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Contents lists available at ScienceDirect
Journal of Communication Disorders
Auditory temporal processing deficits and language disorders
in patients with neurofibromatosis type 1
Pollyanna Barros Batista a, Stela Maris Aguiar Lemos b,
Luiz Oswaldo Carneiro Rodrigues c, Nilton Alves de Rezende d,*
a
Federal University of Minas Gerais, Brazil
Department of Speech Therapy and Audiology at the Federal University of Minas Gerais, Brazil
Clinical Coordinator at the Neurofibromatosis Outpatient Reference Center (NFRC), Dermatology Service, Clinics Hospital of the Federal
University of Minas Gerais, Brazil
d
Clinical Director of NFRC, Department of Internal Medicine, Federal University of Minas Gerais, Brazil
b
c
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 14 April 2013
Received in revised form 20 December 2013
Accepted 23 December 2013
Available online xxx
Previous findings from a case report led to the argument of whether other patients with
neurofibromatosis type 1 (NF1) may have abnormal central auditory function, particularly
auditory temporal processing. We hypothesized that it is associated with language and
learning disabilities in this population. The aim of this study was to measure central
auditory temporal function in NF1 patients and correlate it with the results of language
evaluation tests. A descriptive/comparative study including 25 NF1 individuals and 22
healthy controls compared their performances on audiometric evaluation and auditory
behavioral testing (Sequential Verbal Memory, Sequential Non-Verbal Memory, Frequency Pattern, Duration Pattern, and Gaps in Noise Tests). To assess language
performance, two tests (phonological and syntactic awareness) were also conducted.
The study showed that all participants had normal peripheral acoustic hearing. Differences
were found between the NF1 and control groups in the temporal auditory processing tests
[Sequential Verbal Memory (P = 0.009), Sequential Non-Verbal Memory (P = 0.028),
Frequency Patterns (P = 0.001), Duration Patterns (P = 0.000), and Gaps in Noise
(P = 0.000)] and in language tests. The results of Pearson correlation analysis demonstrated
the presence of positive correlations between the phonological awareness test and
Frequency Patterns humming (r = 0.560, P = 0.001), Frequency Patterns labeling (r = 0.415,
P = 0.022) and Duration Pattern humming (r = 0.569, P = 0.001). These results suggest that
the neurofibromin deficiency found in NF1 patients is associated with auditory temporal
processing deficits, which may contribute to the cognitive impairment, learning
disabilities, and attention deficits that are common in this disorder.
Learning outcomes: The reader will be able to: (1) describe the auditory temporal
processing in patients with neurofibromatosis type 1; and (2) describe the impact of the
auditory temporal deficits in language in this population.
ß 2014 Elsevier Inc. All rights reserved.
Keywords:
Neurofibromatosis type 1
Auditory temporal processing
Hearing disorders
Language
Learning disabilities
Cognitive deficits
Abbreviations: AP, auditory processing; ATPD, auditory temporal processing deficits; CNS, central nervous system; DP, Duration Patterns; FP,
Frequency Patterns; GIN, Gaps in Noise; HL, hearing level; NF1, neurofibromatosis type 1; NHI, National Institutes of Health; SNVM, Sequential NonVerbal Memory; SVM, Sequential Verbal Memory.
* Corresponding author at: Aimorés, 462/116, Funcionários, Belo Horizonte, MG, P.O. Box 30140-070, Brazil. Tel.: +55 3199789545; fax: +55 3132267738.
E-mail addresses: narezende@terra.com.br, nilton.a.rezende@gmail.com (N.A. de Rezende).
