pol I transcription and
restores rRNA synthesis when transfected in CSB-deficient cells. We also show that
mutations in CSB, as well as in XPB and XPD genes, all of which confer CS, disturb the
RNA pol I/TFIIH interaction within the CSB IP/150. In addition to revealing an unanticipated
function for CSB in rRNA synthesis, we show that the fragility of this complex could be one
factor contributing to the CS phenotype
769. Brambilla P, Hardan A, di Nemi SU, Perez J, Soares JC, Barale F. Brain anatomy and
development in autism: review of structural MRI studies. Brain Res Bull
2003;61(6):557-569.
Ref ID: 3911
Abstract: Autism is a neurodevelopmental disorder that severely disrupts social and
cognitive functions. MRI is the method of choice for in vivo and non-invasively investigating
human brain morphology in children and adolescents. The authors reviewed structural MRI
studies that investigated structural brain anatomy and development in autistic patients. All
original MRI research papers involving autistic patients, published from 1966 to May 2003,
were reviewed in order to elucidate brain anatomy and development of autism and rated for
completeness using a 12-item check-list. Increased total brain, parieto-temporal lobe, and
cerebellar hemisphere volumes were the most replicated abnormalities in autism.
Interestingly, recent findings suggested that the size of amygdala, hippocampus, and
corpus callosum may also be abnormal. It is conceivable that abnormalities in neural
network involving fronto-temporo-parietal cortex, limbic system, and cerebellum may
underlie the pathophysiology of autism, and that such changes could result from abnormal
brain development during early life. Nonetheless, available MRI studies were often
conflicting and could have been limited by methodological issues. Future MRI
investigations should include well-characterized groups of autistic and matched healthy
individuals, while taking into consideration confounding factors such as IQ, and
socioeconomic status
770. Brancati F, Barrano G, Silhavy JL et al. CEP290 mutations are frequently identified in the
oculo-renal form of Joubert syndrome-related disorders. Am J Hum Genet
2007;81(1):104-113.
Ref ID: 5967
Abstract: Joubert syndrome-related disorders (JSRDs) are a group of clinically and
genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the
molar tooth sign (MTS) visible on brain imaging, with variable neurological, ocular, and
renal manifestations. Mutations in the CEP290 gene were recently identified in families with
the MTS-related neurological features, many of which showed oculo-renal involvement
typical of Senior-Loken syndrome (JSRD-SLS phenotype). Here, we performed
comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of
JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients
with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of
other JSRD subtypes, with mutations identified in only two patients. The data suggest that
CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS
193
subtype. One patient with mutation displayed complete situs inversus, confirming the
clinical and genetic overlap between JSRDs and other ciliopathies
771. Brandes PJ, Ehinger DM. The effects of early middle ear pathology on auditory perception
and academic achievement. J Speech Hear Disord 1981;46:301-307.
Ref ID: 592
772. Brandt N, Kuhn S, Munkner S et al. Thyroid hormone deficiency affects postnatal spiking
activity and expression of Ca2+ and K+ channels in rodent inner hair cells. J Neurosci
2007;27(12):3174-3186.
Ref ID: 6183
Abstract: Thyroid hormone (TH) is essential for the development of hearing. Lack of TH in a
critical developmental period from embryonic day 17 to postnatal day 12 (P12) in rats and
mice leads to morphological and functional deficits in the organ of Corti and the auditory
pathway. We investigated the effects of TH on inner hair cells (IHCs) using patch-clamp
recordings, capacitance measurements, and immunocytochemistry in hypothyroid rats and
athyroid Pax8-/- mice. Spontaneous and evoked Ca2+ action potentials (APs) were present
in control IHCs from P3-P11 rats and vanished in parallel with the expression of a rapidly
activating Ca2+- and voltage-activated K+ (BK) conductance. IHCs of hypothyroid rats and
athyroid Pax8-/- mice displayed APs until the end of the third postnatal week because of
threefold elevated Ca2+ currents and missing expression of BK currents. After the fourth
postnatal week, some IHCs showed BK currents whereas adjacent IHCs did not,
demonstrated by electrophysiology and immunocytochemistry. To test whether the
prolonged spiking activity during TH deficiency may be transmitted at IHC synapses,
capacitance measurements were performed in parallel to analysis of otoferlin expression, a
protein thought to play an essential role in exocytosis of IHCs. Strikingly, otoferlin was
absent from IHCs of hypothyroid rats but not of Pax8-/- mice, although both cell types
showed exocytosis with an efficiency typical for immature IHCs. These results demonstrate
for the first time a TH-dependent control of IHC spiking activity before the onset of hearing
attributable to effects of TH on Ca2+ and BK channels. Moreover, they question an
indispensable role of otoferlin for exocytosis in IHCs
773. Brann AW. Effects of acute total and prolonged partial asphyxia on the central nervous
system of the foetal neonatal and juvenile rhesus monkey: a review. [Review] [17 refs].
Equine Veterinary Journal 1988;Supplement.(5):25-27.
Ref ID: 2428
774. Brasic JR. Movements in autistic disorder. Med Hypotheses 1999;53(1):48-49.
Ref ID: 3952
Abstract: Autistic disorder, an extremely disabling syndrome with onset in early childhood,
is associated with multiple comorbid conditions. Although autistic disorder is heterogeneous
in its manifestations, there is a subgroup of individuals with autistic disorder who display
movements that appear to be unique for the disorders. Hand flapping and a variety of
movements termed stereotypies may be pathognomonic of autistic disorder. Therefore,
identification of a movement disorder characteristic of autistic disorder may imply that the
individual has autistic disorder
775. Brasic JR, Barnett JY, Ahn SC, Nadrich RH, Will MV, Clair A. Clinical assessment of
self-injurious behavior. Psychol Rep 1997;80(1):155-160.
Ref ID: 29
Abstract: The Timed Self-injurious Behavior Scale is an observational scale rating the
frequency of 16 types of self-injurious behaviors during each 10-sec. interval of a 10-min.
observation period. Advantages of the scale are utilization of direct observation and
independence from the variable recollection of symptoms by subjects and care givers. 19
videotaped sessions of a subject who exhibited eight types of self-injurious behaviors were
rated with the scale independently by three raters. Eighty percent and better agreement
194
was found for the four specific forms of those behaviors exhibited by the subject sufficiently
frequently, self biting, head punching, head slapping, and hair removal
776. Brauer J, Anwander A, Friederici AD. Neuroanatomical prerequisites for language functions
in the maturing brain. Cereb Cortex 2011;21(2):459-466.
Ref ID: 7780
Abstract: The 2 major language-relevant cortical regions in the human brain, Broca's area
and Wernicke's area, are connected via the fibers of the arcuate fasciculus/superior
longitudinal fasciculus (AF/SLF). Here, we compared this pathway in adults and children
and its relation to language processing during development. Comparison of fiber properties
demonstrated lower anisotropy in children's AF/SLF, arguing for an immature status of this
particular pathway with conceivably a lower degree of myelination. Combined diffusion
tensor imaging (DTI) data and functional magnetic resonance imaging (fMRI) data indicated
that in adults the termination of the AF/SLF fiber projection is compatible with functional
activation in Broca's area, that is pars opercularis. In children, activation in Broca's area
extended from the pars opercularis into the pars triangularis revealing an alternative
connection to the temporal lobe (Wernicke's area) via the ventrally projecting extreme
capsule fiber system. fMRI and DTI data converge to indicate that adults make use of a
more confined language network than children based on ongoing maturation of the
structural network. Our data suggest relations between language development and brain
maturation and, moreover, indicate the brain's plasticity to adjust its function to available
structural prerequisites
777. Braverman I, Jaber L, Levi H et al. Audiovestibular findings in patients with deafness
caused by a mitochondrial suceptibility mutation and precipitated by an inherited nuclear
mutation or aminoglycosides. Arch Otolaryng 1996;122(9):1001-1004.
Ref ID: 1766
778. Braverman M, Fein D, Lucci D, Waterhouse L. Affect comprehension in children with
pervasive developmental disorders. J Autism Dev Disord 1989;19:301-316.
Ref ID: 402
779. Breau LM, Camfield CS, Symons FJ et al. Relation between pain and self-injurious
behavior in nonverbal children with severe cognitive impairments. J Pediatr
2003;142(5):498-503.
Ref ID: 4814
Abstract: OBJECTIVES: To explore whether self-injurious behavior (SIB) alters pain
expression in children with severe cognitive impairments and the relation between SIB and
chronic pain. STUDY DESIGN: Caregivers of 101 nonverbal children 3 to 18 years of age
(55% boys) completed the Non-Communicating Children's Pain Checklist-Revised
(NCCPC-R) retrospectively and for an observed pain episode. Caregivers of children with
SIB (n = 44) completed the Behavior Problems Inventory, the Self-Injury Grid, and the
Self-Injury and Self-Restraint Checklist. RESULTS: Multivariate analysis of variance
indicated that NCCPC-R scores did not differ between children with and those without SIB.
However, t tests indicated that children with chronic pain (n = 13) self-injured less body
surface (P =.01) and fewer body sites (P =.04) than did children without (n = 31). Multiple
Correspondence Analysis generated 2 dimensions (49% variance), suggesting a distinction
between two SIB forms: (1) high frequency of SIB to the head/hand and absence of chronic
pain and (2) less frequent SIB near the site of pain. CONCLUSIONS: Children with severe
cognitive impairments who display SIB do not have reduced pain expression, and chronic
pain may influence the frequency and location of SIB. Further research should examine the
usefulness of these findings for management of SIB and pain
780. Breese CR, Adams C, Logel J et al. Comparison of the regional expression of nicotinic
acetylcholine receptor alpha7 mRNA and [125I]-alpha-bungarotoxin binding in human
postmortem brain. J Comp Neurol 1997;387(3):385-398.
195
Ref ID: 2290
Abstract: Neuronal nicotinic acetylcholine receptors are expressed in the human central
nervous system. A specific subtype of this receptor family, the alpha7 nicotinic
acetylcholine receptor, is thought to be the principal alpha-bungarotoxin
(alphaBTX)-binding protein in mammalian brain. Although the expression of this receptor
subtype has been characterized in rat, no study has specifically compared the expression
of both the alpha7 gene and the localization of BTX binding sites in human brain.
Expression of alpha7 mRNA and receptor protein in human postmortem brain tissue was
examined by in situ hybridization and [125I]-alpha-bungarotoxin autoradiography,
respectively, with particular emphasis on regions associated with sensory processing.
Regions with high levels of both alpha7 gene expression and [125I]-alphaBTX binding
include the nucleus reticularis of the thalamus, the lateral and medial geniculate bodies, the
basilar pontine nucleus, the horizontal limb of the diagonal band of Broca, the nucleus
basalis of Meynert, and the inferior olivary nucleus. High-to-moderate levels of alpha7
probe hybridization were also seen in the hippocampus and the cerebral cortex; however,
there was a reduced or variable degree of [125I]-alphaBTX binding in these regions
compared with the level of probe hybridization. In most brain regions, [125I]-alphaBTX
binding was localized to neuronal cell bodies similar in morphology to those that exhibited
alpha7 hybridization, suggesting that the high-affinity [125I]-alphaBTX binding sites in the
human brain are likely to be principally composed of alpha7 receptor subtypes
781. Bregman JD, Gerdtz J. Behavioral interventions. In: Cohen DJ, Volkmar FR, editors.
Handbook of autism and pervasive developmental disorders. 2 ed. New York: John Wiley &
Sons; 1997:606-630.
Ref ID: 2900
782. Breiter HC, Rauch SL, Kwong KK et al. Functional magnetic resonance imaging of
symptom provocation in obsessive-compulsive disorder. Arch Gen Psychiat
1996;53(7):595-606.
Ref ID: 2504
Abstract: BACKGROUND: The new technique of functional magnetic resonance imaging
was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder
symptoms. METHODS: Ten patients with obsessive-compulsive disorder and 5 normal
subjects were studied via functional magnetic resonance imaging during control and
provoked conditions. Data analysis entailed parametric and nonparametric statistical
mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3)) showed activation for
70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral
frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate,
lenticulate, and amygdala. No normal subjects exhibited activation in any brain region.
CONCLUSIONS: Results of functional magnetic resonance imaging were consistent with
past studies of obsessive-compulsive disorder that used other functional neuroimaging
modalities. However, paralimbic and limbic activations were more prominent in the present
study
783. Breiter HC, Rauch SL. Functional MRI and the study of OCD: from symptom provocation to
cognitive-behavioral probes of cortico-striatal systems and the amygdala. [Review] [100
refs]. NeuroImage 1996;4(3 Pt 3):S127-S138.
Ref ID: 2508
Abstract: Functional magnetic resonance imaging (fMRI) first appeared in 1991. Since that
time there has been a burgeoning use of the technology by psychiatric researchers and
neuroscientists. Our group first used fMRI to study obessive compulsive disorder (OCD)
with a symptom provocation paradigm and then moved to the use of circuitry-specific
cognitive-behavioral probes. The techniques we utilized for the symptom provocation study
remain valid today, but have been supplemented by a wide array of new tools. Functional
MRI continues to be a rapidly developing technology which could become the gold
standard for neuroimaging research in psychiatry. With this in mind, this paper focuses on
196
the past, present, and future applications of fMRI to one model illness, namely OCD. We
examine the strengths and limitations of our initial OCD symptom provocation study and
then evaluate the use of fMRI with cognitive-behavioral probes of cortico-striatal circuitry
and limbic (amygdala) circuitry. We conclude with a brief summary of foreseeable
developments which will influence the implementation of fMRI for psychiatric neuroscience
in general. [References: 100]
784. Bremer A, Giacobini M, Nordenskjold M et al. Screening for copy number alterations in loci
associated with autism spectrum disorders by two-color multiplex ligation-dependent probe
amplification. Am J Med Genet B Neuropsychiatr Genet 2010;153B(1):280-285.
Ref ID: 6522
Abstract: The autism spectrum disorder (ASD) is a heterogenous condition characterized
by impaired socialization and communication in association with stereotypic behaviors.
ASD is highly heritable and heterogeneous with a complex genetic etiology. Recurrent
submicroscopic deletions or duplications have been identified in a subgroup of individuals
with ASD using array technology. Adequate genetic testing for these genomic imbalances
have not yet been widely implemented in the diagnostic setting due to lack of feasible and
cost-effective methods as well as difficulties to interpret the clinical significance of these
small copy number variants (CNVs). We developed a multiplex ligation-dependent probe
amplification (MLPA) assay to investigate its usefulness for detection of copy number
alterations (CNAs) in autistic patients. This test proved to be easy to perform, fast,
cost-effective, and suitable for reliable detection of multiple loci in a single reaction. We
screened 148 autistic patients for 15 different loci covering 26 genes and found a 15q11-13
interstitial duplication that had escaped detection by conventional karyotyping in 1.3% of
the patients. Synthetic probe MLPA allows for a flexible analysis of a continuously
increasing number of CNAs associated with autism. Our result show that MLPA assay is an
easy and cost-effective method for the identification of selected CNAs in diagnostic
laboratories
785. Bremner MH. Visual acuity in the primary school child aged four to twelve years: a review
of amblyopia treatment in this age group at Princess Margaret Hospital. Australian Journal
of Ophthalmology 1984;12(4):395-399.
Ref ID: 2758
Abstract: A survey of the incidence in Western Australia of amblyopia assessed through the
school vision screening programme and Princess Margaret Hospital (PMH) eye clinics
shows the figure to be 0.12%, being new cases detected in primary school children each
year. Occlusion methods of treatment for amblyopia acceptable in the younger age-group
are much less tolerated by both parents and child in the school-age group. The PMH series
involving 240 children between the ages of four and 12 years showed that an amblyopic
eye with macula or paramacula fixation can be successfully treated up to the age of 10
years without constant occlusion. Also, eccentric fixation can be cured up to the 7th
birthday, but no alternative has been found for the mandatory constant occlusion. Medical,
developmental and behavioural problems can influence the management and response in
the four to twelve-year-old child; if these are not recognized and the child treated as a
whole during the critical stages of natural development of the visual system, these children
can be left with an unnecessary visual disadvantage for the next 70 years of their life
786. Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A.
Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander
disease. Nat Genet 2001;27(1):117-120.
Ref ID: 6787
Abstract: Alexander disease is a rare disorder of the central nervous system of unknown
etiology. Infants with Alexander disease develop a leukoencephalopathy with
macrocephaly, seizures and psychomotor retardation, leading to death usually within the
first decade; patients with juvenile or adult forms typically experience ataxia, bulbar signs
and spasticity, and a more slowly progressive course. The pathological hallmark of all
197
forms of Alexander disease is the presence of Rosenthal fibers, cytoplasmic inclusions in
astrocytes that contain the intermediate filament protein GFAP in association with small
heat-shock proteins. We previously found that overexpression of human GFAP in
astrocytes of transgenic mice is fatal and accompanied by the presence of inclusion bodies
indistinguishable from human Rosenthal fibers. These results suggested that a primary
alteration in GFAP may be responsible for Alexander disease. Sequence analysis of DNA
samples from patients representing different Alexander disease phenotypes revealed that
most cases are associated with non-conservative mutations in the coding region of GFAP.
Alexander disease therefore represents the first example of a primary genetic disorder of
astrocytes, one of the major cell types in the vertebrate CNS
787. Brett PM, Curtis D, Robertson MM, Gurling HM. Neuroreceptor subunit genes and the
genetic susceptibility to Gilles de la Tourette syndrome. Biological Psychiatry
1997;42(10):941-947.
Ref ID: 2389
Abstract: Segregation studies have shown that Gilles de la Tourette Syndrome (GTS) is
probably transmitted as an autosomal dominant gene disorder and can therefore be studied
by classical linkage analysis to identify susceptibility loci. Many neurotransmitter systems
have been implicated in the etiology of GTS. Most recently the alpha-1 subunit of the
glycine receptor etiologically responsible for hyperekplexia has been hypothesized as the
cause of the susceptibility to GTS. Because of this and the high concentration of other
neuroreceptor genes at 5q33-35, it was decided to study this region and the associated
gene cluster on chromosome 4p12-16 in a large British kindred multiply affected with GTS
and chronic motor tics. The genotypes of the microsatellite markers at these loci were
determined by polymerase chain reaction. The allele data were analyzed using both
parametric and nonparametric methods. Approximate multipoint maps were constructed
across the regions of interest using FASTLINK. All of the lod scores produced were
negative, showing no evidence of linkage to GTS in the family studied. The multipoint maps
showed good exclusion across these regions. The glycine receptor gene responsible for
hyperekplexia and the other neuroreceptor genes examined in this paper are not involved
in the etiology of GTS in this large pedigree
788. Brimacombe M, Ming X, Lamendola M. Prenatal and birth complications in autism. Matern
Child Health J 2007;11(1):73-79.
Ref ID: 5278
Abstract: OBJECTIVES: Prenatal and birth history as potential sources of risk factors in
relation to the onset of autism were examined. METHODS: A cohort of 164 families of
autistic children referred to The Autism Center at New Jersey Medical School-UMDNJ,
Newark, New Jersey, over a two-year period was studied. Intake prenatal and birth history
information was obtained from each family and reviewed by a clinician. RESULTS:
Prevalence rates in this cohort for vaginal bleeding, prolonged labor and prematurity were
higher than comparable rates reported nationally and in New Jersey. Clustering of multiple
prenatal risk factors was observed. This clustering was associated with the age of the
mother, but uncorrelated with birth order. CONCLUSIONS: These findings support the
general hypothesis that systemic problems at the prenatal stage may form a distinct
dimension of risk associated with autism
789. Brimacombe MB, Pickett R, Pickett J. Autism post-mortem neuroinformatic resource: the
autism tissue program (ATP) informatics portal. J Autism Dev Disord 2007;37(3):574-579.