0021-9924/$ – see front matter ß 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jcomdis.2013.12.002
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
j.jcomdis.2013.12.002
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1. Introduction
Neurofibromatosis type 1 (NF1) is a genetic disease that affects 1:3000 people (Friedman, 1999; Lammert, Friedman,
Kluwe, & Mautner, 2005; Lee & Stephenson, 2007; Souza, Toledo, Ferreira, Rodrigues, & Rezende, 2009). The NF1 gene is
located on the long arm of chromosome 17 (17q11.2) (Feldkamp, Gutmann, & Guha, 1998; Ledbetter, Rich, O’Connell,
Leppert, & Carey, 1989), and mutations of this gene result in loss of the protein neurofibromin (Viskochil et al., 1990; Wallace
et al., 1990), which is a cellular growth suppressor that also affects synaptic plasticity, memory, and learning (Johnston, 2003,
2004). The diagnosis of NF1 requires the presence of 2 of the National Institutes of Health (NHI) criteria: café au lait spots,
cutaneous and/or plexiform neurofibromas, iris Lisch nodules, axillary and/or groin freckling, optic glioma, specific osseous
dysplasia, or an affected first-degree relative.
Communication disorder studies in NF1 patients have focused on voice impairments, oral/motor dysfunction,
language disorders, learning disabilities, and hearing disorders. It is reported that between 30% and 65% of children with
NF1 exhibit learning disabilities (Hyman, Shores, & North, 2005). Difficulties in reading, spelling, and expressive and
receptive language are also observed in NF1 patients (Coudé, Mignot, Lyonnet, & Munnich, 2006; Ferner, Hughes, &
Weinman, 1996; Lorch, Ferner, Golding, & Whurr, 1999). Although hearing loss is the main symptom in
neurofibromatosis type 2 patients, it is also an important complication in NF1 patients, because the latter are at risk
of developing hearing loss, deafness, or abnormal auditory brainstem responses (Pikus, 1995; Poissant, Megerian, &
Hume, 2003; Tonsgard, 2006).
Batista, Silva, Valentim, Rodrigues, and Rezende (2010) suspected that auditory system involvement affected language
and learning in an NF1 patient (male, 31 years old) with learning and language disorders. His auditory processing (AP) was
evaluated via different objective tests (pure-tone audiometric and immittance audiometry) and behavioral auditory tests:
Sound Localization, Speech in Noise, Dichotic Digits, Staggered Spondaic Word, Dichotic Non-Verbal, Sequential Verbal
Memory (SVM), Sequential Non-Verbal Memory (SNVM), Frequency Patterns (FP), and Duration Patterns (DP). An evaluation
of his reading and writing was conducted, as well as a phonological and syntactic awareness tests. The diagnosis of auditory
processing disorder (APD) was confirmed by his normal performance on peripheral evaluations and the presence of severe
abnormal auditory abilities: auditory closure, auditory figure ground, auditory selective attention, auditory memory, and
temporal processing. Alterations in the temporal processing were the main findings in this case report, and were correlated
with his poor phonological and syntactic abilities.
AP is the ability of the central nervous system (CNS) to use auditory inputs. More specifically, it ‘‘refers to the perceptual
processing of auditory information in the CNS and the neurobiological activity that underlies that processing and gives rise to
electrophysiological auditory potentials’’ (ASHA, 2005). This impaired ability results in APD, which manifests itself as
difficulties in listening in challenging listening environments, in localizing sound sources, and in processing rapid acoustic
stimuli. An APD can affect an individual’s listening, spoken language comprehension, and learning abilities (ASHA, 1996);
thus, it is important to diagnose and treat this disorder.
Auditory temporal processing (ATP) represents an important aspect of auditory processing functioning and can be
defined as the perception of the temporal characteristics of a sound or the alteration of durational characteristics
within a restricted or defined time interval (Musiek et al., 2005). Temporal processing is critical to a wide variety
of everyday listening tasks, including perception of speech and music (Hirsh, 1959). It comprises 4 subcomponents:
(1) temporal ordering or sequencing; (2) temporal resolution or discrimination; (3) temporal masking, and (4)
temporal integration (ASHA, 2005). Temporal ordering or sequencing refers to the perception and processing
of the order of two or more auditory stimuli over time (Pinheiro & Musiek, 1985). Temporal resolution or
discrimination is the ability to follow rapid changes in the envelope of an auditory stimulus over time (Viemeister &
Plack, 1993). Temporal integration refers to the ability of the auditory system to integrate information over time to
enhance the detection or discrimination of stimuli, and temporal masking refers to the psychoacoustical phenomenon of
shifting of the threshold of one sound because of the presence of another masking sound that precedes or follows it
(Moore, 2003).