Ref ID: 6721
Abstract: The Autism Tissue Program (ATP) was established to oversee and manage brain
donations related to neurological research in autism. The ATP Informatics Portal
(www.atpportal.org) is an integrated data access system based on Oracle technology,
developed to provide access for researchers to information on this rare tissue resource. It
also permits sorting of existing cases based on donor ante-mortem history as well as
agonal states and post-mortem tissue conditions. Phase II of development established
198
administrative tracking of registrants intending to donate, as well as management of tissue
requests and the awarding and tracking of tissue. Phase III is the ongoing assimilation of
data sets derived from research on a core group of donors with searchable access by
investigators
790. Brock J, Brown CC, Boucher J, Rippon G. The temporal binding deficit hypothesis of
autism. Dev Psychopathol 2002;14(2):209-224.
Ref ID: 4671
Abstract: Frith has argued that people with autism show "weak central coherence," an
unusual bias toward piecemeal rather than configurational processing and a reduction in
the normal tendency to process information in context. However, the precise cognitive and
neurological mechanisms underlying weak central coherence are still unknown. We
propose the hypothesis that the features of autism associated with weak central coherence
result from a reduction in the integration of specialized local neural networks in the brain
caused by a deficit in temporal binding. The visuoperceptual anomalies associated with
weak central coherence may be attributed to a reduction in synchronization of
high-frequency gamma activity between local networks processing local features. The
failure to utilize context in language processing in autism can be explained in similar terms.
Temporal binding deficits could also contribute to executive dysfunction in autism and to
some of the deficits in socialization and communication
791. Brodal A. Neurological Anatomy in Relation to Clinical Medicine. 3 ed. New York: Oxford
University Press; 1981.
Ref ID: 2398
792. Broderick PA, Phelix CF. I. Serotonin (%-HT) within dopamine reward circuits signals
open-field behavior. II. Basis for 5-HT-DA interactions in cocaine dysfunctional behavior.
Neurosci Behav Rev 1997;21(3):227-260.
Ref ID: 2424
793. Broman S, Nichols PL, Shaughnessy P, Kennedy W. Retardation in Young Children:A
Developmental Study of Cognitive Deficit. Hillsdale, N.J.: Lawrence Erlbaum Associates;
1987.
Ref ID: 1262
794. Broman SH, Nichols PL, Kennedy WA. Preschool IQ: Prenatal and Early Developmental
Correlates. New York: John Wiley and Sons; 1975.
Ref ID: 1263
795. Brookhouser PE. Diseases of the inner ear and sensorineural deafness. In: Bluestone CD,
Stool SE, Kenna MA, editors. Pediatric Otolaryngology. 3 ed. Philadelphia PA: W.B.
Saunders; 1996:649-670.
Ref ID: 1886
796. Brookhouser PE, Worthington DW, Kelly WJ. Unilateral hearing loss in children.
Laryngoscope 1991;101(12 Pt 1):1264-1272.
Ref ID: 4161
Abstract: Recent reports suggest that early onset, severe unilateral sensorineural hearing
loss (USNHL) in children may be associated with significant deficits in auditory and
psycholinguistic skills and school performance. This report reviews a consecutive series of
324 children and adolescents (202 males, 122 females) with documented USNHL
evaluated at the Boys Town National Research Hospital. The left ear was affected in 168
(52%) and the right ear in 156 (48%). Based on speech frequency threshold averages (i.e.,
500, 1000, and 2000 Hz), the losses were classified by severity as follows: borderline, 43
(13%); mild, 51 (16%); moderate, 40 (12%); severe, 19 (6%); profound, 31 (10%), and
anacusic, 50 (15%). The remaining 90 children (28%) had high frequency losses (i.e.,
199
above 2000 Hz). The mean and median age of diagnosis were 8.78 years and 7.75 years.
Temporal bone imaging studies, auditory brainstem responses (ABRs), and vestibular
evaluations were performed on selected cases. Etiology was uncertain in 34.8% of cases,
while hereditary factors (12.6%), head trauma (10.8%), and perinatal risk factors (10.7%)
were the most commonly identified etiologies. Thirty-one percent of the children had
scholastic or behavioral problems in school. A concerted effort aimed at early identification
and intervention in cases of USNHL is warranted
797. Brookhouser PE, Goldgar DE. Medical profile of the language-delayed child: otitis-prone
versus otitis-free. Int J Pediatr Otorhinolaryngol 1987;12:237-271.
Ref ID: 1280
798. Brookhouser PE, Hixon PK, Matkin ND. Early Childhood language delay: The
otolaryngologist's perspective. Laryngoscope 1979;89:1898-1913.
Ref ID: 593
799. Brooks-Gunn J, Liaw FR, Klebanov PK. Effects of early intervention on cognitive function of
low birth weight preterm infants. J Pediatr 1992;120(3):350-359.
Ref ID: 3220
Abstract: The Infant Health and Development Program is a randomized clinical trial to test
the efficacy of educational and family support services and pediatric follow-up, offered
during the first 3 years of life, in reducing the incidence of developmental delay in low birth
weight preterm infants at eight clinical sites (N = 985). It was hypothesized that larger
intervention effects would be found for the domains in which low birth weight preterm
infants are known to have problems, specifically visual-motor and spatial skills and
receptive language skills. These analyses explore the effects of the Infant Health and
Development Program on different domains of cognitive functioning. Cognitive domains are
identified by means of factor analysis of the intelligence tests used at 12, 24, and 36
months (Bayley Scales of Infant Development (including the Mental and Motor scales) at 12
and 24 months; the Stanford-Binet, Peabody Picture Vocabulary Test, and Beery Test of
Visual Motor Intergration at 36 months). Our results reveal that, although intervention
benefits accrue across cognitive domains at 24 and 36 months, gains are most pronounced
for receptive language and visual-motor and spatial skills
800. Brooks-Kayal A. Molecular mechanisms of cognitive and behavioral comorbidities of
epilepsy in children. Epilepsia 2011;52 Suppl 1:13-20.
Ref ID: 6842
Abstract: Intellectual and developmental disabilities (IDDs) such as autistic spectrum
disorders (ASDs) and epilepsies are heterogeneous disorders that have diverse etiologies
and pathophysiologies. The high rate of co-occurrence of these disorders, however,
suggests potentially shared underlying mechanisms. A number of well-known genetic
disorders share epilepsy, intellectual disability, and autism as prominent phenotypic
features, including tuberous sclerosis complex, Rett syndrome, and fragile X syndrome. In
addition, mutations of several genes involved in neurodevelopment, including ARX, DCX,
neuroligins, and neuropilin 2 have been identified in children with epilepsy, IDDs, ASDs, or
a combination of thereof. Finally, in animal models, early life seizures can result in cellular
and molecular changes that could contribute to learning and behavioral disabilities.
Increased understanding of the common genetic, molecular, and cellular mechanisms of
IDDs, ASDs, and epilepsy may provide insight into their underlying pathophysiology and
elucidate new therapeutic approaches for these conditions
801. Brooks AD, Berninger VW, Abbott RD. Letter naming and letter writing reversals in children
with dyslexia: momentary inefficiency in the phonological and orthographic loops of working
memory
19. Dev Neuropsychol 2011;36(7):847-868.
Ref ID: 7356
200
Abstract: Given mounting evidence for working memory impairments in dyslexia, letter
reversals during rapid automatic letter naming (phonological loop) or rapid automatic letter
writing (orthographic loop) may reflect momentary inefficiency of working memory. Few of
the children, with or without dyslexia, in a multi-generational family genetics study,
produced reversals, but those with dyslexia produced more than those without dyslexia.
Working-memory component predictors (word storing and processing units, phonological
and orthographic loops, and executive functions) in regressions differentiated children with
dyslexia (average age 11) who did and did not make reversals, predicted the number of
reversals on specific letter naming or letter writing tasks, and explained unique variance in
reading and writing outcomes. Although reversals are not a hallmark defining feature of
dyslexia, children who produce reversals may benefit from instruction designed to develop
specific working memory components and their efficient coordination in time
802. Brooks DN. Otitis media with effusion and academic attainment. Int J Pediatr
Otorhinolaryngol 1986;12:237-271.
Ref ID: 821
803. Brooks DN. Acoustic impedance measurement as screening procedure in children:
Discussion paper. Journal of the Royal Society of Medicine 1985;78:119-121.
Ref ID: 595
804. Brooks PJ, Cheng TF, Cooper L. Do all of the neurologic diseases in patients with DNA
repair gene mutations result from the accumulation of DNA damage? DNA Repair (Amst)
2008;7(6):834-848.
Ref ID: 5679
Abstract: The classic model for neurodegeneration due to mutations in DNA repair genes
holds that DNA damage accumulates in the absence of repair, resulting in the death of
neurons. This model was originally put forth to explain the dramatic loss of neurons
observed in patients with xeroderma pigmentosum neurologic disease, and is likely to be
valid for other neurodegenerative diseases due to mutations in DNA repair genes.
However, in trichiothiodystrophy (TTD), Aicardi-Goutieres syndrome (AGS), and Cockayne
syndrome (CS), abnormal myelin is the most prominent neuropathological feature. Myelin is
synthesized by specific types of glial cells called oligodendrocytes. In this review, we focus
on new studies that illustrate two disease mechanisms for myelin defects resulting from
mutations in DNA repair genes, both of which are fundamentally different than the classic
model described above. First, studies using the TTD mouse model indicate that TFIIH acts
as a co-activator for thyroid hormone-dependent gene expression in the brain, and that a
causative XPD mutation in TTD results in reduction of this co-activator function and a
dysregulation of myelin-related gene expression. Second, in AGS, which is caused by
mutations in either TREX1 or RNASEH2, recent evidence indicates that failure to degrade
nucleic acids produced during S-phase triggers activation of the innate immune system,
resulting in myelin defects and calcification of the brain. Strikingly, both myelin defects and
brain calcification are both prominent features of CS neurologic disease. The similar
neuropathology in CS and AGS seems unlikely to be due to the loss of a common DNA
repair function, and based on the evidence in the literature, we propose that vascular
abnormalities may be part of the mechanism that is common to both diseases. In summary,
while the classic DNA damage accumulation model is applicable to the neuronal death due
to defective DNA repair, the myelination defects and brain calcification seem to be better
explained by quite different mechanisms. We discuss the implications of these different
disease mechanisms for the rational development of treatments and therapies
805. Brooks WH. Autoimmune disorders result from loss of epigenetic control following
chromosome damage. Med Hypotheses 2005;64(3):590-598.
Ref ID: 6552
Abstract: Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis share
common features in typical cases such as: adult onset, central nervous system problems,
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female predominance, episodes triggered by a variety of stresses, and an autoimmune
reaction. At times, the different disorders are found in the same patient or close relatives.
These disorders are quite complex but they may share a common mechanism that results
in different, tissue-specific consequences based on the cell types in which the mechanism
occurs. Here, it is hypothesized that DNA damage can lead to loss of epigenetic control,
particularly when the damaged chromatin is distributed unevenly to daughter cells.
Expression of genes and pseudogenes that have lost their epigenetic restraints can lead to
autoimmune disorders. Loss of control of genes on the X chromosome and loss of control
of polyamine expression are discussed as examples of this mechanism
806. Brothers L, Ring B, Kling A. Response of neurons in the macaque amygdala to complex
social stimuli. Behav Brain Res 1990;41(3):199-213.
Ref ID: 3168
Abstract: The presence of neurons in macaque temporal cortex and amygdala which fire
selectively in response to social stimuli has been demonstrated by several investigators.
The extent to which such neuronal populations may respond to a broad range of social
features, including expressive movements and interactions, has not been fully explored due
to the difficulty of presenting such complex stimuli in a controlled fashion. We describe a
method for presenting moving segments of macaque behavior, visual and auditory, to
animal subjects during single unit recording. The method permits a broad range of stimuli to
be used both as probes and as controls. In addition, a novel technique for monitoring eye
position in alert macaque subjects is described. We present results from the medial
amygdala and adjacent cortex, demonstrating that neurons in these regions respond
selectively to features of the social environment
807. Broughton BC, Berneburg M, Fawcett H et al. Two individuals with features of both
xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical
outcomes of mutations in the XPD gene. Hum Mol Genet 2001;10(22):2539-2547.
Ref ID: 6035
Abstract: The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription
factor TFIIH with DNA helicase activity. TFIIH has two functions, in basal transcription and
nucleotide excision repair. Mutations in XPD that affect DNA repair but not transcription
result in the skin cancer-prone disorder, xeroderma pigmentosum (XP). If transcription is
also affected, the result is the multi-system disorder trichothiodystrophy (TTD), in which
there is no skin cancer predisposition, or in rare cases, XP combined with Cockayne
syndrome. Up till now there have been no reports of combined clinical features of XP and
TTD. We have now identified two patients with some features of both these disorders. One
of these, XP189MA, a 3-year-old girl with sun sensitivity, mental and physical
developmental delay, has XPD mutations not previously reported, and barely detectable
levels of nucleotide excision repair. The other, XP38BR, a 28-year-old woman with sun
sensitivity, pigmentation changes and skin cancers typical of XP, has a mutation that has
been identified previously, but only in TTD patients with no features of XP. The level of
repair of UV damage in XP38BR is substantially higher than that in other patients with the
same mutation. With both patients, polarized light microscopy revealed a 'tiger-tail'
appearance of the hair, and amino acid analysis of the hair shafts show levels of
sulfur-containing proteins intermediate between those of normal and TTD individuals. Our
findings highlight the complexities of genotype-phenotype relationships in the XPD gene
808. Brown AS. The environment and susceptibility to schizophrenia. Prog Neurobiol
2011;93(1):23-58.
Ref ID: 7083
Abstract: In the present article the putative role of environmental factors in schizophrenia is
reviewed and synthesized. Accumulating evidence from recent studies suggests that
environmental exposures may play a more significant role in the etiopathogenesis of this
disorder than previously thought. This expanding knowledge base is largely a consequence
of refinements in the methodology of epidemiologic studies, including birth cohort
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investigations, and in preclinical research that has been inspired by the evolving literature
on animal models of environmental exposures. This paper is divided into four sections. In
the first, the descriptive epidemiology of schizophrenia is reviewed. This includes general
studies on incidence, prevalence, and differences in these measures by urban-rural,
neighborhood, migrant, and season of birth status, as well as time trends. In the second
section, we discuss the contribution of environmental risk factors acting during fetal and
perinatal life; these include infections [e.g. rubella, influenza, Toxoplasma gondii (T. gondii),
herpes simplex virus type 2 (HSV-2)], nutritional deficiencies (e.g., famine, folic acid, iron,
vitamin D), paternal age, fetal/neonatal hypoxic and other obstetric insults and
complications, maternal stress and other exposures [e.g. lead, rhesus (Rh) incompatibility,
maternal stress]. Other putative neurodevelopmental determinants, including cannabis,
socioeconomic status, trauma, and infections during childhood and adolescence are also
covered. In the third section, these findings are synthesized and their implications for
prevention and uncovering biological mechanisms, including oxidative stress, apoptosis,
and inflammation, are discussed. Animal models, including maternal immune activation,
have yielded evidence suggesting that these exposures cause brain and behavioral
phenotypes that are analogous to findings observed in patients with schizophrenia. In the
final section, future studies including new, larger, and more rigorous epidemiologic
investigations, and research on translational and clinical neuroscience, gene-environment
interactions, epigenetics, developmental trajectories and windows of vulnerability, are
elaborated upon. These studies are aimed at confirming observed risk factors, identifying
new environmental exposures, elucidating developmental mechanisms, and shedding
further light on genes and exposures that may not be identified in the absence of these
integrated approaches. The study of environmental factors in schizophrenia may have
important implications for the identification of causes and prevention of this disorder, and
offers the potential to complement, and refine, existing efforts on explanatory
neurodevelopmental models
809. Brown C, Gruber T, Boucher J, Rippon G, Brock J. Gamma abnormalities during perception
of illusory figures in autism. Cortex 2005;41(3):364-376.
Ref ID: 4706
Abstract: This experiment was designed to test the hypothesis that perceptual
abnormalities in autism might be associated with alteration of induced gamma activity
patterns overlying visual cortical regions. EEG was recorded from six adolescents with
autism and eight controls matched on chronological age, and verbal and nonverbal mental
age, whilst identifying the presence or absence of an illusory Kanizsa shape. Although
there were no reaction time or accuracy differences between the groups there were
significant task-related differences in cortical activity. Control participants showed typical
gamma-band activity over parietal regions at around 350 msec post onset of shape trials,
similar to gamma patterns found in previous studies with non-impaired adults. In contrast,
autistic participants showed overall increased activity, including an early 100 msec gamma
peak and a late induced peak, 50 to 70 msec earlier than that shown by the control group.
We interpret the abnormal gamma activity to reflect decreased "signal to noise" due to
decreased inhibitory processing. In this experiment we did not establish a link between
altered perception and abnormal gamma, as the autistic participants' behaviour did not
differ from the controls. Future work should be designed to replicate this phenomenon and
establish the perceptual consequences of altered gamma activity
810. Brown EC, Aman MG, Havercamp SM. Factor analysis and norms for parent ratings on the
Aberrant Behavior Checklist - community for young people in special education. Res Dev
Disabil 2002;in press.
Ref ID: 3558
811. Brown J, Prelock PA. Brief report: The impact of regression on language development in
autism. J Autism Dev Disord 1995;25(3):305-309.
Ref ID: 1514
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812. Brown KS. Genetic and environmental factors in profound prelingual deafness. Med Clin
North Am 1969;53:741-772.
Ref ID: 1796
813. Brown LL, Feldman SM, Smith DM, Cavanaugh JR, Ackermann RF, Graybiel AM.
Differential metabolic activity in the striosome and matrix compartments of the rat striatum
during natural behaviors. J Neurosci 2002;22(1):305-314.
Ref ID: 4921
Abstract: The striosome and matrix compartments of the striatum are clearly identified by
their neurochemical expression patterns and anatomical connections. To determine
whether these compartments are distinguishable functionally, we used [14C]deoxyglucose
metabolic mapping in the rat and tested whether neutral behavioral states (free movement,
gentle restraint, and focal tactile stimulation under gentle restraint) were associated with
regions of high metabolic activity in the matrix, in striosomes, or in both. We identified
metabolic peaks in the striatum by means of image analysis, striosome-matrix boundaries
by [3H]naloxone binding, and primary somatosensory corticostriatal input clusters by
injections of anterograde tracer into electrophysiologically identified sites in SI. Peak
metabolic activity was primarily confined to the matrix compartment under each behavioral
condition. These findings show that during relatively neutral behavioral conditions the
balance of activity between the two compartments favors the matrix and suggest that this
balance is present in the striatum as part of normal behavior and processing of afferent
activity
814. Brown MC, Ledwith JV, III. Projections of thin (type-II) and thick (type-I) auditory-nerve
fibers into the cochlear nucleus of the mouse. Hear Res 1990;49(1-3):105-118.
Ref ID: 3401
Abstract: Injections of horseradish peroxidase into the mouse spiral ganglion were used to
label type-I and type-II afferent fibers. Axons presumed to be from type-II spiral ganglion
cells because of their small diameter (less than 0.7 microns) and lack of nodes of Ranvier
were traced to their terminations in the cochlear nucleus. Thicker fibers presumed to be
from type-I ganglion cells were also reconstructed. Type- I and type-II axons labeled by
basal turn injections bifurcate together in the dorsal part of the auditory nerve root, forming
a branch that ascends into the anteroventral cochlear nucleus and a branch that descends
into the posteroventral cochlear nucleus. Type-I fibers formed many collaterals ending in
terminal swellings whereas type-II fibers were almost unbranched. Swellings from type-I
and type-II fibers were often formed alongside one another. Examples of this proximity
include terminal swellings of root collaterals in the auditory nerve root, as well as type-II en
passant swellings and type-I terminal swellings throughout the ventral cochlear nucleus.
The projections are dissimilar, however, since every type-II fiber projects at least one
collateral to the granule-cell lamina. These collaterals usually end in neuropil forming the
border between the ventral cochlear nucleus and the granule-cell lamina. In this border
region, the type-II terminals overlap with those of branches from thick axons of the
olivocochlear (efferent) bundle. Type-II fibers also differ from type-I fibers by only rarely
coursing into the dorsal cochlear nucleus and by forming very few terminal swellings. En
passant swellings, however, are numerous on type-II fibers, with ellipsoidal-shaped
swellings prominent in the nerve root, and angular and complex-shaped swellings common
nearer the terminals. We suggest that the latter swellings are associated with type-II
synapses whereas the ellipsoidal swellings represent non-synaptic structures
815. Brown P, Rothwell JC, Thompson PD, Marsden CD. Propriospinal myoclonus: evidence for
spinal "pattern" generators in humans. Mov Disord 1994;9(5):571-576.