Several authors have argued that a temporal processing deficit affects the sensory input that is needed for the proper
phonological coding that is critically required in writing (Tallal, 1980) and reading (Mody, 2003). Such a deficit may
hamper the learning of precise relations between word sounds and letter sounds, leading to difficulties in associating the
printed letter (grapheme) with the appropriate speech sound (phoneme). The theory proposed by Tallal (1980) suggests
that difficulties in resolving rapid temporal changes in sound at the level of phonemes of speech may result in poor
phonemic awareness and literacy acquisition. In severe cases, this could also lead to problems in the learning of
vocabulary and syntax.
Motivated by the findings of the previous study performed by Batista et al. (2010), we hypothesized that APD is associated
with language disorders in NF1 patients. The purpose of the present study was to assess central auditory temporal function
in a group of NF1 patients and healthy controls, and to correlate it with language performance.
2. Materials and methods
This study was approved by the Ethics Committee of the Federal University of Minas Gerais (#175/10), and informed
consent was obtained from all participants or their parents.
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
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2.1. Study population
All volunteers were patients with a clinical diagnosis based on NF1 criteria (National Institutes of Health Consensus
Development Conference Statement: neurofibromatosis, 1988). Patients were aged 10–35 years, included 11 males and 14
females, and were recruited from the Neurofibromatosis Outpatient Reference Center at the Clinics Hospital of the Federal
University of Minas Gerais, Belo Horizonte, Brazil. The control group consisted of age- and sex-matched healthy individuals
with no history of auditory or language deficits. All patients and controls were Portuguese speakers and had normal
peripheral hearing. Participants with segmental NF1, poor comprehension of the Portuguese language, or severe vision
impairment were excluded. All participants completed standard baseline audiometric tests, behavioral tests for central
auditory function, and language tests, which were all administered by the same investigator (PBB).
2.2. Peripheral auditory evaluation
Pure-tone audiometric measurement was carried out to ensure normal function of the peripheral auditory mechanism.
Normal peripheral hearing was defined as an air conduction threshold of 25 dB hearing level (HL) or better at octave
frequencies from 250 to 8000 Hz (ANSI S3.6). Participants were evaluated with a Beta 6000 clinical audiometer (Beta
Medical, São Paulo, BR) in a quiet room with an ambient noise level 30 dB, using the procedure recommended by ANSI S31991. A Homis model 910ß decibel meter (Homis Controle e Instrumentação Ltda., São Paulo, BR) was used to measure sound
intensity (dB SPL).
2.3. Auditory temporal processing evaluation
An auditory temporal processing evaluation was performed using the battery of 5 validated central auditory tests
summarized in Table 1. These tests were chosen on the basis of the abilities evaluated (i.e., primarily temporal ordering and
temporal resolution) and whether the test required a diotic or monotic task. Diotic refers to a situation in which identical
stimuli are presented simultaneously to both ears, and monotic is a condition in which a stimulus is presented to only one ear
(Bellis, 2003).
Sequential Verbal Memory testing was conducted with the syllables ‘‘pa’’, ‘‘ta’’, ‘‘ca’’, and ‘‘fa’’ (as pronounced in
Portuguese) sorted in 3 different sequences. First, to determine if participants were able to produce the syllables, the listener
was asked to speak and repeat each syllable independently. Three sequences of 4 syllables were then presented without
visual cues, and the participant was asked to reproduce them orally. A normal SVM score was defined as 2 correct responses
in 3 attempts (Corona, Pereira, Ferrita, & Rossi, 2005).
Sequential Non-Verbal Memory testing was conducted using the following instruments: bell, agogo (a Brazilian musical
instrument that consists of 2 metallic rectangular bells connected to a metallic base), rattle, and coconut. First, the sounds
produced by the 4 instruments were presented to the listener. The participant was then positioned in front of the
instruments and a sound demonstration was performed. The listener was asked to identify the correct order in which the
instruments were presented. Finally, the participant was blindfolded and 3 different sequences of the 4 instruments were
presented, and the participant was asked to identify the correct order of instruments. A normal SNVM score was defined as
2 correct responses in 3 attempts (Pereira, 1996).
The Frequency Patterns Test consisted of 30 patterned sequences that were presented diotically, each one consisting of 3
tone bursts in varying patterns of high (1122 Hz) and low (880 Hz) frequencies. Each sequence was composed of 2 bursts of
the same and 1 burst of a different frequency. In this test, 15 items are first presented and the participant is asked to hum the
pattern. Subsequently, 15 new items are presented and the participant is asked to verbally report the pattern (e.g., high/low/
high). The outcome measure is the percentage of correct responses. A normal FP score was defined as 69% for children aged
10–12 years and 76% for those aged 12 years and above (including adults) (Musiek, 1994). The individual results were
categorized as ‘‘normal’’ or ‘‘altered’’ and statistical analyses were performed.
The Duration Patterns Test is similar to the FP Test. However, the stimuli differ with respect to duration (either 250 or
500 ms) rather than frequency. Subjects were asked to hum or verbally describe the pattern heard (e.g., long/short/long). The
outcome measure is the percentage of correct responses. A normal DP score was defined as 64% for children aged 10–12
Table 1
Battery of tests used to assess auditory temporal processing.
Test
Stimulus
Task
Answer required
Auditory ability evaluated
Sequential Verbal Memory
Sequential Non-Verbal Memory
Frequency Patterns Test
Syllables
Musical sounds
Tones differing in
frequency
Tones differing in
duration
Gaps in noise
Diotic
Diotic
Diotic
Reproduce the sequence orally
Identify the musical instrument
Humming and labeling
Temporal ordering of verbal sounds
Temporal ordering of nonverbal sounds
Temporal ordering; Frequency discrimination
Diotic
Humming and labeling
Temporal ordering; Duration discrimination
Monotic
Motor
Temporal resolution
Duration Patterns Test
Gaps in Noise
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
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years and 83% for those aged 12 years and above (including adults) (Musiek, 1994). The individual results were categorized
as ‘‘normal’’ or ‘‘altered’’ and statistical analyses were performed.
The Gaps in Noise (GIN) Test is composed of a series of computer-generated, uniformly distributed, broadband noise
segments (duration, 6 s). Each 6 s segment of noise contains 0–3 silent gaps of varying duration (2–20 ms). The original GIN
Test includes 4 lists of equivalent difficulty; however, 2 lists were used in this study (lists 1 and 3) and were allocated
randomly (1 list to each ear) to each subject, according the method described in a Brazilian study (Samelli & Schochat, 2008).
In a practice session, listeners were instructed to press the response button as soon as they heard a gap. Not pressing the
response button when a gap occurred was considered an error (Musiek et al., 2005). A normal GIN Test result was defined as a
threshold of 5 ms for listeners aged 10–17.92 years (i.e., 10 years 0 months–17 years 11 months) (Perez & Pereira, 2010) and
4 ms for listeners aged 18 years (Samelli & Schochat, 2008). The individual results were categorized as ‘‘normal’’ or
‘‘altered’’ and statistical analyses were performed.