Ref ID: 2217
Abstract: The clinical and electrophysiological characteristics of eight patients with
propriospinal myoclonus are described. Myoclonus developed within days or weeks of
cervical trauma in half the patients. Seven cases had axial flexion jerks, and one axial
extension jerks. Myoclonic EMG activity consisted of repetitive bursts with a frequency of
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1-7 Hz. The jerks in three of the cases were comprised of alternating and rhythmic bursts of
EMG activity in rectus abdominis and the paraspinal muscles. From these new
observations, it is proposed that cervical trauma can lead to the partial release of a spinal
pattern generator. The latter is capable of recruiting muscles through long propriospinal
pathways into complex rhythmic activity
816. Brown R, Hobson RP, Lee A, Stevenson J. Are there "autistic-like" features in congenitally
blind children? J Child Psychol Psychiatry 1997;38:693-703.
Ref ID: 2714
Abstract:
Twenty-four congenitally blind children between 3 and 9 years of age were studied for the
prevalence of "autistic-like" features, as assessed by teacher reports and by systematic
observations of the children's behaviour. A comparison between the 15 blind children who
had IQs over 70 and 10 sighted children group-matched for age and verbal ability revealed
that a number of autistic-like features were more common in the blind. When the nine blind
children who had IQs less than 70 were compared with nine group-matched autistic
children, the picture that emerged was of substantial overlap in clinical presentation,
despite subtle differences on clinical impression. Similar results were obtained when blind
subgroups were reconstituted according to the children's nonautistic or autistic-like clinical
presentation, rather than IQ. These findings are discussed in relation to competing theories
concerning the development of autism and "theory of mind".
817. Brown R. A First Language: The Early Stages. Cambridge, MA: Harvard University Press;
1973.
Ref ID: 914
818. Brown TR. Intrathecal baclofen therapy in children with cerebral palsy. Arch Phys Med
Rehabil 2003;84(4):624.
Ref ID: 3872
819. Brown TT, Jernigan TL. Brain development during the preschool years. Neuropsychol Rev
2012;22(4):313-333.
Ref ID: 7665
Abstract: The preschool years represent a time of expansive mental growth, with the initial
expression of many psychological abilities that will continue to be refined into young
adulthood. Likewise, brain development during this age is characterized by its "blossoming"
nature, showing some of its most dynamic and elaborative anatomical and physiological
changes. In this article, we review human brain development during the preschool years,
sampling scientific evidence from a variety of sources. First, we cover neurobiological
foundations of early postnatal development, explaining some of the primary mechanisms
seen at a larger scale within neuroimaging studies. Next, we review evidence from both
structural and functional imaging studies, which now accounts for a large portion of our
current understanding of typical brain development. Within anatomical imaging, we focus
on studies of developing brain morphology and tissue properties, including diffusivity of
white matter fiber tracts. We also present new data on changes during the preschool years
in cortical area, thickness, and volume. Physiological brain development is then reviewed,
touching on influential results from several different functional imaging and recording
modalities in the preschool and early school-age years, including positron emission
tomography (PET), electroencephalography (EEG) and event-related potentials (ERP),
functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and
near-infrared spectroscopy (NIRS). Here, more space is devoted to explaining some of the
key methodological factors that are required for interpretation. We end with a section on
multimodal and multidimensional imaging approaches, which we believe will be critical for
increasing our understanding of brain development and its relationship to cognitive and
behavioral growth in the preschool years and beyond
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820. Brown TT, Lugar HM, Coalson RS, Miezin FM, Petersen SE, Schlaggar BL. Developmental
Changes in Human Cerebral Functional Organization for Word Generation. Cereb Cortex
2004.
Ref ID: 4360
Abstract: A fundamental issue in cognitive neuroscience is the nature of developmental
changes in human cerebral functional organization for higher cognitive functions.
Event-related functional magnetic resonance imaging was used to measure developmental
changes in the functional neuroanatomy subserving controlled lexical association. First,
brain regions showing significant differences in activity between school-age children and
young adults, despite equivalent task performance, were identified. Then, activity in these
regions was more fully characterized in individuals spanning the ages of 7-32 years old.
Cross-sectional and regression analyses showed systematic increases and decreases in
levels of activity over age, by region. Age-related increases in activity were primarily newly
recruited, later-stage processing regions, such as in left frontal and left parietal cortex.
Decreases, on the other hand, were all positive activations that attenuated with age and
were found across a wider neuroanatomical range, including earlier processing regions
such as bilateral extrastriate cortex. The hemodynamic magnitude, neuroanatomical
location and maturational timecourse of these progressive and regressive changes have
implications for models of the developing specialization in human cerebral functional
organization
821. Brown WA, Cammuso K, Sachs H et al. Autism-related language, personality, and
cognition in people with absolute pitch: results of a preliminary study. J Autism Dev Disord
2003;33(2):163-167.
Ref ID: 4253
Abstract: Reports of a relatively high prevalence of absolute pitch (AP) in autistic disorder
suggest that AP is associated with some of the distinctive cognitive and social
characteristics seen in autism spectrum disorders. Accordingly we examined cognition,
personality, social behavior, and language in 13 musicians with strictly defined AP (APS)
and 33 musician controls (MC) without AP using standardized interviews and tests
previously applied to identify the broad autism phenotype seen in the relatives of autistic
probands. These included the Pragmatic Rating Scale (PRS) (social aspects of language)
the Personality Assessment Schedule (PAS) (rigidity, aloofness, anxiety/worry,
hypersensitivity), and WAIS performance subtests (PIQ). On the basis of their behavior in
the interviews, subjects were classified as socially eccentric, somewhat eccentric, or not
eccentric. Forty-six percent of the APS, but only 15% of the MC, were classified as socially
eccentric (p < .03). APS but not MC showed higher scores on block design than on the
other PIQ tests (p < .06), a PIQ pattern seen in autism spectrum disorders. Although APS
and MC did not differ significantly on other measures it is of note that APS mean scores on
the PRS and PAS (5.69, 4.92) were almost twice as high as those for the MC (3.03, 2.45).
Thus, musicians with AP show some of the personality, language, and cognitive features
associated with autism. Piecemeal information processing, of which AP is an extreme and
rare example, is characteristic of autism and may be associated as well with subclinical
variants in language and behavior. We speculate that the gene or genes that underlie AP
may be among the genes that contribute to autism
822. Brownlee RC, Jr., De Loache WR, Cowan CC, Jr., Jackson HP. Otitis media in children:
Incidence, treatment and prognosis in pediatric practice. J Pediatr 1969;75:636-642.
Ref ID: 822
823. Broyd SJ, Demanuele C, Debener S, Helps SK, James CJ, Sonuga-Barke EJ.
Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci
Biobehav Rev 2009;33(3):279-296.
Ref ID: 6998
Abstract: In this review we are concerned specifically with the putative role of the
default-mode network (DMN) in the pathophysiology of mental disorders. First, we define
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the DMN concept with regard to its neuro-anatomy, its functional organisation through low
frequency neuronal oscillations, its relation to other recently discovered low frequency
resting state networks, and the cognitive functions it is thought to serve. Second, we
introduce methodological and analytical issues and challenges. Third, we describe putative
mechanisms proposed to link DMN abnormalities and mental disorders. These include
interference by network activity during task performance, altered patterns of antagonism
between task specific and non-specific elements, altered connectively and integrity of the
DMN, and altered psychological functions served by the network DMN. Fourth, we review
the empirical literature systematically. We relate DMN dysfunction to dementia,
schizophrenia, epilepsy, anxiety and depression, autism and attention deficit/hyperactivity
disorder drawing out common and unique elements of the disorders. Finally, we provide an
integrative overview and highlight important challenges and tasks for future research
824. Brudnak MA. Application of genomeceuticals to the molecular and immunological aspects
of autism. Med Hypotheses 2001;57(2):186-191.
Ref ID: 3507
Abstract: Autism is a developmental disease affecting as many as 1 in 300 children and is
often characterized as a mental disorder originating in infancy that is associated with
self-absorption, inability to interact socially, behavior, and language dysfunction (e.g.
echolalia). Current theories indicate an important role of diet in the development of disease.
It is thought that, as a result of maldigestion of casein and gluten, opioid-type peptides, or
exorphins, are produced. Additionally, because of the time-frame of development of the
disease, there has been an association with childhood vaccination. Consequently,
prevailing therapies attempt to address these causes in one, or a combination, of three
ways: diet restriction (removing casein and gluten); supplementation with exogenous
enzymes; and probiotic bacteria. Until recently, none of the therapies addressed the
molecular mechanisms that may be at work in the development and progression of autism.
This paper presents potential molecular and cellular mechanism related to autism as well
as discusses their application to the treatment of the disease through the application of
genomeceuticals. Additionally, a link between developmentally associated aberrant
immune and inflammatory responses, and autism is suggested and explored
825. Brugha TS, McManus S, Bankart J et al. Epidemiology of autism spectrum disorders in
adults in the community in England. Arch Gen Psychiatry 2011;68(5):459-465.
Ref ID: 6983
Abstract: CONTEXT: To our knowledge, there is no published information on the
epidemiology of autism spectrum disorders (ASDs) in adults. If the prevalence of autism is
increasing, rates in older adults would be expected to be lower than rates among younger
adults. OBJECTIVE: To estimate the prevalence and characteristics of adults with ASD
living in the community in England. DESIGN: A stratified, multiphase random sample was
used in the third national survey of psychiatric morbidity in adults in England in 2007.
Survey data were weighted to take account of study design and nonresponse so that the
results were representative of the household population. SETTING: General community (ie,
private households) in England. PARTICIPANTS: Adults (people 16 years or older). MAIN
OUTCOME MEASURES: Autism Diagnostic Observation Schedule, Module 4 in phase 2
validated against the Autism Diagnostic Interview-Revised and Diagnostic Interview for
Social and Communication Disorders in phase 3. A 20-item subset of the Autism-Spectrum
Quotient self-completion questionnaire was used in phase 1 to select respondents for
phase 2. Respondents also provided information on sociodemographics and their use of
mental health services. RESULTS: Of 7461 adult participants who provided a complete
phase 1 interview, 618 completed phase 2 diagnostic assessments. The weighted
prevalence of ASD in adults was estimated to be 9.8 per 1000 (95% confidence interval,
3.0-16.5). Prevalence was not related to the respondent's age. Rates were higher in men,
those without educational qualifications, and those living in rented social
(government-financed) housing. There was no evidence of increased use of services for
mental health problems. CONCLUSIONS: Conducting epidemiologic research on ASD in
207
adults is feasible. The prevalence of ASD in this population is similar to that found in
children. The lack of an association with age is consistent with there having been no
increase in prevalence and with its causes being temporally constant. Adults with ASD
living in the community are socially disadvantaged and tend to be unrecognized
826. Brumback RA, Yoder FW, Andrews AD, Peck GL, Robbins JH. Normal pressure
hydrocephalus: recognition and relationship to neurological abnormalities in Cockayne's
syndrome. Arch Neurol 1978;35:337-345.
Ref ID: 3056
827. Bruneau N, Roux S, Adrien JL, Barthelemy C. Auditory associative cortex dysfunction in
children with autism: evidence from late auditory evoked potentials (N1 wave-T complex).
Clin Neurophysiol 1999;110(11):1927-1934.
Ref ID: 3612
Abstract: OBJECTIVES: Auditory processing at the cortical level was investigated with late
auditory evoked potentials (N1 wave-T complex) in 4-8-year-old autistic children with
mental retardation and compared to both age-matched normal and mentally retarded
children (16 children in each group). METHODS: Two negative peaks which occurred in the
80-200 ms latency range were analyzed according to stimulus intensity level (50 to 80 dB
SPL): the first culminated at fronto-central sites (N1b) and the second at bitemporal sites
(N1c, equivalent to Tb of the T complex). The latter wave was the most prominent and
reliable response in normal children at this age. RESULTS: Our results in autistic children
indicated abnormalities of this wave with markedly smaller amplitude at bitemporal sites
and pronounced peak latency delay (around 20 ms). Moreover, in both reference groups
the intensity effect was found on both sides whereas in autistic children it was absent on
the left side but present on the right. CONCLUSION: These findings in autistic children
showing very disturbed verbal communication argue for dysfunction in brain areas involved
in N1c generation i.e., the auditory associative cortex in the lateral part of the superior
temporal gyrus, with more specific left side defects when auditory stimulus have to be
processed
828. Bruneau N, Roux S, Guerin P, Garreau B, LeLord G. Auditory stimulus intensity responses
and frontal midline theta rhythm. Electroenceph Clin Neurophysiol 1993;86(3):213-216.
Ref ID: 1479
829. Bruneau N, Dourneau MC, Garreau B, Pourcelot L, LeLord G. Blood flow response to
auditory stimulation in normal, mentally retarded, and autistic children: A preliminary
transcranial Doppler ultrasonographic study of the middle cerebral arteries. Biol Psychiatry
1992;32(8):691-699.
Ref ID: 1659
Abstract: Using the noninvasive transcranial ultrasonic Doppler method, flow dynamics of
the middle cerebral arteries were investigated in relation to auditory stimulations in 12
children with autistic behavior compared with 12 normal controls and 10 mentally retarded
children. In normal children, auditory stimulation evoked lateralized modifications: blood
flow increased and resistance index decreased on the left side; such modifications were not
recorded on the right side. This pattern should indicate vasodilatation mechanisms induced
by changes in the metabolism of the brain areas supplied by the left middle cerebral
arteries (MCA). Although less asymmetrical, this pattern was also found in the mentally
retarded children. Autistic children significantly differed from these two groups. They
displayed a symmetric pattern of responses with a blood flow decrease and
resistance-index increase on both sides; this could suggest abnormal metabolic
mechanisms induced by auditory stimulation in autistic children and could be related to the
previous hypothesis of impairment in the development of cerebral lateralization in autism.
These preliminary results show that transcranial Doppler ultrasonography may be a
valuable and practicable tool for the noninvasive study of evoked blood flow responses in
psychopathology
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830. Brunger JW, Murray GS, O'Riordan M, Matthews AL, Smith RJ, Robin NH. Parental
attitudes toward genetic testing for pediatric deafness. Am J Hum Genet
2000;67(6):1621-1625.
Ref ID: 6453
Abstract: Recent molecular genetic advances have resulted in genetic testing becoming an
option for deaf individuals and their families. However, there is little information about the
interest in such testing. To investigate this issue, parents with normal hearing who have
one or more deaf children were surveyed about their attitudes toward diagnostic, carrier,
and prenatal genetic testing for deafness. This population was chosen because it
represents the majority of individuals who are encountered in clinical practice, given that
90%-95% of deaf individuals are born to persons with normal hearing. Of 328 surveys
distributed, 96 were completed and returned. Of the respondents, 96% recorded a positive
attitude toward genetic testing for deafness, including prenatal testing, although none would
use this information to terminate an affected pregnancy. All respondents had a poor
understanding of genetics, with 98% both incorrectly estimating the recurrence risk of
deafness and misunderstanding the concept of inheritance. Notably, these findings were
similar in the group who had had genetic testing for their children and in the group who had
not, suggesting either that the parents who received genetic testing did not receive genetic
counseling or that the counseling was not effective. On the basis of these results, it was
concluded that this population is interested in the use of genetic testing and that testing
should not be done without first providing formal genetic counseling. Appropriate
counseling can help parents to understand the risks, benefits, and limitations of genetic
testing
831. Brunham LR, Hayden MR. Medicine. Whole-genome sequencing: the new standard of
care? Science 2012;336(6085):1112-1113.
Ref ID: 7197
832. Bruni O, Ferri R, Novelli L et al. Slow EEG amplitude oscillations during NREM sleep and
reading disabilities in children with dyslexia. Dev Neuropsychol 2009;34(5):539-551.
Ref ID: 7230
Abstract: STUDY OBJECTIVES: To analyze non-rapid eye movement (NREM) sleep
microstructure of children with dyslexia, by means of cyclic alternating pattern (CAP)
analysis and to correlate CAP parameters with neuropsychological measures. DESIGN:
Cross-sectional study using polysomnographic recordings and neuropsychological
assessments. Setting: Sleep laboratory in academic center. PARTICIPANTS: Sixteen
subjects with developmental dyslexia (mean age 10.8 years) and 11 normally reading
children (mean age 10.1 years) underwent overnight polysomnographic recording.
Intervention: N/A. MEASUREMENTS AND RESULTS: Sleep architecture parameters only
showed some statistically significant differences: number of sleep stage shifts per hour of
sleep, percentage of N3, and number of R periods were significantly lower in dyslexic
children versus controls. CAP analysis revealed a higher total CAP rate and A1 index in
stage N3. A2% and A2 index in stage N2 and N3 were lower in dyslexic children while no
differences were found for A3 CAP subtypes. The correlation analysis between CAP
parameters and cognitive-behavioral measures showed a significant positive correlation
between A1 index in N3 with Verbal IQ, full-scale IQ, and Memory and Learning Transfer
reading test; while CAP rate in N3 was positively correlated with verbal IQ.
CONCLUSIONS: To overcome reading difficulties, dyslexic subjects overactivate
thalamocortical and hippocampal circuitry to transfer information between cortical posterior
and anterior areas. The overactivation of the ancillary frontal areas could account for the
CAP rate modifications and mainly for the increase of CAP rate and of A1 index in N3 that
seem to be correlated with IQ and reading abilities
833. Bruni O, Ferri R, Novelli L et al. Sleep spindle activity is correlated with reading abilities in
developmental dyslexia. Sleep 2009;32(10):1333-1340.
Ref ID: 7231
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Abstract: STUDY OBJECTIVES: To analyze sleep architecture of children with dyslexia, by
means of conventional parameters and EEG spectral analysis and to correlate sleep
parameters and EEG spectra with neuropsychological measures. DESIGN: Cross-sectional
study involving validated sleep questionnaires, neuropsychological scales, and
polysomnographic recordings. SETTING: Sleep laboratory in academic center.
PARTICIPANTS: Sixteen subjects with developmental dyslexia (mean age 10.8 years) and
11 normally reading children (mean age 10.1 years). All the subjects underwent overnight
polysomnographic recording; EEG power spectra were computed from the Cz derivation
and spindle density was calculated during sleep stages N2. INTERVENTION: N/A.
MEASUREMENTS AND RESULTS: Dyslexic children showed an increase in power of
frequency bands between 0.5-3 Hz and 11-12 Hz in stage N2 and between 0.5-1 Hz in
stage N3; they also showed significantly increased spindle density during N2. The power of
the sigma band in N2 was positively correlated with the Word reading and MT reading
tests; similarly, spindle density was significantly correlated with the Word reading test. The
increased spindle activity and EEG sigma power in dyslexic subjects were found to be
correlated with the degree of dyslexic impairment. CONCLUSIONS: The correlation found
between sleep spindle activity and reading abilities in developmental dyslexia supports the
hypothesis of a role for NREM sleep and spindles in sleep-related neurocognitive
processing
834. Brunquell PJ, Russman BS, Lerer TJ. Sources of information used in diagnosing childhood
learning disabilities. Pediat Neurol 1991;7:342-346.
Ref ID: 1332
835. Brunson KL, Khan N, Eghbal-Ahmadi M, Baram TZ. Corticotropin (ACTH) acts directly on
amygdala neurons to down-regulate corticotropin-releasing hormone gene expression. Ann
Neurol 2001;49:304-312.
Ref ID: 3348
836. Brunstrom JE, Gray-Swain MR, Osborne PA, Pearlman AL. Neuronal heterotopias in the
developing cerebral cortex produced by neurotrophin-4. Neuron 1997;18(1):505-517.
Ref ID: 3105
837. Bryan GK, Riesen AH. Deprived somatosensory-motor experience in stumptailed monkey
neocortex: dendritic spine density and dendritic branching of layer IIIB pyramidal cells
[published erratum appears in J Comp Neurol 1989 Nov 22;289(4):709]. J Comp Neurol
1989;286(2):208-217.