The test stimuli (for the FP, DP, and GIN Tests) were administered using a clinical audiometer (Beta Medical) with TDH-39
earphones and were presented at a sensation level of 50 dB (the sensation level was in reference to the pure-tone audiogram
mean of 0.5, 1, and 2 kHz). For SVM and SNVM, the stimuli were presented in an open field.
2.4. Language evaluation
Language abilities were assessed using validated tests of phonological and syntactic awareness.
The Phonological Awareness Test provides an indicator of the ability to perceive and manipulate speech sounds, and
consists of several subtests that measure a wide variety of phonological awareness abilities, including blending syllables,
phoneme blending, rhyming, phoneme segmentation, phoneme deletion, and phoneme transposition. The outcome measure
used in this study was the addition of points of each subtest. Normal phonological scores were defined as 29 points (Santos
& Pereira, 1997).
The Syntactic Awareness Test was administered using judgment, correction, and categorization tasks. For Task 1—
Grammar judgment, the participant was asked to listen to 20 sentences and was required to decide whether or not each
sentence was grammatically correct. For Task 2—Grammatical correction, the participant was asked to listen to 10 sentences
and was required to correct the mistakes. For Task 3—Grammatical correction of incorrect grammar and semantics, the
participant was also asked to listen to 10 sentences and was required to correct the grammatical errors without altering any
semantic errors. In Task 4—Categorization of words, the participant was required to categorize 15 words as verbs, adjectives,
or nouns. The standard used to define normal responses was based on the education level of each participant (Capovilla &
Capovilla, 2006).
2.5. Statistical analyses
All analyses were performed using SPSS (version 19, IBM, Armonk, NY USA). A Mann–Whitney test was conducted to
compare the performance of both groups on the SVM and SNVM tests that had non-normal distribution. Fisher’s exact test
was used to determine the association between the categorical variables of the tests: PF, PD, and GIN. Pearson’s correlations
were calculated to explore possible associations between auditory temporal processing and language. Statistical significance
was set at P < 0.05.
3. Results
3.1. Peripheral and central auditory findings
Peripheral auditory status was similar between the NF1 and control groups, and all participants had normal acoustic
hearing. Table 2 shows the mean pure-tone air-conduction thresholds for the 2 groups. Correct scores for the SVM and SNVM
tests are summarized in Table 3. Based on an analysis of performance on each measure of these tests, the NF1 group scored
significantly lower than the control. Table 4 shows the quantitative data from FP, DP, and GIN Tests that presented a
significant difference between the groups evaluated. These data demonstrated that patients with NF1 had abnormal
temporal processing (ordering and resolution disabilities).
3.2. Language findings
As shown in Table 5, significant differences between groups were detected for phoneme blending, rhyming, phoneme
segmentation, phoneme deletion, and phoneme transposition. The phonological processing abilities observed in patients
with NF1 patients were lower than expected for their ages. The results of Pearson’s correlation demonstrated the presence of
positive correlations between the phonological awareness test and FP humming (r = 0.560, P = 0.001), FP labeling (r = 0.415,
P = 0.022) and DP humming (r = 0.569, P = 0.001).
Table 6 shows the categorized results of the Syntactic Awareness Test (in %) for the NF1 and control groups. These results
showed that patients with NF1 performed well in the tasks that required syntactic awareness abilities, but their performance
was significantly lower than that of the control group in grammar judgment, grammar correction, grammar correction of
incorrect grammar and semantics, and word categorization.
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
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Table 2
Peripheral auditory characteristics of the subject populations evaluated.
Variable
Group
P value
NF1
Control
RE
PTA (0.25, 0.5, 1 kHz)
Mean
Range
SD
PTA (2, 4, 8 kHz)
Mean
Range
SD
LE
RE
LE
16.80
5–25
6.90
16.40
5–25
6.10
14.80
0–25
6.69
14.20
0–25
6.56
0.1642
0.4392
18.00
10–25
5.11
18.60
10–25
5.59
15.40
5–25
6.44
15.80
5–25
6.72
0.1679
0.4656
LE, left ear; PTA, pure tone average; RE, right ear; SD, standard deviation; NF1, neurofibromatosis type 1.