Ref ID: 3223
Abstract: Infant macaque monkeys (Macaca arctoides) were individually raised to age 6
months in large clear cubes built into one wall of a control colony that allowed them visual
access to it but not tactile contact. The two deprivation conditions (Cond 2 and Cond 3)
were equal both in physical size and with respect to partial social isolation. They differed in
the degree of somatosensory-motor opportunity available during development in that the
Cond 2 chamber was empty, whereas Cond 3 contained ladders, a trapeze, and play
objects. Four monkeys from each of these conditions were compared with four
colony-reared (Cond CR) monkeys. Neuroanatomical changes were evaluated by using
light microscopy in Golgi-Cox-stained neocortex. Dendritic spines on the apical shafts of
layer IIIB pyramidal cells were counted in primary motor (MI), somatosensory (SI), and
visual (area 17, V1) cortical regions. Layer IIIB pyramidal neurons with somas of medium
size were selected from each cortical region and the density of apical dendritic spines
determined. The basilar dendritic branches of these same neurons were traced, and the
dendritic branching complexity was assessed in order to compare the sensitivity of the
dendritic spine and branching measures consequent to deprived rearing. The number of
apical dendritic spines was significantly reduced in Cond 2 when compared with either
Cond 3 or Cond CR (which did not differ from each other). This occurred in both MI and SI
cortex, but not in the visual cortex, the region used as a control for a global brain effect.
210
Branching complexity measured on the same pyramidal neurons was reduced only in MI
cortex of Cond 2. These results show spine density, a more direct measure of neuronal
connectivity, to be the more sensitive measure of early environmental deprivation. Also, the
enriched environment provided by Cond 3 relative to Cond 2 offset the effect of partial
social isolation such that both morphometric measures had values comparable to Cond CR
monkeys
838. Bryant J. The opening door. Cherry Gardens, S. Australia: Author; 1993.
Ref ID: 4251
839. Bryden MP. Cerebral specialization: clinical and experimental assessment. In: Boller F,
Grafman J, editors. Handbook of Neuropsychology. Vol. 1. Section 1: Introduction. 1 ed.
Amsterdam: Elsevier; 1988:143-159.
Ref ID: 2781
840. Bryson SE, Smith IM. Epidemiology of autism: Prevalence, associated characteristics, and
implications for research and service delivery. MRDDRR 1998;4(2):97-103.
Ref ID: 2113
841. Bryson SE. Epidemiology of autism: Overview and issues outstanding. In: Cohen DJ,
Volkmar FR, editors. Handbook of Autism and Pervasive Developmental Disorders. 2 ed.
New York: John Wiley & Sons; 1997:41-46.
Ref ID: 2163
842. Bryson SE, Clark BS, Smith IM. First report of a Canadian epidemiological study of autistic
syndromes. J Child Psychol Psychiatry 1988;29(4):433-445.
Ref ID: 1362
843. Brzustowicz LM, Hodgkinson KA, Chow EW, Honer WG, Bassett A.S. Location of major
susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science
2000;288:678-682.
Ref ID: 3091
844. Bucan M, Abrahams BS, Wang K et al. Genome-wide analyses of exonic copy number
variants in a family-based study point to novel autism susceptibility genes. PLoS Genet
2009;5(6):e1000536.
Ref ID: 6496
Abstract: The genetics underlying the autism spectrum disorders (ASDs) is complex and
remains poorly understood. Previous work has demonstrated an important role for
structural variation in a subset of cases, but has lacked the resolution necessary to move
beyond detection of large regions of potential interest to identification of individual genes.
To pinpoint genes likely to contribute to ASD etiology, we performed high density
genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE)
collection and contrasted results to those obtained for 1,488 healthy controls. Through
prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene
duplication events (gDups), we identified more than 150 loci harboring rare variants in
multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on
examination of an independent replication cohort comprised of 859 cases and an additional
1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole
gene duplications encompassing UBE3A and several other genes in the 15q11-q13 region,
were observed in the course of these analyses. Strong support was likewise observed for
previously unreported genes such as BZRAP1, an adaptor molecule known to regulate
synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no
controls (p = 2.3x10(-5)). Less is known about MDGA2, likewise observed to be
case-specific (p = 1.3x10(-4)). But, it is notable that the encoded protein shows an
unexpectedly high similarity to Contactin 4 (BLAST E-value = 3x10(-39)), which has also
211
been linked to disease. That hundreds of distinct rare variants were each seen only once
further highlights complexity in the ASDs and points to the continued need for larger
cohorts
845. Buchanan L, Kiss I, Burgess C. Phonological and semantic information in word and
nonword reading in a deep dyslexic patient. Brain Cognit 2000;43(1-3):65-68.
Ref ID: 5916
Abstract: Deep dyslexia is diagnosed when brain-injured, previously literate adults make
reading errors that include hallmark semantic paralexias (e.g., reading HEART as BLOOD)
and are also impaired at reading nonwords (e.g., FRIP). The diversity of these symptoms
have led most researchers to conclude that there are multiple sources of impairment in this
syndrome and that one of the most critical is a failure to process phonological information
at a sublexical level. The patient (SD) reported in this study fits the deep dyslexia profile to
the extent that she makes several semantically related reading errors. She also shows the
classic frequency and image ability effects of the syndrome. However, as we report, she
does read some nonwords correctly and she shows a strong advantage for naming when
phonemic cues are presented. We discuss the performance of SD, on these preliminary
tasks, in terms of a phonological selection impairment
846. Buchsbaum MS, Siegel BVJr, Wu JC, Hazlett E, Sicotte N, Haier R. Brief report: Attention
performance in autism and regional brain metabolic rate assessed by positron emission
tomography. J Autism Dev Disord 1992;22(1):115-125.
Ref ID: 1679
847. Buchwald JS, Erwin R, Van Lancker D, Guthrie D, Schwafel J, Tanguay P. Midlatency
auditory evoked responses: P1 abnormalities in adult autistic subjects. Electroencephalogr
Clin Neurophysiol 1992;84(2):164-171.
Ref ID: 4697
Abstract: MLR recordings from a group of 11 high-functioning adult autistic subjects were
compared with those from a control group of 11 normal subjects. Components selected for
analysis were "Pa", the maximum positivity in the 25-40 msec latency range following
stimulus onset, "P1", the maximum positivity within the 50-65 msec latency range, and
"Nb," the maximum negative deflection in the 40-50 msec latency range. Statistical
analyses of amplitude and latency data were conducted using repeated measures analysis
of variance and t test group comparisons. The Pa component showed no significant
difference between autistic and control groups. However, 2 types of abnormality were noted
in the P1 component: (1) the P1 component was significantly smaller in the autistic subjects
at slow rates of stimulation, and (2) the autistic P1 did not change as rates of click
stimulation increased from 0.5 to 10/sec, in contrast to the normally produced P1
decrement. Data from the P1 model in the cat, and complementary data from the human,
closely link the generator substrate of the P1 potential to cholinergic components of the
ascending reticular activating system (RAS) and their thalamic target cells. This is the first
report of abnormal P1 responses in autism and strongly suggests that the RAS and/or its
post-synaptic thalamic targets may be dysfunctional in this syndrome
848. Buckley PF. The clinical stigmata of aberrant neurodevelopment in schizophrenia. Journal
of Nervous and Mental Diseases 1998;186(2):79-86.
Ref ID: 59
Abstract: The neurodevelopmental hypothesis of schizophrenia is currently a primary
etiopathological model for schizophrenia. Its tenets derive from observations of
epidemiological, postmortem, and brain imaging evidence of neurodevelopmental
deviance. Clinical stigmata of neurodevelopmental arrest include the presence of obstetric
complications, minor physical anomalies, abnormal dermatoglyphics, and childhood
neuromotor precursors of adult schizophrenic illness. The relative importance of these
stigmata and their relationship to brain imaging findings in schizophrenia are discussed
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849. Buckner RL, Krienen FM, Yeo BT. Opportunities and limitations of intrinsic functional
connectivity MRI. Nat Neurosci 2013;16(7):832-837.
Ref ID: 7736
Abstract: Intrinsic functional connectivity magnetic resonance imaging (fcMRI) has emerged
as a powerful tool for mapping large-scale networks in the human brain. Robust and
reliable functionally coupled networks can be detected in individuals that echo many known
features of anatomical organization. Features of brain organization have been discovered,
including descriptions of distributed large-scale networks interwoven throughout association
cortex, interactions (including anticorrelations) between brain networks and insights into the
topography of subcortical structures. But interpreting fcMRI is complicated by several
factors. Functional coupling changes dynamically, suggesting that it is constrained by, but
not fully dictated by, anatomic connectivity. Critically to study of between-group differences,
fcMRI is sensitive to head motion and to differences in the mental states of participants
during the scans. We discuss the potential of fcMRI in the context of its limitations
850. Buckner RL. The serendipitous discovery of the brain's default network. Neuroimage
2012;62(2):1137-1145.
Ref ID: 7737
Abstract: One of the most unexpected findings by functional neuroimaging has been the
discovery of the brain's default network - a set of brain regions that is spontaneously active
during passive moments. The default network's discovery was a fortunate accident that
occurred due to the inclusion of rest control conditions in early PET and functional MRI
studies. At first, the network was ignored. Later, its presence was shunned as evidence of
an experimental confound. Finally, it emerged as a mainstream target of focused study.
Here, I describe a personal perspective of the default network's serendipitous discovery
851. Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT. The organization of the human
cerebellum estimated by intrinsic functional connectivity. J Neurophysiol
2011;106(5):2322-2345.
Ref ID: 7738
Abstract: The cerebral cortex communicates with the cerebellum via polysynaptic circuits.
Separate regions of the cerebellum are connected to distinct cerebral areas, forming a
complex topography. In this study we explored the organization of cerebrocerebellar
circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from
1,000 subjects were registered using nonlinear deformation of the cerebellum in
combination with surface-based alignment of the cerebral cortex. The foot, hand, and
tongue representations were localized in subjects performing movements. fcMRI maps
derived from seed regions placed in different parts of the motor body representation yielded
the expected inverted map of somatomotor topography in the anterior lobe and the upright
map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by
estimating the principal cerebral target for each point in the cerebellum in a discovery
sample of 500 subjects and replicated the topography in 500 independent subjects. The
majority of the human cerebellum maps to association areas. Quantitative analysis of 17
distinct cerebral networks revealed that the extent of the cerebellum dedicated to each
network is proportional to the network's extent in the cerebrum with a few exceptions,
including primary visual cortex, which is not represented in the cerebellum. Like
somatomotor representations, cerebellar regions linked to association cortex have separate
anterior and posterior representations that are oriented as mirror images of one another.
The orderly topography of the representations suggests that the cerebellum possesses at
least two large, homotopic maps of the full cerebrum and possibly a smaller third map
852. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy,
function, and relevance to disease. Ann N Y Acad Sci 2008;1124:1-38.
Ref ID: 6999
Abstract: Thirty years of brain imaging research has converged to define the brain's default
network-a novel and only recently appreciated brain system that participates in internal
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modes of cognition. Here we synthesize past observations to provide strong evidence that
the default network is a specific, anatomically defined brain system preferentially active
when individuals are not focused on the external environment. Analysis of connectional
anatomy in the monkey supports the presence of an interconnected brain system.
Providing insight into function, the default network is active when individuals are engaged in
internally focused tasks including autobiographical memory retrieval, envisioning the future,
and conceiving the perspectives of others. Probing the functional anatomy of the network in
detail reveals that it is best understood as multiple interacting subsystems. The medial
temporal lobe subsystem provides information from prior experiences in the form of
memories and associations that are the building blocks of mental simulation. The medial
prefrontal subsystem facilitates the flexible use of this information during the construction of
self-relevant mental simulations. These two subsystems converge on important nodes of
integration including the posterior cingulate cortex. The implications of these functional and
anatomical observations are discussed in relation to possible adaptive roles of the default
network for using past experiences to plan for the future, navigate social interactions, and
maximize the utility of moments when we are not otherwise engaged by the external world.
We conclude by discussing the relevance of the default network for understanding mental
disorders including autism, schizophrenia, and Alzheimer's disease
853. Buckner RL, Kelley WM, Petersen SE. Frontal cortex contributes to human memory
formation. [Review] [55 refs]. Nature Neuroscience 1999;2(4):311-314.
Ref ID: 3002
Abstract: The contribution of medial temporal lobe structures to memory is well established.
However recent brain-imaging studies have indicated that frontal cortex may also be
involved in human memory formation. Specific frontal areas are recruited during a variety of
procedures that promote memory formation, and the laterality of these areas is influenced
by the type of information contained in the memory. Imaging methods that capture
momentary changes in brain activity have further shown that the likelihood of memory
formation correlates with the level of activity in these areas. These results, taken in the
context of other studies, suggest that memory formation depends on joint participation of
frontal and medial temporal lobe structures. [References: 55]
854. Buckner RL, Raichle ME, Miezin FM, Petersen SE. Functional anatomic studies of memory
retrieval for auditory words and visual pictures. J Neurosci 1996;16(19):6219-6235.
Ref ID: 3000
Abstract: Functional neuroimaging with positron emission tomography was used to study
brain areas activated during memory retrieval. Subjects (n = 15) recalled items from a
recent study episode (episodic memory) during two paired-associate recall tasks. The tasks
differed in that PICTURE RECALL required pictorial retrieval, whereas AUDITORY WORD
RECALL required word retrieval. Word REPETITION and REST served as two reference
tasks. Comparing recall with repetition revealed the following observations. (1) Right
anterior prefrontal activation (similar to that seen in several previous experiments), in
addition to bilateral frontal-opercular and anterior cingulate activations. (2) An anterior
subdivision of medial frontal cortex [pre-supplementary motor area (SMA)] was activated,
which could be dissociated from a more posterior area (SMA proper). (3) Parietal areas
were activated, including a posterior medial area near precuneus, that could be dissociated
from an anterior parietal area that was deactivated. (4) Multiple medial and lateral
cerebellar areas were activated. Comparing recall with rest revealed similar activations,
except right prefrontal activation was minimal and activations related to motor and auditory
demands became apparent (e.g., bilateral motor and temporal cortex). Directly comparing
picture recall with auditory word recall revealed few notable activations. Taken together,
these findings suggest a pathway that is commonly used during the episodic retrieval of
picture and word stimuli under these conditions. Many areas in this pathway overlap with
areas previously activated by a different set of retrieval tasks using stem-cued recall,
demonstrating their generality. Examination of activations within individual subjects in
relation to structural magnetic resonance images provided an-atomic information about the
214
location of these activations. Such data, when combined with the dissociations between
functional areas, provide an increasingly detailed picture of the brain pathways involved in
episodic retrieval tasks
855. Bucy PC, Thieman PW. Astrocytomas of the cerebellum. A study of a series of patients
operated upon over 28 years ago. Arch Neurol 1968;18(1):14-19.
Ref ID: 6780
856. Bugge M, Bruun-Petersen G, Brondum-Nielsen K et al. Disease associated balanced
chromosome rearrangements: a resource for large scale genotype-phenotype delineation
in man. J Med Genet 2000;37(11):858-865.
Ref ID: 4343
Abstract: Disease associated balanced chromosomal rearrangements (DBCRs), which
truncate, delete, or otherwise inactivate specific genes, have been instrumental for
positional cloning of many disease genes. A network of cytogenetic laboratories, Mendelian
Cytogenetics Network (MCN), has been established to facilitate the identification and
mapping of DBCRs. To get an estimate of the potential of this approach, we surveyed all
cytogenetic archives in Denmark and southern Sweden, with a population of approximately
6.6 million. The nine laboratories have performed 71 739 postnatal cytogenetic tests.
Excluding Robertsonian translocations and chromosome 9 inversions, we identified 216
DBCRs ( approximately 0.3%), including a minimum estimate of 114 de novo reciprocal
translocations (0.16%) and eight de novo inversions (0.01%). Altogether, this is six times
more frequent than in the general population, suggesting a causal relationship with the
traits involved in most of these cases. Of the identified cases, only 25 (12%) have been
published, including 12 cases with known syndromes and 13 cases with unspecified mental
retardation/congenital malformations. The remaining DBCRs were associated with a
plethora of traits including mental retardation, dysmorphic features, major congenital
malformations, autism, and male and female infertility. Several of the unpublished DBCRs
defined candidate breakpoints for nail-patella, Prader-Willi, and Schmidt syndromes, ataxia,
and ulna aplasia. The implication of the survey is apparent when compared with MCN;
altogether, the 292 participating laboratories have performed >2.5 million postnatal
analyses, with an estimated approximately 7500 DBCRs stored in their archives, of which
more than half might be causative mutations. In addition, an estimated 450-500 novel
cases should be detected each year. Our data illustrate that DBCRs and MCN are
resources for large scale establishment of phenotype-genotype relationships in man
857. Buie T, Campbell DB, Fuchs GJ, III et al. Evaluation, diagnosis, and treatment of
gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 2010;125
Suppl 1:S1-18.
Ref ID: 6676
Abstract: Autism spectrum disorders (ASDs) are common and clinically heterogeneous
neurodevelopmental disorders. Gastrointestinal disorders and associated symptoms are
commonly reported in individuals with ASDs, but key issues such as the prevalence and
best treatment of these conditions are incompletely understood. A central difficulty in
recognizing and characterizing gastrointestinal dysfunction with ASDs is the communication
difficulties experienced by many affected individuals. A multidisciplinary panel reviewed the
medical literature with the aim of generating evidence-based recommendations for
diagnostic evaluation and management of gastrointestinal problems in this patient
population. The panel concluded that evidence-based recommendations are not yet
available. The consensus expert opinion of the panel was that individuals with ASDs
deserve the same thoroughness and standard of care in the diagnostic workup and
treatment of gastrointestinal concerns as should occur for patients without ASDs. Care
providers should be aware that problem behavior in patients with ASDs may be the primary
or sole symptom of the underlying medical condition, including some gastrointestinal
disorders. For these patients, integration of behavioral and medical care may be most
215
beneficial. Priorities for future research are identified to advance our understanding and
management of gastrointestinal disorders in persons with ASDs
858. Buitelaar JK. Why have drug treatments been so disappointing? Novartis Found Symp
2003;251:235-244.
Ref ID: 4757
Abstract: The title of this contribution involves two consecutive questions: have the effects
of medication in autism indeed been disappointing? And if so, why? The answer to the first
question depends on whether one focuses on the core social and communicative deficits of
autism, or on various complicating behaviour problems. Attempts over the past decades to
develop drugs that specifically improve social and communicative functioning have failed.
Among the most ambitious attempts were medical interventions in the endogenous opioid
system that were motivated from animal models on the involvement of this system in
various aspects of social behaviour. By contrast, medications such as the newer
antipsychotics, psychostimulants, presynaptic noradrenergic blocking agents (clonidine and
guanfacine) and selective serotonin reuptake inhibitors were shown to reduce impairing
complicating symptoms of affective instability, irritability, hyperactivity and inattentiveness,
aggression, self-injury and stereotypies. The explanation for the medication-refractory
status of social and communicative deficits should be sought in at least two related factors:
(1) the as yet unidentified neurochemical basis of autism, and (2) the obvious lack of
involvement of the main neurotransmitter systems (dopamine, noradrenaline and serotonin)
in the pathophysiology of social and communicative behaviour
859. Buitelaar JK, Van der Gaag R, Cohen-Kettenis P, Melman CT. A randomized controlled
trial of risperidone in the treatment of aggression in hospitalized adolescents with
subaverage cognitive abilities. J Clin Psychiatry 2001;62(239):248.
Ref ID: 3560
860. Buitelaar JK, Willemsen-Swinkels SH. Autism: current theories regarding its pathogenesis
and implications for rational pharmacotherapy. Paediatr Drugs 2000;2(1):67-81.
Ref ID: 3929
Abstract: Autism is a pervasive developmental disorder that is aetiologically and clinically
heterogeneous. Twin and family-genetic studies provide evidence for strong genetic
components. An international consortium using an affected sib pair strategy has found a
promising linkage to a region on chromosome 7. In 10 to 15% of cases autism is due to
associated medical conditions that affect normal brain functioning. Postmortem studies on
small case series report cellular abnormalities in the limbic system and cerebellum.