Table 3
Summary of the results of the Sequential Verbal Memory and Sequential Non-Verbal Memory Tests.
Test
Group
N
Mean (no. of correct responses)
SD
Minimum
Median
Maximum
P value
SVM
NF1
Control
25
22
2.20
2.82
0.91
0.39
0
2
2
3
3
3
0.009*
SNVM
NF1
Control
25
22
2.36
2.77
0.70
0.42
1
2
2
3
3
3
0.028*
N, number; SD, standard deviation; SVM, Sequential Verbal Memory Test; SNVM, Sequential Non-Verbal Memory Test; NF1, neurofibromatosis type 1.
* Statistically significant difference.
Table 4
Summary of the results of the Frequency Patterns, Duration Patterns, and Gaps in Noise Tests.
Normal
Altered
P value
FP Humming
FP Labeling
DP Humming
DP Labeling
NF1
Control
NF1
Control
NF1
Control
NF1
Control
NF1
GIN
Control
4
21
0.001*
14
8
2
23
0.001*
12
10
0
25
0.000*
14
8
1
24
0.000*
14
8
0
25
0.000*
16
6
FP, Frequency Patterns Test; DP, Duration Patterns Test; GIN, Gaps in Noise Test; NF1, neurofibromatosis type 1; Normal, the values fell within the normal
range for the test; Altered, the values fell outside the normal range for the test.
* Statistically significant difference.
4. Discussion
The results of the present study support our hypotheses that NF1 patients have APD in the absence of peripheral hearing
problems. Furthermore, APD was correlated with language disabilities, as described previously in a patient with NF1 (Batista
et al., 2010).
The poor results observed in the SVM and SNVM confirmed the presence of a temporal ordering deficit in NF1 patients.
Some studies have indicated that this deficit in temporal ordering can result in poor organization skills, such as poor note
taking and assignment completion skills, poor general sequencing, difficulty in following directions and instructions, and
poor spelling and writing skills, especially when attempting to write from dictation (Bellis, 2003; Pereira & Schochat, 1997).
The poor performance of NF1 patients with respect to temporal ordering may be correlated with some CNS findings: areas
of high signal intensity on nuclear magnetic resonance, which are found in the brainstem pathways and cortex of 43–79% of
patients with NF1; abnormal inferior frontal and Heschl gyri; and an enlarged posterior midbody of the corpus callosum. All
of these structures are required for effective sequential information processing and organization (Billingsley et al., 2003;
Hyman, Gill, Shores, Steinberg, & North, 2007; Lopes et al., 2008; Pride et al., 2010).
Data analysis also revealed significantly lower scores in FP and DP in the NF1 group, indicating a deficit in processing the
acoustic patterns that underlies a melodic contour. Prosodic deficits may cause difficulty in extracting key words from
spoken messages, which may cause the listener to be unable to discriminate subtle differences in meaning brought about by
changes in relative vocal stressing and intonation. In addition, individuals with prosodic deficits can have difficulty
perceiving jokes and sarcasm, and may be somewhat monotonic in their own speech (Bellis, 2003).
Using the GIN Test, a deficit in temporal resolution was confirmed in all patients with NF1. Temporal resolution is the
ability to follow rapid changes in the envelope of an auditory stimulus over time (Musiek et al., 2005). Past research using
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
j.jcomdis.2013.12.002
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Table 5
Results of the phonological awareness test.