Between 10 and 20% of individuals with autism have macrocephalia, which is in
accordance with magnetic resonance imaging (MRI) findings of an increased total brain
tissue volume and enlargement most prominent in the occipital and parietal lobes. The
most robust and well replicated neurobiological abnormality in autism is an elevation of
whole blood serotonin (5-hydroxytryptamine; 5-HT) found in over 30% of patients.
Pharmacological interventions with serotonin reuptake inhibitors or with atypical
neuroleptics that block both dopamine (D2) and serotonin (5-HT2) receptors seem to offer
clinical benefit and merit further study
861. Buitelaar JK, Van der Gaag R, Klin A, Volkmar F. Exploring the boundaries of Pervasive
Developmentl Disorder Not Otherwise Specified: Analyses from the DSM-IV Autistic
Disorder field trial. J Autism Dev Disord 1999;29(1):33-43.
Ref ID: 2716
Abstract: This study aimed to explore the boundaries between PDD and related disorders
and to develop classificatory algorithms for what is currently called Pervasive
Developmental Disorder Not Otherwise Specified (PDDNOS). Data collected by means of a
standard coding system for the DSM-IV field trial for autistic disorder were used.
Information on diagnostic criteria for autistic disorder as listed in ICD-10 and DSM-IV was
compared between subjects functioning at least in the mildly retarded range and clinically
216
classified as autistic disorder (n = 205), PDDNOS (n = 80) and other non-PDD disorders (n
= 174). Only a limited number of items from the ICD-10 and DSM-IV systems for autistic
disorder significantly discriminated the PDDNOS group from other disorders. A scoring rule
based on a short set of 7 ICD-10/DSM-IV criteria with a cutoff of 3 items and 1 social
interaction item set as mandatory had the best balance between high sensitivity and high
specificity in discriminating PDDNOS from non-PDD disorders. These rules yielded a
somewhat better prediction than most effective rules based on the full set of 12 criteria for
autistic disorder with a cutoff of 4 items and 1 social item as mandatory. Generally
accepted and well-validated criteria to identify individuals with PDDNOS should facilitate
both research and clinical services
862. Buitelaar JK, van der WM, Swaab-Barneveld H, van der Gaag RJ. Theory of mind and
emotion-recognition functioning in autistic spectrum disorders and in psychiatric control and
normal children. Dev Psychopathol 1999;11(1):39-58.
Ref ID: 4424
Abstract: The hypothesis was tested that weak theory of mind (ToM) and/or emotion
recognition (ER) abilities are specific to subjects with autism. Differences in ToM and ER
performance were examined between autistic (n = 20), pervasive developmental
disorder-not otherwise specified (PDD-NOS) (n = 20), psychiatric control (n = 20), and
normal children (n = 20). The clinical groups were matched person-to-person on age and
verbal IQ. We used tasks for the matching and the context recognition of emotional
expressions, and a set of first- and second-order ToM tasks. Autistic and PDD-NOS
children could not be significantly differentiated from each other, nor could they be
differentiated from the psychiatric controls with a diagnosis of ADHD (n = 9). The
psychiatric controls with conduct disorder or dysthymia performed about as well as normal
children. The variance in second-order ToM performance contributed most to differences
between diagnostic groups
863. Buitelaar JK, van der Gaag RJ, van der Hoeven J. Buspirone in the management of anxiety
and irritability in children with pervasive developmental disorders: results of an open-label
study. Journal of Clinical Psychiatry 1998;59(2):56-59.
Ref ID: 2470
Abstract: BACKGROUND: We evaluated the efficacy and safety of buspirone in the
management of anxiety and irritability in children with pervasive developmental disorders
(PDD). METHOD: Twenty-two subjects, 6 to 17 years old, with DSM-III-R diagnosed
PDD-NOS (N = 20) or autistic disorder (N = 2), were included. They were treated with
buspirone in dosages ranging from 15 to 45 mg/day in an open-label trial lasting 6 to 8
weeks. Responders continued buspirone treatment and were followed up for up to 12
months. RESULTS: Nine subjects had a marked therapeutic response and 7 subjects a
moderate response on the Clinical Global Impressions (CGI) scale after 6 to 8 weeks of
treatment. Side effects were minimal, except for 1 patient who developed abnormal
involuntary movements. CONCLUSION: These results suggest that buspirone may be
useful for treating symptoms of anxiety and irritability in children with PDD
864. Buitelaar JK, Dekker ME, van Ree JM, van Engeland H. A controlled trial with ORG 2766,
an ACTH-(4-9) analog, in 50 relatively able children with autism. European
Neuropsychopharmacology 1996;6(1):13-19.
Ref ID: 2195
Abstract: The aim of the present study was to replicate earlier findings of beneficial effects
of ORG 2766, an ACTH-(4-9) analog, in autistic children. Fifty children with autism, 7-15
years old and with a Performance IQ of more than 60, participated in a double-blind
placebo controlled parallel trial. Active treatment was 40 mg ORG 2766 for 6 weeks. The
outcome was assessed on the basis of the Aberrant Behavior Checklist completed by
parents and teachers, and by means of a detailed behavioral observation (30 subjects).
ORG 2766 failed to improve social and communicative behavior at a group level. The rate
of individual response, defined as a reliable change in social withdrawal at home and at
217
school, to ORG 2766 (10 out of 30) and placebo (4 out of 20) was not significant either. The
children who responded to ORG 2766, but not those who responded to placebo,
manifested significant improvements outside the changes in the defining variables,
including a decrease in hyperactivity at school. The responders to ORG 2766 were
characterized mainly by a relatively lower PIQ; further by more initial hyperactivity,
stereotypies and abnormal speech, and less initial eye contact. The responders to placebo
could not be differentiated from the non-responders to placebo. Future studies should
examine whether ORG 2766 differentially affects various subtypes of autism
865. Bukelis I, Porter FD, Zimmerman AW, Tierney E. Smith-Lemli-Opitz syndrome and autism
spectrum disorder. Am J Psychiatry 2007;164(11):1655-1661.
Ref ID: 5561
866. Bulman-Fleming MB, Bryden MP. Simultaneous verbal and affective laterality effects.
Neuropsychologia 1994;32(7):787-797.
Ref ID: 2790
Abstract: By analyzing the error scores of normal participants asked to identify a specific
word spoken in a specific tone of voice (for example, the word "tower" spoken in a happy
tone of voice), we have been able to demonstrate concurrent verbal and affective cerebral
laterality effects in a dichotic listening task. The targets comprised the 16 possible
combinations of four two-syllable words spoken in four different tones of voice. There were
128 participants equally divided between left- and right-handers, with equal numbers of
each sex within each handedness group. Each participant responded to 144 trials on the
dichotic task, and filled in the 32-item Waterloo Handedness Questionnaire. Analysis of
false positive responses on the dichotic task (responding "yes" when only the verbal or only
the affective component of the target was present, or when both components were present
but were at opposite ears) indicated that significantly more errors were made when the
verbal aspect of the target appeared at the right ear (left hemisphere) and the emotional
aspect was at the left ear (right hemisphere) than when the reverse was the case. A single
task has generated both effects, so that differences in participants' strategies or the way in
which attention is biased cannot account for the results. While the majority of participants
showed a right-ear advantage for verbal material and a left-ear advantage for nonverbal
material, these two effects were not correlated, suggesting that independent mechanisms
probably underly the establishment of verbal and affective processing. We found no
significant sex or handedness effects, though left-handers were much more variable than
were right-handers. There were no significant correlations between degree of handedness
as measured on the handedness questionnaire and extent of lateralization of verbal or
affective processing on the dichotic task. We believe that this general technique may be
able to provide information as to the nature and extent of interhemispheric integration of
information, and is easily adaptable to other modalities, thus holds great promise for future
research
867. Buoni S, Sorrentino L, Farnetani MA, Pucci L, Fois A. The syndrome of inv dup (15):
clinical, electroencephalographic, and imaging findings. J Child Neurol 2000;15(6):380-385.
Ref ID: 3485
Abstract: The clinical and laboratory data of four pediatric patients and one adult patient
with inverted duplication (inv dup) (15) are reported. The most evident findings were
dysmorphic features with frontal bossing; genital abnormalities, such as macropenis or
hypospadias; mental retardation; autistic behavior; and seizures. Two additional adults with
inv dup (15) from other institutions were also diagnosed in our laboratory. Seizures and
mental retardation were the reasons for their referral. The clinical picture of inv dup (15)
seems to be quite variable since the phenotype can also be normal. However, karyotyping
and fluorescent in-situ hybridization, focused in particular on chromosome 15, appear to be
indicated in patients with dysmorphic phenotypes, such as the one present in our patients,
and in subjects with early-onset seizures and psychomotor retardation with autistic features
218
868. Buonomano DV, Merzenich MM. Cortical plasticity: from synapses to maps. Annual Review
of Neuroscience 1998;21:149-186.
Ref ID: 2757
Abstract: It has been clear for almost two decades that cortical representations in adult
animals are not fixed entities, but rather, are dynamic and are continuously modified by
experience. The cortex can preferentially allocate area to represent the particular peripheral
input sources that are proportionally most used. Alterations in cortical representations
appear to underlie learning tasks dependent on the use of the behaviorally important
peripheral inputs that they represent. The rules governing this cortical representational
plasticity following manipulations of inputs, including learning, are increasingly well
understood. In parallel with developments in the field of cortical map plasticity, studies of
synaptic plasticity have characterized specific elementary forms of plasticity, including
associative long-term potentiation and long-term depression of excitatory postsynaptic
potentials. Investigators have made many important strides toward understanding the
molecular underpinnings of these fundamental plasticity processes and toward defining the
learning rules that govern their induction. The fields of cortical synaptic plasticity and
cortical map plasticity have been implicitly linked by the hypothesis that synaptic plasticity
underlies cortical map reorganization. Recent experimental and theoretical work has
provided increasingly stronger support for this hypothesis. The goal of the current paper is
to review the fields of both synaptic and cortical map plasticity with an emphasis on the
work that attempts to unite both fields. A second objective is to highlight the gaps in our
understanding of synaptic and cellular mechanisms underlying cortical representational
plasticity. [References: 191]
869. Burack JA, Enns JT, Stauder JEA, Mottron L, Randolph B. Attention and autism: behavioral
and electrophysiological evidence. In: Cohen DJ, Volkmar FR, editors. Autism and
pervasive developmental disorders. 2 ed. New York: John Wiley & Sons; 1997:226-247.
Ref ID: 2919
870. Burack JA, Volkmar FR. Development of low- and high-functioning autistic children. J Child
Psychol Psychiatry 1992;33:607-616.
Ref ID: 214
871. Buratowski S. DNA repair and transcription: the helicase connection. Science
1993;260(5104):37-38.
Ref ID: 5765
872. Burd L, Fisher W, Kerbeshian J. Pervasive disintegrative disorder: Are Rett syndrome and
Heller dementia infantilis subtypes? Dev Med Child Neurol 1989;31:609-616.
Ref ID: 232
873. Burd L, Fisher W, Kerbeshian J, Arnold M. Is development of Tourette disorder a marker for
improvement in patients with autism and other pervasive development disorders? J Am
Acad Child Adolesc Psychiatry 1987;26:162-165.
Ref ID: 937
874. Burd L, Fisher W, Knowlton D, Kerbeshian J. Hyperlexia: A marker for improvement in
children with pervasive developmental disorder? J Am Acad Child Psychiatry
1987;26(3):407-412.
Ref ID: 935
875. Burger RA, Warren RP. Possible immunogenetic basis for autism. MRDDRR
1998;4(2):137-141.
Ref ID: 2110
219
876. Burgess NK, Sweeten TL, McMahon WM, Fujinami RS. Hyperserotoninemia and altered
immunity in autism. J Autism Dev Disord 2006;36(5):697-704.
Ref ID: 4912
Abstract: One of the most consistent biological findings in autism is elevated whole blood
serotonin (5-HT) levels found in about 1/3 of cases. Immune abnormalities are also
commonly observed in this disorder. Given 5-HT's role as an immunomodulator, possible
connections between 5-HT and immune abnormalities in autism are explored in this review.
Areas of focus include hyperserotoninemia and cellular immune function, autoantibodies to
5-HT receptors, and 5-HT's role in autoimmunity. Further research is needed to determine
the interactions between neuropsychiatric and immune dysfunction in autism and related
disorders
877. Burgio-Murphy A, Klorman R, Shaywitz SE et al. Error-related event-related potentials in
children with attention-deficit hyperactivity disorder, oppositional defiant disorder, reading
disorder, and math disorder. Biol Psychol 2007;75(1):75-86.
Ref ID: 7221
Abstract: We studied error-related negativity (ERN) and error positivity (Pe) during a
discrimination task in 319 unmedicated children divided into subtypes of ADHD
(Not-ADHD/inattentive/combined), learning disorder (Not-LD/reading/math/reading+math),
and oppositional defiant disorder. Response-locked ERPs contained a frontocentral ERN
and posterior Pe. Error-related negativity and positivity exhibited larger amplitude and later
latency than corresponding waves for correct responses matched on reaction time. ADHD
did not affect performance on the task. The ADHD/combined sample exceeded controls in
ERN amplitude, perhaps reflecting patients' adaptive monitoring efforts. Compared with
controls, subjects with reading disorder and reading+math disorder performed worse on the
task and had marginally more negative correct-related negativities. In contrast, Pe/Pc was
smaller in children with reading+math disorder than among subjects with reading disorder
and Not-LD participants; this nonspecific finding is not attributable to error processing. The
results reflect anomalies in error processing in these disorders but further research is
needed to address inconsistencies in the literature
878. Buschman TJ, Miller EK. Top-down versus bottom-up control of attention in the prefrontal
and posterior parietal cortices. Science 2007;315(5820):1860-1862.
Ref ID: 5031
Abstract: Attention can be focused volitionally by "top-down" signals derived from task
demands and automatically by "bottom-up" signals from salient stimuli. The frontal and
parietal cortices are involved, but their neural activity has not been directly compared.
Therefore, we recorded from them simultaneously in monkeys. Prefrontal neurons reflected
the target location first during top-down attention, whereas parietal neurons signaled it
earlier during bottom-up attention. Synchrony between frontal and parietal areas was
stronger in lower frequencies during top-down attention and in higher frequencies during
bottom-up attention. This result indicates that top-down and bottom-up signals arise from
the frontal and sensory cortex, respectively, and different modes of attention may
emphasize synchrony at different frequencies
879. Butler MG. Prader-Willi Syndrome: Obesity due to Genomic Imprinting. Curr Genomics
2011;12(3):204-215.
Ref ID: 7427
Abstract: Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder due to
errors in genomic imprinting with loss of imprinted genes that are paternally expressed from
the chromosome 15q11-q13 region. Approximately 70% of individuals with PWS have a de
novo deletion of the paternally derived 15q11-q13 region in which there are two subtypes
(i.e., larger Type I or smaller Type II), maternal disomy 15 (both 15s from the mother) in
about 25% of cases, and the remaining subjects have either defects in the imprinting center
controlling the activity of imprinted genes or due to other chromosome 15 rearrangements.
PWS is characterized by a particular facial appearance, infantile hypotonia, a poor suck
220
and feeding difficulties, hypogonadism and hypogenitalism in both sexes, short stature and
small hands and feet due to growth hormone deficiency, mild learning and behavioral
problems (e.g., skin picking, temper tantrums) and hyperphagia leading to early childhood
obesity. Obesity is a significant health problem, if uncontrolled. PWS is considered the most
common known genetic cause of morbid obesity in children. The chromosome 15q11-q13
region contains approximately 100 genes and transcripts in which about 10 are imprinted
and paternally expressed. This region can be divided into four groups: 1) a proximal
non-imprinted region; 2) a PWS paternal-only expressed region containing protein-coding
and non-coding genes; 3) an Angelman syndrome region containing maternally expressed
genes and 4) a distal non-imprinted region. This review summarizes the current
understanding of the genetic causes, the natural history and clinical presentation of
individuals with PWS
880. Butler MG, Dasouki MJ, Zhou XP et al. Subset of individuals with autism spectrum
disorders and extreme macrocephaly associated with germline PTEN tumour suppressor
gene mutations. J Med Genet 2005;42(4):318-321.
Ref ID: 6481
Abstract: The genetic aetiology of autism remains elusive. Occasionally, individuals with
Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as
Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are
characterised by germline PTEN mutations, and may have neurobehavioural features
resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook
PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism
spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five
females; ages 3.1-18.4 years) with a head circumference range from 2.5 to 8.0 standard
deviations above the mean, three males (17%) carried germline PTEN mutations. These
three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon
7), and F241S (exon 7). They had the larger head circumference measurements amongst
all our study subjects. The three residues altered in our patients were highly evolutionarily
conserved. We suggest that PTEN gene testing be considered for patients with autistic
behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks
as well as medical management for the patient
881. Butterworth B, Kovas Y. Understanding neurocognitive developmental disorders can
improve education for all. Science 2013;340(6130):300-305.
Ref ID: 7577
Abstract: Specific learning disabilities (SLDs) are estimated to affect up to 10% of the
population, and they co-occur far more often than would be expected, given their
prevalences. We need to understand the complex etiology of SLDs and their
co-occurrences in order to underpin the training of teachers, school psychologists, and
clinicians, so that they can reliably recognize SLDs and optimize the learning contexts for
individual learners
882. Butterworth B, Varma S, Laurillard D. Dyscalculia: from brain to education. Science
2011;332(6033):1049-1053.
Ref ID: 7338
Abstract: Recent research in cognitive and developmental neuroscience is providing a new
approach to the understanding of dyscalculia that emphasizes a core deficit in
understanding sets and their numerosities, which is fundamental to all aspects of
elementary school mathematics. The neural bases of numerosity processing have been
investigated in structural and functional neuroimaging studies of adults and children, and
neural markers of its impairment in dyscalculia have been identified. New interventions to
strengthen numerosity processing, including adaptive software, promise effective
evidence-based education for dyscalculic learners
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883. Butterworth B. Foundational numerical capacities and the origins of dyscalculia. Trends
Cogn Sci 2010;14(12):534-541.
Ref ID: 7339
Abstract: One important cause of very low attainment in arithmetic (dyscalculia) seems to
be a core deficit in an inherited foundational capacity for numbers. According to one set of
hypotheses, arithmetic ability is built on an inherited system responsible for representing
approximate numerosity. One account holds that this is supported by a system for
representing exactly a small number (less than or equal to four4) of individual objects. In
these approaches, the core deficit in dyscalculia lies in either of these systems. An
alternative proposal holds that the deficit lies in an inherited system for sets of objects and
operations on them (numerosity coding) on which arithmetic is built. I argue that a deficit in
numerosity coding, not in the approximate number system or the small number system, is
responsible for dyscalculia. Nevertheless, critical tests should involve both longitudinal
studies and intervention, and these have yet to be carried out
884. Butterworth B. The development of arithmetical abilities. J Child Psychol Psychiatry
2005;46(1):3-18.
Ref ID: 7450
Abstract: BACKGROUND: Arithmetical skills are essential to the effective exercise of
citizenship in a numerate society. How these skills are acquired, or fail to be acquired, is of
great importance not only to individual children but to the organisation of formal education
and its role in society. METHOD: The evidence on the normal and abnormal developmental
progression of arithmetical abilities is reviewed; in particular, evidence for arithmetical
ability arising from innate specific cognitive skills (innate numerosity) vs. general cognitive
abilities (the Piagetian view) is compared. RESULTS: These include evidence from infancy
research, neuropsychological studies of developmental dyscalculia, neuroimaging and
genetics. The development of arithmetical abilities can be described in terms of the idea of
numerosity -- the number of objects in a set. Early arithmetic is usually thought of as the
effects on numerosity of operations on sets such as set union. The child's concept of
numerosity appears to be innate, as infants, even in the first week of life, seem to
discriminate visual arrays on the basis of numerosity. Development can be seen in terms of
an increasingly sophisticated understanding of numerosity and its implications, and in
increasing skill in manipulating numerosities. The impairment in the capacity to learn
arithmetic -- dyscalculia -- can be interpreted in many cases as a deficit in the concept in
the child's concept of numerosity. The neuroanatomical bases of arithmetical development
and other outstanding issues are discussed. CONCLUSIONS: The evidence broadly
supports the idea of an innate specific capacity for acquiring arithmetical skills, but the
effects of the content of learning, and the timing of learning in the course of development,
requires further investigation
885. Buxbaum JD, Hof PR. The emerging neuroscience of autism spectrum disorders. Brain
Res 2011;1380:1-2.
Ref ID: 7001
886. Buxbaum JD. Multiple rare variants in the etiology of autism spectrum disorders. Dialogues
Clin Neurosci 2009;11(1):35-43.
Ref ID: 6462
Abstract: Recent studies in autism spectrum disorders (ASDs) support an important role for
multiple rare variants in these conditions. This is a clinically important finding, as, with the
demonstration that a significant proportion of ASDs are the result of rare, etiological genetic
variants, it becomes possible to make use of genetic testing to supplement behavioral
analyses for an earlier diagnosis. As it appears that earlier interventions in ASDs will
produce better outcomes, the development of genetic testing to augment behaviorally
based evaluations in ASDs holds promise for improved treatment. Furthermore, these rare
variants involve synaptic and neuronal genes that implicate specific pathways, cells, and
subcellular compartments in ASDs, which in turn will suggest novel therapeutic approaches
222
in ASDs. Of particular recent interest are the synaptic cell adhesion and associated
molecules, including neurexin 1, neuroligin 3 and 4, and SHANK3, which implicate
glutamatergic synapse abnormalities in ASDs. In the current review we will overview the
evidence for a genetic etiology for ASDs, and summarize recent genetic findings in these
disorders
887. Buxbaum JD, Cai G, Chaste P et al. Mutation screening of the PTEN gene in patients with
autism spectrum disorders and macrocephaly. Am J Med Genet B Neuropsychiatr Genet
2007;144(4):484-491.
Ref ID: 5105
Abstract: Mutations in the PTEN gene are associated with a broad spectrum of disorders,
including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus
syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been
described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In
this study, we screened the PTEN gene for mutations and deletions in 88 patients with
ASDs and macrocephaly (defined as >or=2 SD above the mean). Mutation analysis was
performed by direct sequencing of all exons and flanking regions, as well as the promoter
region. Dosage analysis of PTEN was carried out using multiplex ligation-dependent probe
amplification (MLPA). No partial or whole gene deletions were observed. We identified a de
novo missense mutation (D326N) in a highly conserved amino acid in a 5-year-old boy with
autism, mental retardation, language delay, extreme macrocephaly (+9.6 SD) and
polydactyly of both feet. Polydactyly has previously been described in two patients with
Lhermitte-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations.
Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with
macrocephaly. Screening of PTEN mutations is warranted in patients with autism and
pronounced macrocephaly, even in the absence of other features of PTEN-related tumor
syndromes
888. Buxbaum JD, Cai G, Nygren G et al. Mutation analysis of the NSD1 gene in patients with
autism spectrum disorders and macrocephaly. BMC Med Genet 2007;8:68.
Ref ID: 6601
Abstract: BACKGROUND: Sotos syndrome is an overgrowth syndrome characterized by
macrocephaly, advanced bone age, characteristic facial features, and learning disabilities,
caused by mutations or deletions of the NSD1 gene, located at 5q35. Sotos syndrome has
been described in a number of patients with autism spectrum disorders, suggesting that
NSD1 could be involved in other cases of autism and macrocephaly. METHODS: We
screened the NSD1 gene for mutations and deletions in 88 patients with autism spectrum
disorders and macrocephaly (head circumference 2 standard deviations or more above the
mean). Mutation analysis was performed by direct sequencing of all exons and flanking
regions. Dosage analysis of NSD1 was carried out using multiplex ligation-dependent
probe amplification. RESULTS: We identified three missense variants (R604L, S822C and
E1499G) in one patient each, but none is within a functional domain. In addition,
segregation analysis showed that all variants were inherited from healthy parents and in
two cases were also present in unaffected siblings, indicating that they are probably
nonpathogenic. No partial or whole gene deletions/duplications were observed.
CONCLUSION: Our findings suggest that Sotos syndrome is a rare cause of autism
spectrum disorders and that screening for NSD1 mutations and deletions in patients with
autism and macrocephaly is not warranted in the absence of other features of Sotos
syndrome
889. Buxbaum JD, Silverman J, Keddache M et al. Linkage analysis for autism in a subset
families with obsessive-compulsive behaviors: evidence for an autism susceptibility gene
on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19.
Mol Psychiatry 2004;9(2):144-150.
Ref ID: 4223
Abstract: Although there is considerable evidence for a strong genetic component to
223
idiopathic autism, several genome-wide screens for susceptibility genes have been carried
out with limited concordance of linked loci, reflecting numerous genes of weak effect and/or
sample heterogeneity. In the current study, linkage analysis was carried out in a sample of
62 autism-affected relative pairs with more severe obsessive-compulsive behaviors,
selected from a larger (n=115) set of autism-affected relative pairs as a means of reducing
sample heterogeneity. Obsessive-compulsive behaviors were assessed using the Autism
Diagnostic Interview-Revised (ADI-R). In the sample with more severe
obsessive-compulsive behaviors, multipoint NPL scores above 2 were observed on
chromosomes 1, 4, 5, 6, 10, 11 and 19, with the strongest evidence for linkage on
chromosome 1 at the marker D1S1656, where the multipoint NPL score was 3.06, and the
two-point NPL score was 3.21. In follow-up analyses, analyzing the subset of families
(n=35) where the patients had the most severe obsessive-compulsive behaviors generated
a multipoint NPL score of 2.76, and a two-point NPL score of 2.79, indicating that the bulk
of evidence for linkage was derived from the families most severely affected with
obsessive-compulsive behaviors. The data suggest that there is an autism susceptibility
gene on chromosome 1 and provide further support for the presence of autism
susceptibility genes on chromosomes 6 and 19
890. Buxbaum JD, Silverman JM, Smith CJ et al. Evidence for a susceptibility gene for autism
on chromosome 2 and for genetic heterogeneity. Am J Hum Genet 2001;68(6):1514-1520.
Ref ID: 3541
Abstract: Although there is considerable evidence for a strong genetic component to
idiopathic autism, several genomewide screens for susceptibility genes have been
performed with limited concordance of linked loci, reflecting either numerous genes of weak
effect and/or sample heterogeneity. Because decreasing sample heterogeneity would
increase the power to identify genes, the effect on evidence for linkage of restricting a
sample of autism-affected relative pairs to those with delayed onset (at age >36 mo) of
phrase speech (PSD, for phrase speech delay) was studied. In the second stage of a
two-stage genome screen for susceptibility loci involving 95 families with two or more
individuals with autism or related disorders, a maximal multipoint heterogeneity LOD score
(HLOD) of 1.96 and a maximal multipoint nonparametric linkage (NPL) score of 2.39 was
seen on chromosome 2q. Restricting the analysis to the subset of families (n=49) with two
or more individuals having a narrow diagnosis of autism and PSD generated a maximal
multipoint HLOD score of 2.99 and an NPL score of 3.32. The increased scores in the
restricted sample, together with evidence for heterogeneity in the entire sample, indicate
that the restricted sample comprises a population that is more genetically homogeneous,
which could therefore increase the likelihood of positional cloning of susceptibility loci
891. Buxhoeveden D, Roy E, Switala A, Casanova MF. Reduced interneuronal space in
schizophernia. Biol Psychiatry 2000;47(7):681-683.
Ref ID: 3549
892. Buxhoeveden DP, Semendeferi K, Buckwalter J, Schenker N, Switzer R, Courchesne E.
Reduced minicolumns in the frontal cortex of patients with autism. Neuropathol Appl
Neurobiol 2006;32(5):483-491.
Ref ID: 5168
Abstract: Cell minicolumns were shown to be narrower in frontal regions in brains of autistic
patients compared with controls. This was not found in primary visual cortex. Within the
frontal cortex, dorsal and orbital regions displayed the greatest differences while the mesial
region showed the least change. We also found that minicolumns in the brain of a
3-year-old autistic child were indistinguishable from those of the autistic adult in two of
three frontal regions, in contrast to the control brains. This may have been due to the small
size of the columns in the adult autistic brain rather than to an accelerated development.
The presence of narrower minicolumns supports the theory that there is an abnormal
increase in the number of ontogenetic column units produced in some regions of the
autistic brain during corticoneurogenesis
224
893. Buxhoeveden DP, Casanova MF. The minicolumn hypothesis in neuroscience. Brain
2002;125(Pt 5):935-951.
Ref ID: 3667
Abstract: The minicolumn is a continuing source of research and debate more than half a
century after it was identified as a component of brain organization. The minicolumn is a
sophisticated local network that contains within it the elements for redundancy and
plasticity. Although it is sometimes compared to subcortical nuclei, the design of the
minicolumn is a distinctive form of module that has evolved specifically in the neocortex. It
unites the horizontal and vertical components of cortex within the same cortical space.
Minicolumns are often considered highly repetitive, even clone-like, units. However, they
display considerable heterogeneity between areas and species, perhaps even within a
given macrocolumn. Despite a growing recognition of the anatomical basis of the cortical
minicolumn, as well as its physiological properties, the potential of the minicolumn has not
been exploited in fields such as comparative neuroanatomy, abnormalities of the brain and
mind, and evolution
894. Buxhoeveden DP, Switala AE, Roy E, Casanova MF. Quantitative analysis of cell columns
in the cerebral cortex. J Neurosci Methods 2000;97(1):7-17.
Ref ID: 3550
Abstract: We present a quantified imaging method that describes the cell column in
mammalian cortex. The minicolumn is an ideal template with which to examine cortical
organization because it is a basic unit of function, complete in itself, which interacts with
adjacent and distance columns to form more complex levels of organization. The subtle
details of columnar anatomy should reflect physiological changes that have occurred in
evolution as well as those that might be caused by pathologies in the brain. In this
semiautomatic method, images of Nissl- stained tissue are digitized or scanned into a
computer imaging system. The software detects the presence of cell columns and
describes details of their morphology and of the surrounding space. Columns are detected
automatically on the basis of cell-poor and cell-rich areas using a Gaussian distribution. A
line is fit to the cell centers by least squares analysis. The line becomes the center of the
column from which the precise location of every cell can be measured. On this basis
several algorithms describe the distribution of cells from the center line and in relation to
the available surrounding space. Other algorithms use cluster analyses to determine the
spatial orientation of every column
895. Cabanlit M, Wills S, Goines P, Ashwood P, Van de WJ. Brain-specific autoantibodies in the
plasma of subjects with autistic spectrum disorder. Ann N Y Acad Sci 2007;1107:92-103.
Ref ID: 5464
Abstract: Although autism spectrum disorder (ASD) is diagnosed on the basis of behavioral
parameters, several studies have reported immune system abnormalities and suggest the
possible role of autoimmunity in the pathogenesis of ASD. In this study we sought to
assess the incidence of brain-specific autoantibodies in the plasma of children with autism
(AU) compared to age-matched controls including, siblings without ASD, typically
developing (TD) controls, and children with other developmental disabilities, but not autism
(DD). Plasma from 172 individuals (AU, n = 63, median age: 43 months; TD controls, n =
63, median age: 48 months; siblings, n = 25, median age: 61 months; and DD controls, n =
21, median age: 38 months) was analyzed by Western blot for the presence of IgG
antibodies against protein extracts from specific regions of the human adult brain including
the hypothalamus and thalamus. The presence of a approximately 52 kDa MW band, in the
plasma of subjects with AU, was detected with a significantly higher incidence when
compared to plasma from TD controls (29% vs. 8%, P = 0.0027 and 30% vs. 11%, P =
0.01, in the thalamus and hypothalamus, respectively). Reactivity to three brain proteins
(42-48 kDa MW), in particular in the hypothalamus, were observed with increased
incidence in 37% of subjects with AU compared to 13% TD controls (P = 0.004). Multiple
brain-specific autoantibodies are present at significantly higher frequency in children with
AU. While the potential role of these autoantibodies in AU is currently unknown, their
225
presence suggests a loss of self-tolerance to one or more neural antigens during early
childhood
896. Cabeza R, Nyberg L. Imaging cognition II: An empirical review of 275 PET and fMRI
studies. J Cogn Neurosci 2000;12(1):1-47.
Ref ID: 7541
Abstract: Positron emission tomography (PET) and functional magnetic resonance imaging
(fMRI) have been extensively used to explore the functional neuroanatomy of cognitive
functions. Here we review 275 PET and fMRI studies of attention (sustained, selective,
Stroop, orientation, divided), perception (object, face, space/motion, smell), imagery
(object, space/motion), language (written/spoken word recognition, spoken/no spoken
response), working memory (verbal/numeric, object, spatial, problem solving), semantic
memory retrieval (categorization, generation), episodic memory encoding (verbal, object,
spatial), episodic memory retrieval (verbal, nonverbal, success, effort, mode, context),
priming (perceptual, conceptual), and procedural memory (conditioning, motor, and
nonmotor skill learning). To identify consistent activation patterns associated with these
cognitive operations, data from 412 contrasts were summarized at the level of cortical
Brodmann's areas, insula, thalamus, medial-temporal lobe (including hippocampus), basal
ganglia, and cerebellum. For perception and imagery, activation patterns included primary
and secondary regions in the dorsal and ventral pathways. For attention and working
memory, activations were usually found in prefrontal and parietal regions. For language
and semantic memory retrieval, typical regions included left prefrontal and temporal
regions. For episodic memory encoding, consistently activated regions included left
prefrontal and medial temporal regions. For episodic memory retrieval, activation patterns
included prefrontal, medial temporal, and posterior midline regions. For priming,
deactivations in prefrontal (conceptual) or extrastriate (perceptual) regions were
consistently seen. For procedural memory, activations were found in motor as well as in
non-motor brain areas. Analysis of regional activations across cognitive domains suggested
that several brain regions, including the cerebellum, are engaged by a variety of cognitive
challenges. These observations are discussed in relation to functional specialization as well
as functional integration
897. Cacace AT, McFarland DJ. The importance of modality specificity in diagnosing central
auditory processing disorder. Am J Audiol 2005;14(2):112-123.
Ref ID: 5442
Abstract: PURPOSE: This article argues for the use of modality specificity as a unifying
framework by which to conceptualize and diagnose central auditory processing disorder
(CAPD). The intent is to generate dialogue and critical discussion in this area of study.
METHOD: Research in the cognitive, behavioral, and neural sciences that relates to the
concept of modality specificity was reviewed and synthesized. RESULTS: Modality
specificity has a long history as an organizing construct within a diverse collection of
mainstream scientific disciplines. The principle of modality specificity was contrasted with
the unimodal inclusive framework, which holds that auditory tests alone are sufficient to
make the CAPD diagnosis. Evidence from a large body of data demonstrated that the
unimodal framework was unable to delineate modality-specific processes from more
generalized dysfunction; it lacked discriminant validity and resulted in an incomplete
assessment. Consequently, any hypothetical model resulting from incomplete assessments
or potential therapies that are based on indeterminate diagnoses are themselves
questionable, and caution should be used in their application. CONCLUSIONS: Improving
specificity of diagnosis is an imperative core issue to the area of CAPD. Without specificity,
the concept has little explanatory power. Because of serious flaws in concept and design,
the unimodal inclusive framework should be abandoned in favor of a more valid approach
that uses modality specificity
898. Cacace AT, McFarland DJ. Central auditory processing disorder in school-aged children: a
critical review. Journal of Speech, Language, & Hearing Research 1998;41(2):355-373.
226
Ref ID: 2581
Abstract: The rationale to evaluate for central auditory processing disorder (CAPD) in
school-aged children is based on the assumption that an auditory-specific perceptual deficit
underlies many learning problems including specific reading and language disabilities. A
fundamental issue in this area is whether convincing empirical evidence exists to validate
this proposition. Herein, we consider the issue of modality specificity by examining the
extent to which reading, language, and attention disorders in school-aged children involve
perceptual dysfunctions limited to a single sensory modality. Difficulty in validating CAPD
as a diagnostic label is due in large part to use of the unimodal inclusive framework, which
has biased the diagnosis to favor sensitivity of test results over documenting the specificity
of the deficit. Indeed, empirical research documenting modality-specific auditory-perceptual
dysfunction in this population is scarce. Therefore, the existing literature on this topic has
not clarified the "true" nature of the problem, and has left many questions about this
disorder unanswered. It is argued that demonstrating modality specificity is one way to rule
out supramodal disorders as explanations for observed dysfunction. Multimodal perceptual
testing is one logical approach to help clarify this area of investigation. [References: 222]
899. Caggana M, Kilgallen J, Conroy JM et al. Associations between ERCC2 polymorphisms
and gliomas. Cancer Epidemiol Biomarkers Prev 2001;10(4):355-360.
Ref ID: 3741
Abstract: Xeroderma pigmentosum complementation group D/excision repair
cross-complementing in rodents 2 (ERCC2) encodes a protein that is part of the nucleotide
excision repair pathway and the transcription factor IIH transcription complex. Mutations in
this gene have been shown to cause three distinct clinical diseases including xeroderma
pigmentosum, Cockayne syndrome, and trichothiodystrophy. Several ERCC2
polymorphisms, the effects of which on gene function are not known, have been described.
To investigate whether constitutive sequence variations might be associated with adult
onset gliomas, blood specimens from a case-control study (187 cases and 169 controls)
were genotyped for seven previously described polymorphisms (R156R, I199M, H201Y,
D312N, A575A, D711D, and K751Q). A novel R616C polymorphism was also identified.
Cases were significantly more likely than controls to be homozygous for the silent AA
variant at codon 156 (odds ratio, 2.3; 95% confidence interval, 1.3-4.2). Although this was
observed for patients in each of three histological subgroups of cases, (glioblastoma
multiforme, astrocytoma, and oligoastrocytoma) compared with controls, the association
was strongest for patients with oligoastrocytoma (odds ratio, 3.2; 95% confidence interval,
1.1-9.5). In contrast, cases were somewhat less likely than controls to carry variants at
D312N, D711D, and K751Q, but not significantly so overall or for any subgroup after
adjustment for age and gender. Individuals with variant nucleotides at D312N, D711D, and
K751Q were significantly more likely to carry a variant at another of those three codons and
less likely to carry a variant nucleotide at R156R, regardless of case or control status.
Although the pattern of association observed here is consistent with a role of ERCC2
variants in the prevention or causation of glioma, these results are also consistent with the
possibility that another gene linked to ERCC2 may be involved. This seems especially so
because the strongest association was observed with a silent nucleotide variation
900. Caglayan AO. Genetic causes of syndromic and non-syndromic autism. Dev Med Child
Neurol 2010;52:130-138.
Ref ID: 6461
Abstract: Aims Over the past decade, genetic tests have become available for numerous
heritable disorders, especially those whose inheritance follows the Mendelian model.
Autism spectrum disorders (ASDs) represent a group of developmental disorders with a
strong genetic basis. During the past few years, genetic research in ASDs has been
successful in identifying several vulnerability loci and a few cytogenetic abnormalities or
single-base mutations implicated in the causation of autism. Method In this study the
literature was reviewed to highlight genotype-phenotype correlations between causal gene
mutations or cytogenetic abnormalities and behavioural or morphological phenotypes.
227
Results Based on this knowledge, practical information is offered to help clinicians pursue
targeted genetic testing of individuals with autism whose clinical phenotype is suggestive of
a specific genetic or genomic aetiology. Interpretation Comprehensive research into the
molecular mechanism of autism is required to aid the development of disease-specific
targeted therapies. In order to transfer this recently acquired knowledge into clinical
practice, it is critical to define a set of phenotypic inclusion criteria that must be met by
affected probands to justify their enrolment in a specific genetic testing programme
901. Cai G, Edelmann L, Goldsmith JE et al. Multiplex ligation-dependent probe amplification for
genetic screening in autism spectrum disorders: efficient identification of known
microduplications and identification of a novel microduplication in ASMT. BMC Med
Genomics 2008;1:50.
Ref ID: 6521
Abstract: BACKGROUND: It has previously been shown that specific microdeletions and
microduplications, many of which also associated with cognitive impairment (CI), can
present with autism spectrum disorders (ASDs). Multiplex ligation-dependent probe
amplification (MLPA) represents an efficient method to screen for such recurrent
microdeletions and microduplications. METHODS: In the current study, a total of 279
unrelated subjects ascertained for ASDs were screened for genomic disorders associated
with CI using MLPA. Fluorescence in situ hybridization (FISH), quantitative polymerase
chain reaction (Q-PCR) and/or direct DNA sequencing were used to validate potential
microdeletions and microduplications. Methylation-sensitive MLPA was used to
characterize individuals with duplications in the Prader-Willi/Angelman (PWA) region.
RESULTS: MLPA showed two subjects with typical ASD-associated interstitial duplications
of the 15q11-q13 PWA region of maternal origin. Two additional subjects showed smaller,
de novo duplications of the PWA region that had not been previously characterized. Genes
in these two novel duplications include GABRB3 and ATP10A in one case, and MKRN3,
MAGEL2 and NDN in the other. In addition, two subjects showed duplications of the
22q11/DiGeorge syndrome region. One individual was found to carry a 12 kb deletion in
one copy of the ASPA gene on 17p13, which when mutated in both alleles leads to
Canavan disease. Two subjects showed partial duplication of the TM4SF2 gene on Xp11.4,
previously implicated in X-linked non-specific mental retardation, but in our subsequent
analyses such variants were also found in controls. A partial duplication in the ASMT gene,
located in the pseudoautosomal region 1 (PAR1) of the sex chromosomes and previously
suggested to be involved in ASD susceptibility, was observed in 6-7% of the cases but in
only 2% of controls (P = 0.003). CONCLUSION: MLPA proves to be an efficient method to
screen for chromosomal abnormalities. We identified duplications in 15q11-q13 and in
22q11, including new de novo small duplications, as likely contributing to ASD in the
current sample by increasing liability and/or exacerbating symptoms. Our data indicate that
duplications in TM4SF2 are not associated with the phenotype given their presence in
controls. The results in PAR1/PAR2 are the first large-scale studies of gene dosage in
these regions, and the findings at the ASMT locus indicate that further studies of the
duplication of the ASMT gene are needed in order to gain insight into its potential
involvement in ASD. Our studies also identify some limitations of MLPA, where single base
changes in probe binding sequences alter results. In summary, our studies indicate that
MLPA, with a focus on accepted medical genetic conditions, may be an inexpensive
method for detection of microdeletions and microduplications in ASD patients for purposes
of genetic counselling if MLPA-identified deletions are validated by additional methods
902. Cairns NJ, Neumann M, Bigio EH et al. TDP-43 in familial and sporadic frontotemporal
lobar degeneration with ubiquitin inclusions. Am J Pathol 2007;171(1):227-240.
Ref ID: 5814
Abstract: TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic
and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative
inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a
novel class of neurodegenerative diseases called TDP-43 proteinopathies. We performed
228
ubiquitin and TDP-43 immunohistochemistry on 193 cases of familial and sporadic FTLD
with or without MND. On selected cases, immunoelectron microscopy and biochemistry
were performed. Clinically defined frontotemporal dementias (FTDs) included four groups:
1) familial FTD with mutations in progranulin (n = 36), valosin-containing protein (n = 5),
charged multivesicular body protein 2B (n = 4), and linked to chromosome 9p (n = 7); 2)
familial cases of FTD with unknown gene association (n = 29); 3) sporadic FTD (n = 72);
and 4) familial and sporadic FTD with MND (n = 40). Our studies confirm that the spectrum
of TDP-43 proteinopathies includes most cases of sporadic and familial FTLD-U with and
without MND and expand this disease spectrum to include reported families with FTD
linked to chromosome 9p but not FTD with charged multivesicular body protein 2B
mutations. Thus, despite significant clinical, genetic, and neuropathological heterogeneity
of FTLD-U, TDP-43 is a common pathological substrate underlying a large subset of these
disorders, thereby implicating TDP-43 in novel and unifying mechanisms of FTLD
pathogenesis
903. Cairns NJ, Bigio EH, Mackenzie IR et al. Neuropathologic diagnostic and nosologic criteria
for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal
Lobar Degeneration. Acta Neuropathol 2007;114(1):5-22.
Ref ID: 5815
Abstract: The aim of this study was to improve the neuropathologic recognition and provide
criteria for the pathological diagnosis in the neurodegenerative diseases grouped as
frontotemporal lobar degeneration (FTLD); revised criteria are proposed. Recent advances
in molecular genetics, biochemistry, and neuropathology of FTLD prompted the Midwest
Consortium for Frontotemporal Lobar Degeneration and experts at other centers to review
and revise the existing neuropathologic diagnostic criteria for FTLD. The proposed criteria
for FTLD are based on existing criteria, which include the tauopathies [FTLD with Pick
bodies, corticobasal degeneration, progressive supranuclear palsy, sporadic multiple
system tauopathy with dementia, argyrophilic grain disease, neurofibrillary tangle dementia,
and FTD with microtubule-associated tau (MAPT) gene mutation, also called FTD with
parkinsonism linked to chromosome 17 (FTDP-17)]. The proposed criteria take into account
new disease entities and include the novel molecular pathology, TDP-43 proteinopathy,
now recognized to be the most frequent histological finding in FTLD. TDP-43 is a major
component of the pathologic inclusions of most sporadic and familial cases of FTLD with
ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease
(MND). Molecular genetic studies of familial cases of FTLD-U have shown that mutations in
the progranulin (PGRN) gene are a major genetic cause of FTLD-U. Mutations in
valosin-containing protein (VCP) gene are present in rare familial forms of FTD, and some
families with FTD and/or MND have been linked to chromosome 9p, and both are types of
FTLD-U. Thus, familial TDP-43 proteinopathy is associated with defects in multiple genes,
and molecular genetics is required in these cases to correctly identify the causative gene
defect. In addition to genetic heterogeneity amongst the TDP-43 proteinopathies, there is
also neuropathologic heterogeneity and there is a close relationship between genotype and
FTLD-U subtype. In addition to these recent significant advances in the neuropathology of
FTLD-U, novel FTLD entities have been further characterized, including neuronal
intermediate filament inclusion disease. The proposed criteria incorporate up-to-date
neuropathology of FTLD in the light of recent immunohistochemical, biochemical, and
genetic advances. These criteria will be of value to the practicing neuropathologist and
provide a foundation for clinical, clinico-pathologic, mechanistic studies and in vivo models
of pathogenesis of FTLD
904. Caldas A, Boyer M, Dechaux M, Kleinknecht C. Primary distal tubular acidosis in childhood:
clinical study and long-term follow-up of 28 patients. J Pediatr 1992;121(2):233-241.
Ref ID: 1915
905. Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ. Maternal care
during infancy regulates the development of neural systems mediating the expression of
229
fearfulness in the rat. Proc Natl Acad Sci U S A 1998;95(9):5335-5340.
Ref ID: 2178
Abstract: The mothers of infant rats show individual differences in the frequency of
licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the
development of individual differences in behavioral responses to stress. As adults, the
offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced
behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN
mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i)
increased central benzodiazepine receptor density in the central, lateral, and basolateral
nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2
adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing
hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety
is regulated by a neural circuitry that includes the activation of ascending noradrenergic
projections from the locus ceruleus to the forebrain structures. Considering the importance
of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to
the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression
of behavioral responses to stress, these findings suggest that maternal care during infancy
serves to "program" behavioral responses to stress in the offspring by altering the
development of the neural systems that mediate fearfulness
906. Calhoun M, Longworth M, Chester VL. Gait patterns in children with autism. Clin Biomech
(Bristol , Avon ) 2010.
Ref ID: 6738
Abstract: BACKGROUND: Very few studies have examined the gait patterns of children
with autism. A greater awareness of movement deviations could be beneficial for treatment
planning. The purpose of this study was to compare kinematic and kinetic gait patterns in
children with autism versus age-matched controls. METHODS: Twelve children with autism
and twenty-two age-matched controls participated in the study. An eight camera motion
capture system and four force plates were used to compute joint angles and joint kinetics
during walking. Parametric analyses and principal component analyses were applied to
kinematic and kinetic waveform variables from the autism (n=12) and control (n=22)
groups. Group differences in parameterization values and principal component scores were
tested using one-way ANOVAs and Kruskal-Wallis tests. FINDINGS: Significant differences
between the autism and control group were found for cadence, and peak hip and ankle
kinematics and kinetics. Significant differences were found for three of the principal
component scores: sagittal ankle moment principal component one, sagittal ankle angle
principal component one, and sagittal hip moment principal component two. Results
suggest that children with autism demonstrate reduced plantarflexor moments and
increased dorsiflexion angles, which may be associated with hypotonia. Decreased hip
extensor moments were found for the autism group compared to the control group,
however, the clinical significance of this result is unclear. INTERPRETATION: This study
has identified several gait variables that were significantly different between autism and
control group walkers. This is the first study to provide a comprehensive analysis of gait
patterns in children with autism
907. Callaway E. Dyscalculia: Number games. Nature 2013;493(7431):150-153.
Ref ID: 7449
908. Campbell C, Cucci RA, Prasad S et al. Pendred syndrome, DFNB4, and PDS/SLC26A4
identification of eight novel mutations and possible genotype-phenotype correlations. Hum
Mutat 2001;17(5):403-411.
Ref ID: 4146
Abstract: Mutations in PDS (SLC26A4) cause both Pendred syndrome and DFNB4, two
autosomal recessive disorders that share hearing loss as a common feature. The hearing
loss is associated with temporal bone abnormalities, ranging from isolated enlargement of
the vestibular aqueduct (dilated vestibular aqueduct, DVA) to Mondini dysplasia, a complex
230
malformation in which the normal cochlear spiral of 2(1/2) turns is replaced by a hypoplastic
coil of 1(1/2) turns. In Pendred syndrome, thyromegaly also develops, although affected
persons usually remain euthyroid. We identified PDS mutations in the proband of 14 of 47
simplex families (30%) and nine of 11 multiplex families (82%) (P=0.0023). In all cases,
mutations segregated with the disease state in multiplex families. Included in the 15
different PDS allele variants we found were eight novel mutations. The two most common
mutations, T416P and IVS8+1G>A, were present in 22% and 30% of families, respectively.
The finding of PDS mutations in five of six multiplex families with DVA (83%) and four of
five multiplex families with Mondini dysplasia (80%) implies that mutations in this gene are
the major genetic cause of these temporal anomalies. Comparative analysis of phenotypic
and genotypic data supports the hypothesis that the type of temporal bone anomaly may
depend on the specific PDS allele variant present
909. Campbell DB, D'Oronzio R, Garbett K et al. Disruption of cerebral cortex MET signaling in
autism spectrum disorder. Ann Neurol 2007;62(3):243-250.
Ref ID: 5393
Abstract: OBJECTIVE: Multiple genes contribute to autism spectrum disorder (ASD)
susceptibility. One particularly promising candidate is the MET gene, which encodes a
receptor tyrosine kinase that mediates hepatocyte growth factor (HGF) signaling in brain
circuit formation, immune function, and gastrointestinal repair. The MET promoter variant
rs1858830 allele "C" is strongly associated with ASD and results in reduced gene
transcription. Here we examined expression levels of MET and members of the MET
signaling pathway in postmortem cerebral cortex from ASD cases and healthy control
subjects. METHODS: Protein, total RNA, and DNA were extracted from postmortem
temporal cortex gray matter samples (BA 41/42, 52, or 22) belonging to eight pairs of ASD
cases and matched control subjects. MET protein expression was determined by Western
blotting; messenger RNA expression of MET and other related transcripts was assayed by
microarray and quantitative reverse transcriptase polymerase chain reaction. RESULTS:
MET protein levels were significantly decreased in ASD cases compared with control
subjects. This was accompanied in ASD brains by increased messenger RNA expression
for proteins involved in regulating MET signaling activity. Analyses of coexpression of MET
and HGF demonstrated a positive correlation in control subjects that was disrupted in ASD
cases. INTERPRETATION: Altered expression of MET and related molecules suggests
dysregulation of signaling that may contribute to altered circuit formation and function in
ASD. The complement of genes that encode proteins involved in MET activation appears to
undergo long-term compensatory changes in expression that may be a hallmark
contribution to the pathophysiology of ASD
910. Campbell DB, Sutcliffe JS, Ebert PJ et al. A genetic variant that disrupts MET transcription
is associated with autism. Proc Natl Acad Sci U S A 2006;103(45):16834-16839.
Ref ID: 4966
Abstract: There is strong evidence for a genetic predisposition to autism and an intense
interest in discovering heritable risk factors that disrupt gene function. Based on
neurobiological findings and location within a chromosome 7q31 autism candidate gene
region, we analyzed the gene encoding the pleiotropic MET receptor tyrosine kinase in a
family based study of autism including 1,231 cases. MET signaling participates in
neocortical and cerebellar growth and maturation, immune function, and gastrointestinal
repair, consistent with reported medical complications in some children with autism. Here,
we show genetic association (P = 0.0005) of a common C allele in the promoter region of
the MET gene in 204 autism families. The allelic association at this MET variant was
confirmed in a replication sample of 539 autism families (P = 0.001) and in the combined
sample (P = 0.000005). Multiplex families, in which more than one child has autism,
exhibited the strongest allelic association (P = 0.000007). In case-control analyses, the
autism diagnosis relative risk was 2.27 (95% confidence interval: 1.41-3.65; P = 0.0006) for
the CC genotype and 1.67 (95% confidence interval: 1.11-2.49; P = 0.012) for the CG
genotype compared with the GG genotype. Functional assays showed that the C allele
231
results in a 2-fold decrease in MET promoter activity and altered binding of specific
transcription factor complexes. These data implicate reduced MET gene expression in
autism susceptibility, providing evidence of a previously undescribed pathophysiological
basis for this behaviorally and medically complex disorder
911. Campbell M, Armenteros JL, Malone RP, Adams PB, Eisenberg ZW, Overall JE.
Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am
Acad Child Adolesc Psychiatry 1997;36(6):835-843.
Ref ID: 3991
Abstract: OBJECTIVE: To report results from a long-term prospective study of safety of
haloperidol treatment and prevalence of haloperidol-related dyskinesias. METHOD:
Subjects were children with autism requiring pharmacotherapy for target symptoms. After
baseline assessments, children received haloperidol treatment; responders requiring
further treatment were considered for enrollment into the present study. Six-month
haloperidol treatment periods were followed by a 4-week placebo period. The procedure
was repeated if further haloperidol treatment was required. At specified times children were
evaluated by using multiple instruments. RESULTS: Between 1979 and 1994, 118 children
aged 2.3 to 8.2 years participated in the study. The mean dose of haloperidol was 1.75
mg/day. Mainly withdrawal dyskinesias (WD) developed in 40 (33.9%) children; 20 had
more than one dyskinetic episode. A subgroup that remained significantly longer in the
study and had a significantly higher cumulative dose of haloperidol evidenced a
significantly higher incidence of WD. Occurrence rates of tardive dyskinesia (TD) and
multiple episodes of TD/WD were higher among girls. CONCLUSION: Female gender and
pre- and perinatal complications may be involved in susceptibility to dyskinesias; greater
cumulative haloperidol dose and/or longer exposure to haloperidol may increase the risk
912. Campbell M, Anderson LT, Small AM, Adams P, Gonzalez NM, Ernst M. Naltrexone in
autistic children: Behavioral symptoms and attentional learning. J Am Acad Child Adolesc
Psychiatry 1993;32(6):1283-1291.
Ref ID: 1677
913. Campbell M, Small AM, Anderson LT, Malone RP, Locascio JJ. Pharmacotherapy in
autism. In: Naruse H, Ornitz EM, editors. Neurobiology of Infantile Autism. Amsterdam NL:
Excerpta Medica; 1992:235-243.
Ref ID: 99
914. Campbell M, Locascio JJ, Choroco MC et al. Stereotypies and tardive dyskinesia: abnormal
movements in autistic children. Psychopharmacol Bull 1990;26(2):260-266.
Ref ID: 3989
Abstract: Baseline stereotypic movements in 224 autistic children were studied as well as
their relationship to certain demographic variables and measures of overall
symptomatology and severity of illness. Prediction of haloperidol-related dyskinesias with
measures of stereotypies and demographic variables was also attempted. Stereotypies
were present in at least mild form in most children, with most showing moderate severity.
Most stereotypies were in the orofacial area. I.Q. was found to be negatively related to
stereotypies. Furthermore, across methods of assessment, severity and frequency of
stereotypies were found to be positively related to overall symptomatology and severity of
illness. No significant predictors of development of dyskinesias were found
915. Campbell M, Adams P, Perry R, Spencer EK, Overall JE. Tardive and withdrawal
dyskinesia in autistic children: a prospective study. Psychopharmacol Bull
1988;24(2):251-255.
Ref ID: 3990
232
916. Campbell M, Anderson LT, Meier M et al. A comparison of haloperidol, behavior therapy
and their interaction in autistic children. J Am Acad Child Psychiatry 1978;17:640-655.
Ref ID: 3704
917. Campbell TF, McNeil MR. Effects of presentation rate and divided attention on auditory
comprehension in children with an acquired language disorder. Journal of Speech &
Hearing Research 1985;28(4):513-520.
Ref ID: 2980
Abstract: We examined why auditory comprehension in language-disordered children
improves when the rate of presentation of speech is slowed. Seven children with an
acquired language disorder associated with a convulsive disorder participated in two
divided-attention tasks in which pairs of sentences were presented simultaneously.
Subjects were instructed to respond first to the sentence produced by a male speaker
(primary sentence) and then to the sentence produced by a female speaker (secondary
sentence). In the first condition, both sentences were presented at a normal rate of speech.
In the second condition, primary sentences were time expanded 75%, and secondary
sentences were presented at a normal rate. We hypothesized that when the primary
sentences were presented slowly, spare attention would be available for processing the
secondary sentences. Results showed that slowing the presentation rate of the primary
sentences significantly improved performance on the secondary sentences, even though
secondary sentences were presented at a normal rate of speech. Hypotheses of generally
slowed processing of auditory information in language-disordered individuals cannot
account for these results. They are consistent, however, with a model of defective attention
allocation
918. Campion EW. Suspicions about the safety of vaccines. N Engl J Med
2002;347(19):1474-1475.
Ref ID: 3675
919. Canales JJ, Graybiel AM. A measure of striatal function predicts motor stereotypy. Nat
Neurosci 2000;3(4):377-383.
Ref ID: 3949
Abstract: To identify basal ganglia circuit dysfunctions that might produce repetitive
behaviors known as motor stereotypies, we applied psychomotor stimulants and a direct
dopamine receptor agonist to induce different levels of stereotypy in rats. We then used a
gene induction assay to measure the functional activation of neurons in the
neurochemically distinct compartments of the striatum, the striosomes and the
extrastriosomal matrix. The amount by which activation in the striosomes exceeded
activation in the matrix predicted the degree of motor stereotypy induced by the drug
treatments. These results suggest that imbalance between compartmentally organized
basal ganglia circuits may represent a neural correlate of motor stereotypy
920. Canitano R, Vivanti G. Tics and Tourette syndrome in autism spectrum disorders. Autism
2007;11(1):19-28.
Ref ID: 5279
Abstract: Autism spectrum disorders (ASDs) are more frequently associated with tic
disorders than expected by chance. Variable rates of comorbidity have been reported and
common genetic and neurobiological factors are probably involved. The aim of this study
was to determine the rate of tic disorders in a clinical sample (n = 105) of children and
adolescents with ASDs and to describe the clinical characteristics of a group with comorbid
ASDs and tics (n = 24). The overlap between tics and other repetitive movements and
behaviors in ASDs was carefully assessed. Among individuals with ASDs, 22 percent
presented tic disorders: 11 percent with Tourette disorder (TD), and 11 percent with chronic
motor tics. All had various degrees of cognitive impairment. An association between the
level of mental retardation and tic severity was found. It is concluded that the occurrence of
tics in ASDs should not be overlooked and should be carefully evaluated
233
921. Canitano R, Luchetti A, Zappella M. Epilepsy, electroencephalographic abnormalities, and
regression in children with autism. J Child Neurol 2005;20(1):27-31.
Ref ID: 5280
Abstract: The association of epilepsy and autism is recognized, and it has been reported at
a percentage that varies between 8 and 42%, depending on age and diagnostic criteria.
One third of autistic children undergo a regression of language and behavior between 2
and 3 years, and epileptiform abnormalities and epilepsy can be concomitant in an
undetermined percentage of them. The aim of this study was to investigate the prevalence
of epilepsy and paroxysmal abnormalities in a group of children with autism and to
determine the percentage of regression course in this group. Forty-six patients with autism
(mean age 7.8 +/- 2.7 years; 34 boys and 12 girls) were consecutively examined, and
clinical evaluation, assessment, and electroencephalographic (EEG) recordings were
performed in all of them. Thirty-five percent showed paroxysmal abnormalities and
epilepsy, 22% had only paroxysmal abnormalities without seizures, and 13% of the children
suffered from epilepsy. Sixty-five percent had a normal EEG. No difference in regression
rate was observed between patients with paroxysmal abnormalities and epilepsy and those
with a normal EEG and without seizures. In the study group, the prevalence of epilepsy
was in the low range of individuals with autism, and different types of epilepsy were
observed. Autism with regression was not influenced by paroxysmal abnormalities and
epilepsy
922. Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: historical
and meta-analytic review. Am J Psychiatry 2002;159(7):1080-1092.
Ref ID: 7199
Abstract: OBJECTIVE: This paper reviews the literature on obstetric complications as a risk
factor for schizophrenia. The authors trace the evolution of this literature through different
methods and carry out a quantitative review of the results from prospective,
population-based studies. METHOD: Relevant papers were identified by a MEDLINE
search, by examination of reference lists of published papers, and through personal contact
with researchers in the field. Studies were grouped in chronological order according to
common themes or methods. Meta-analytic techniques were used to summarize the
findings of prospective population-based studies. RESULTS: The meta-analytic synthesis
of the prospective population-based studies revealed that three groups of complications
were significantly associated with schizophrenia: 1) complications of pregnancy (bleeding,
diabetes, rhesus incompatibility, preeclampsia); 2) abnormal fetal growth and development:
(low birthweight, congenital malformations, reduced head circumference), and 3)
complications of delivery (uterine atony, asphyxia, emergency Cesarean section). Pooled
estimates of effect sizes were generally less than 2. CONCLUSIONS: Current methods of
investigating the relationship between obstetric complications and schizophrenia are
reaching the limit of their usefulness. Lack of statistical power to measure small and
interactive effects and lack of detailed information about the prenatal period are major
problems with current approaches. A combination of disciplines and approaches will be
needed to elucidate the mechanisms underlying these small but important associations
923. Cannon M, Caspi A, Moffitt TE et al. Evidence for early-childhood, pan-developmental
impairment specific to schizophreniform disorder: results from a longitudinal birth cohort.
Arch Gen Psychiatry 2002;59(5):449-456.
Ref ID: 7200
Abstract: BACKGROUND: Childhood developmental abnormalities have been previously
described in schizophrenia. It is not known, however, whether childhood developmental
impairment is specific to schizophrenia or is merely a marker for a range of psychiatric
outcomes. METHODS: A 1-year birth cohort (1972-1973) of 1037 children enrolled in the
Dunedin Multidisciplinary Health and Development Study was assessed at biennial
intervals between ages 3 and 11 years on emotional, behavioral, and interpersonal
problems, motor and language development, and intelligence. At age 11 years, children
were asked about psychotic symptoms. At age 26 years, DSM-IV diagnoses were made
234
using the Diagnostic Interview Schedule. Study members having schizophreniform disorder
(n = 36 [3.7%]) were compared with healthy controls and also with groups diagnosed as
having mania (n = 20 [2%]) and nonpsychotic anxiety or depression disorders (n = 278
[28.5%]) on childhood variables. RESULTS: Emotional problems and interpersonal
difficulties were noted in children who later fulfilled diagnostic criteria for any of the adult
psychiatric outcomes assessed. However, significant impairments in neuromotor, receptive
language, and cognitive development were additionally present only among children later
diagnosed as having schizophreniform disorder. Developmental impairments also predicted
self-reported psychotic symptoms at age 11 years. These impairments were independent of
the effects of socioeconomic, obstetric, and maternal factors. CONCLUSIONS: The results
provide evidence for an early-childhood, persistent, pan-developmental impairment that is
specifically associated with schizophreniform disorder and that predicts psychotic
symptoms in childhood and adulthood
924. Cantlon JF, Pinel P, Dehaene S, Pelphrey KA. Cortical representations of symbols, objects,
and faces are pruned back during early childhood. Cereb Cortex 2011;21(1):191-199.
Ref ID: 7551
Abstract: Regions of human ventral extrastriate visual cortex develop specializations for
natural categories (e.g., faces) and cultural artifacts (e.g., words). In adults, category-based
specializations manifest as greater neural responses in visual regions of the brain (e.g.,
fusiform gyrus) to some categories over others. However, few studies have examined how
these specializations originate in the brains of children. Moreover, it is as yet unknown
whether the development of visual specializations hinges on "increases" in the response to
the preferred categories, "decreases" in the responses to nonpreferred categories, or
"both." This question is relevant to a long-standing debate concerning whether neural
development is driven by building up or pruning back representations. To explore these
questions, we measured patterns of visual activity in 4-year-old children for 4 categories
(faces, letters, numbers, and shoes) using functional magnetic resonance imaging. We
report 2 key findings regarding the development of visual categories in the brain: 1) the
categories "faces" and "symbols" doubly dissociate in the fusiform gyrus before children
can read and 2) the development of category-specific responses in young children depends
on cortical responses to nonpreferred categories that decrease as preferred category
knowledge is acquired
925. Cantlon JF, Safford KE, Brannon EM. Spontaneous analog number representations in
3-year-old children. Dev Sci 2010;13(2):289-297.
Ref ID: 7466
Abstract: When enumerating small sets of elements nonverbally, human infants often show
a set-size limitation whereby they are unable to represent sets larger than three elements.
This finding has been interpreted as evidence that infants spontaneously represent small
numbers with an object-file system instead of an analog magnitude system (Feigenson,
Dehaene & Spelke, 2004). In contrast, non-human animals and adult humans have been
shown to rely on analog magnitudes for representing both small and large numbers
(Brannon & Terrace, 1998; Cantlon & Brannon, 2007; Cordes, Gelman, Gallistel & Whalen,
2001). Here we demonstrate that, like adults and non-human animals, children as young as
3 years of age spontaneously employ analog magnitude representations to enumerate both
small and large sets. Moreover, we show that children spontaneously attend to numerical
value in lieu of cumulative surface area. These findings provide evidence of young
children's greater sensitivity to number relative to other quantities and demonstrate
continuity in the process they spontaneously recruit to judge small and large values
926. Cantlon JF, Libertus ME, Pinel P, Dehaene S, Brannon EM, Pelphrey KA. The neural
development of an abstract concept of number. J Cogn Neurosci 2009;21(11):2217-2229.
Ref ID: 7467
Abstract: As literate adults, we appreciate numerical values as abstract entities that can be
represented by a numeral, a word, a number of lines on a scorecard, or a sequence of
235
chimes from a clock. This abstract, notation-independent appreciation of numbers develops
gradually over the first several years of life. Here, using functional magnetic resonance
imaging, we examine the brain mechanisms that 6- and 7-year-old children and adults
recruit to solve numerical comparisons across different notation systems. The data reveal
that when young children compare numerical values in symbolic and nonsymbolic
notations, they invoke the same network of brain regions as adults including
occipito-temporal and parietal cortex. However, children also recruit inferior frontal cortex
during these numerical tasks to a much greater degree than adults. Our data lend
additional support to an emerging consensus from adult neuroimaging, nonhuman primate
neurophysiology, and computational modeling studies that a core neural system integrates
notation-independent numerical representations throughout development but, early in
development, higher-order brain mechanisms mediate this process
927. Cantor RM, Kono N, Duvall JA et al. Replication of autism linkage: fine-mapping peak at
17q21. Am J Hum Genet 2005;76(6):1050-1056.
Ref ID: 4522
Abstract: Autism is a heritable but genetically complex disorder characterized by deficits in
language and in reciprocal social interactions, combined with repetitive and stereotypic
behaviors. As with many genetically complex disorders, numerous genome scans reveal
inconsistent results. A genome scan of 345 families from the Autism Genetic Resource
Exchange (AGRE) (AGRE_1), gave the strongest evidence of linkage at 17q11-17q21 in
families with no affected females. Here, we report a full-genome scan of an independent
sample of 91 AGRE families with 109 affected sibling pairs (AGRE_2) that also shows the
strongest evidence of linkage to 17q11-17q21 in families with no affected females. Taken
together, these samples provide a replication of linkage to this chromosome region that is,
to our knowledge, the first such replication in autism. Fine mapping at 2-centimorgan (cM)
intervals in the combined sample of families with no affected females reveals a linkage
peak at 66.85 cM, which places this locus at 17q21
928. Cantos R, Lopez DE, Merchan JA, Rueda J. Olivocochlear efferent innervation of the organ
of corti in hypothyroid rats. J Comp Neurol 2003;459(4):454-467.
Ref ID: 6258
Abstract: Congenital hypothyroidism induces developmental abnormalities in the auditory
receptor, causing deafness due to a poor development of the outer hair cells (OHCs) and a
lack of synaptogenesis between these cells and the olivocochlear axons. This efferent
innervation is formed by two separate systems: the lateral system, which originates in the
lateral superior olive (LSO) and reaches the inner hair cells; and the medial system, which
originates in the ventral nucleus of the trapezoid body (VNTB) and innervates the OHCs. A
previous study carried out in our laboratory showed that in congenitally hypothyroid
animals, the neurons which give rise to the efferent system are normal in number and
distribution, although smaller in size. The aim of the present work was to study the efferent
fibers in the auditory receptor of hypothyroid animals, by means of stereotaxic injections of
biotinylated dextran amine in the nuclei that give rise to the olivocochlear system: LSO and
VNTB. In hypothyroid animals, injections in LSO gave rise to lateral olivocochlear fibers
lacking their characteristic dense terminal arbors, while injections in the VNTB-labeled
fibers terminating in the spiral bundle region, far from the OHCs with which they normally
contact. In the latter case, only a small percentage of labeled fibers reached the OHCs
area, giving off only two radial branches maximum. Because the number of neurons which
develop into the efferent innervation was normal in hypothyroid animals, we conclude that
medial fibers may contact a new target
929. Cantwell DP, Baker L, Rutter M, Manwood L. Infantile autism and developmental receptive
dysphasia: A comparative follow-up into middle childhood. J Autism Dev Disord
1989;19:19-31.
Ref ID: 915
236
930. Cantwell DP, Baker L. Clinical significance of childhood communication disorders:
Perspectives from a longitudinal study. J Child Neurol 1987;2:257-264.
Ref ID: 2998
Abstract: A group of 202 children who were referred for evaluation of communication
disorders were also evaluated for psychiatric and learning disorders at two points in time.
High rates of both psychiatric and learning disorders were found at initial evaluation, and
even higher rates were found at follow-up 3 to 4 years later. Recovery from communication
disorder occurred in approximately one fourth of the cases and varied widely depending on
the type of disorder involved. Poor psychiatric outcome could be predicted by the presence
and severity of initial disorders of language comprehension and expression, and by certain
environmental factors (such as psychosocial stress). The high prevalence of linguistic,
psychiatric, and development disorders at follow-up for the children in this study suggests
the need for close monitoring of children with early communication impairments.
931. Cantwell DP, Baker L, Rutter M. Families of autistic and dysphasic children. I. Family life
and interaction patterns. Arch Gen Psychiat 1979;36:682-687.
Ref ID: 187
932. Cantwell DP, Baker L, Rutter M. A comparative study of infantile autism and specific
development receptive language disorder: IV. Analysis of syntax and language function. J
Child Psychol Psychiatry 1978;19:351-362.
Ref ID: 916
933. Caplan R. Epilepsy in early development: The lesson from surgery for early intractable
seizures. Sem Pediat Neurol 1995;4:240-245.
Ref ID: 430
934. Capovilla G, Lorenzetti ME, Montagnini A et al. Seckel's syndrome and malformations of
cortical development: report of three new cases and review of the literature. J Child Neurol
2001;16(5):382-386.
Ref ID: 4573
Abstract: Seckel's syndrome is a rare form of primordial dwarfism, characterized by peculiar
facial appearance. In the past, this condition was overdiagnosed, and most attention was
given to the facial and skeletal features to define more precise diagnostic criteria. The
presence of mental retardation and neurologic signs is one of the peculiar features of this
syndrome, but only recently were rare cases of malformation of cortical development
described, as documented by magnetic resonance imaging (MRI). Here, we present three
new cases of Seckel's syndrome showing different malformations of cortical development
(one gyral hypoplasia, one macrogyria and partial corpus callosum agenesis, and one
bilateral opercular macrogyria). We hypothesize that the different types of clinical
expression of our patients could be explained by different malformation of cortical
development types. We think that MRI studies could be performed in malformative
syndromes because of the possible correlations between type and extent of the lesion and
the clinical picture of any individual case
935. Cappelletti M, Barth H, Fregni F, Spelke ES, Pascual-Leone A. rTMS over the intraparietal
sulcus disrupts numerosity processing. Exp Brain Res 2007;179(4):631-642.
Ref ID: 7535
Abstract: It has been widely argued that the intraparietal sulcus (IPS) is involved in tasks
that evoke representations of numerical magnitude, among other cognitive functions.
However, the causal role of this parietal region in processing symbolic and non-symbolic
numerosity has not been established. The current study used repetitive Transcranial
Magnetic Stimulation (rTMS) to the left and right IPS to investigate the effects of temporary
deactivations of these regions on the capacity to represent symbolic (Arabic numbers) and
non-symbolic (arrays of dots) numerosities. We found that comparisons of both symbolic
and non-symbolic numerosities were impaired after rTMS to the left IPS but enhanced by
237
rTMS to the right IPS. A signature effect of numerical distance was also found: greater
impairment (or lesser facilitation) when comparing numerosities of similar magnitude. The
reverse pattern of impairment and enhancement was found in a control task that required
judging an analogue stimulus property (ellipse orientation) but no numerosity judgements.
No rTMS effects for the numerosity tasks were found when stimulating an area adjacent but
distinct from the IPS, the left and right angular gyrus. These data suggest that left IPS is
critical for processing symbolic and non-symbolic numerosity; this processing may thus
depend on common neural mechanisms, which are distinct from mechanisms supporting
the processing of analogue stimulus properties
936. Cappon D. Clinical manifestations of autism and schizophrenia in childhood. Can Med
Assoc J 1953;69(1):44-49.
Ref ID: 7050
937. Capute AJ, Palmer FB, Shapiro BK. Clinical Linguistic and Auditory Milestone Scale:
prediction of cognition in infancy. Dev Med Child Neurol 1986;28:762-771.
Ref ID: 2985
938. Capute AJ, Accardo PJ. Linguistic and auditory milestones in the first two years of life: A
language inventory for the practicing pediarician. Clin Pediatr 1978;17:847-853.
Ref ID: 458
939. Caramazza A. Language: Introduction. In: Gazzaniga MS, editor. The cognitive
neurosciences III. 3 ed. Cambridge MA: MIT Press; 2004:755-757.
Ref ID: 5352
940. Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC.
Quantitative trait locus for reading disability on chromosome 6. Science 1994;266:276-279.
Ref ID: 1173
941. Carelli V, La MC, Valentino ML, Barboni P, Ross-Cisneros FN, Sadun AA. Retinal ganglion
cell neurodegeneration in mitochondrial inherited disorders. Biochim Biophys Acta
2009;1787(5):518-528.
Ref ID: 6350
Abstract: Since the early days of mitochondrial medicine, it has been clear that optic
atrophy is a very common and sometimes the singular pathological feature in mitochondrial
disorders. The first point mutation of mitochondrial DNA (mtDNA) associated with the
maternally inherited blinding disorder, Leber's hereditary optic neuropathy (LHON), was
recognized in 1988. In 2000, the other blinding disorder, dominant optic atrophy (DOA) Kjer
type, was found associated with mutations in the nuclear gene OPA1 that encodes a
mitochondrial protein. Besides these two non-syndromic optic neuropathies, optic atrophy
is a prominent feature in many other neurodegenerative diseases that are now recognized
as due to primary mitochondrial dysfunction. We will consider mtDNA based syndromes
such as LHON/dystonia/Mitochondrial Encephalomyopahty Lactic Acidosis Stroke-like
(MELAS)/Leigh overlapping syndrome, or nuclear based diseases such as Friedreich
ataxia (mutations in FXN gene), deafness-dystonia-optic atrophy (Mohr-Tranebjerg)
syndrome (mutations in TIMM8A), complicated hereditary spastic paraplegia (mutations in
SPG7), DOA "plus" syndromes (mutations in OPA1), Charcot-Marie-Tooth type 2A
(CMT2A) with optic atrophy or hereditary motor and sensory neuropathy type VI (HMSN VI)
(mutations in MFN2), and Costeff syndrome and DOA with cataract (mutations in OPA3).
Thus, genetic errors in both nuclear and mitochondrial genomes often lead to retinal
ganglion cell death, a specific target for mitochondrial mediated neurodegeneration. Many
mechanisms have been studied and proposed as the bases for the pathogenesis of
mitochondrial optic neuropathies including bioenergetic failure, oxidative stress, glutamate
toxicity, abnormal mitochondrial dynamics and axonal transport, and susceptibility to
apoptosis
238
942. Carey G, Gottesman II. Reliability and validity in binary ratings. Arch Gen Psychiat
1978;35:1454-1459.
Ref ID: 1208
943. Carlsson G, Uvebrant P, Hugdahl K, Arvidsson J, Wiklund LM, von WL. Verbal and
non-verbal function of children with right- versus left-hemiplegic cerebral palsy of pre- and
perinatal origin. Dev Med Child Neurol 1994;36(6):503-512.
Ref ID: 6386
Abstract: Eighteen children with right- and 13 with left-sided congenital hemiplegia were
compared with 19 normal age-matched controls for verbal and non-verbal function. CT
scans were obtained from 27 of the 31 hemiplegic children. The two hemiplegic groups
were impaired in non-verbal function compared with controls. The right-hemiplegic group
was more impaired in verbal function than the left-hemiplegic group and controls; however,
impairments were restricted to the girls in the right-hemiplegic group. The results are
discussed in terms of cerebral plasticity and functional reorganisation of cognitive functions
after an early unilateral injury. It is argued that girls with left-hemisphere lesions may be
more limited in cerebral plasticity than boys
944. Carlsson G, Hugdahl K, Uvebrant P, Wiklund LM, von WL. Pathological left-handedness
revisited: dichotic listening in children with left vs right congenital hemiplegia.
Neuropsychologia 1992;30(5):471-481.
Ref ID: 6387
Abstract: Thirty-one children with right (n = 18) and left (n = 13) congenital hemiplegia were
compared for incidence of hand- and foot-preference, eye-dominance, and familial
sinistrality. In addition, they were tested with dichotic listening for correct reports of
consonant-vowel syllables. The two groups of children were closely matched on IQ and
sensory functioning. Children with mental retardation, or epileptic seizures were not
included. The results showed that 89% of the left hemisphere impaired (LHI) children were
left-handed, all of them preferred the left foot, and 72% were left eye-dominant. In the right
hemisphere impaired (RHI) group, everyone (100%) preferred the right hand and foot, and
62% were right eye dominant. The dichotic listening results showed a significant right ear
advantage (REA) in the RHI-group, and a significant left ear advantage (LEA) in the
LHI-group. The results are discussed in the framework of pathological handedness and
shifts in hemisphere control of language in children with early brain injury. It is argued that
the homogeneous samples, except for the site of lesion, provides an interesting possibility
to compare cognitive effects of left and right hemisphere impairment in children
239