Subtest
Group
N
Mean
SD
Minimum
Median
Maximum
P value
Blending syllables
NF1
Control
25
22
5
5
0
0
5
5
5
5
5
5
1
Phoneme blending
NF1
Control
25
22
2.360
4.590
1.729
0.666
0
3
2
5
5
5
0.000*
Rhyming
NF1
Control
25
22
2.960
4.360
1.207
0.790
1
2
3
4.5
5
5
0.000*
Phoneme segmentation
NF1
Control
25
22
1.080
4.500
1.706
0.802
0
2
0
5
5
5
0.000*
Phoneme deletion
NF1
Control
25
22
2.720
4.230
1.860
0.869
0
3
3
4.5
5
5
0.004*
Phoneme transposition
NF1
Control
25
22
2.160
4.730
1.748
0.631
0
3
2
5
5
5
0.000*
Score final
NF1
Control
25
22
16.280
24.410
6.380
2.538
8
20
16
29
29
30
0.000*
NF1, neurofibromatosis type 1; N, number; SD, standard deviation.
* Statistically significant difference.
Table 6
Results of the Syntactic Awareness Test.
Subtest
Categorization
Groups
P value
NF1
Control
N
(%)
N
(%)
0
0
100
0.004*
Grammar judgment
Very low
Low
Mean
1
7
17
4
28
68
0
0
22
Grammar correction
Very low
Low
Mean
High
1
1
12
11
4
4
48
44
0
0
5
17
0
0
22.7
77.3
0.017*
Grammar correction for incorrect grammar and semantics
Very low
Low
Mean
High
2
2
18
3
8
8
72
12
0
0
13
9
0
0
59.1
40.9
0.007*
Categorization of words
Very low
Low
Mean
High
2
2
15
6
8
8
60
24
0
0
3
19
0
0
13.6
86.4
0.000*
Final classification
Very low
Low
Mean
High
1
4
16
4
4
16
64
16
0
0
5
17
0
0
22.7
77.3
0.000*
NF1, neurofibromatosis type 1; N, number; (%), percentage.
* Statistically significant difference.
patients with neurological lesions demonstrated that the difficulty in processing temporal auditory characteristics may
reside in the neurons that are responsible for the synchronous transmission of stimuli, causing changes in neuronal firing and
compromising the ability of the auditory system to resolve temporal tasks (Bamiou et al., 2006). However, to date, this
abnormality has not been described in NF1 patients.
Disorders in temporal resolution are an indication that the individual is unable to perceive fast changes in speech. In NF1,
this disorder might be associated with a deficiency in the production of neurofibromin in the nervous system. Neurofibromin
plays an important role in the cell transduction involved in synaptic signaling, and neurofibromin deficiency in patients with
NF1 can reduce the amount of effective synaptic connections, resulting in losses in temporal resolution abilities (Johnston,
2003).
NF1 patients had a poor performance in the tasks that required syntactic and phonological abilities. Phonological
awareness is the area of oral language that relates to the ability to think about the sounds in a word (the word’s phonological
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
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7
structure) rather than just the meaning of the word. Billingsley et al. (2003) used functional imaging to compare 15 NF1
children with 15 unaffected children during phonological tasks. Those authors concluded that increased participation of the
right hemisphere during the auditory phonology task may reflects NF1 white matter ‘‘disconnectivity’’ between frontal and
posterior areas. In another study, Watt, Shores, and North (2008) examined systematically the phonological and reading
abilities of 30 NF1 children and highlighted a prevalence of phonological difficulties in 75% of that population. These results
shed light on the previous report of an NF1 patient, who showed severe difficulties in rhyming, phoneme segmentation,
phoneme deletion, and phoneme transpositions tasks (Batista et al., 2010).
In this study, a strong relationship was found between temporal processing tests (FP and DP) and phonological
awareness. A link between temporal processing and phonological awareness had been established previously in different
populations (Cacace, McFarland, Ouimet, Schrieber, & Marro, 2000; Capellini, Germano, & Cardoso, 2008; Engelmann &
Ferreira, 2009; Furbeta, del, & de Felippe, 2005; Miller & Wagstaff, 2011; Oliveira, Cardoso, & Capellini, 2011; Pinheiro,
Oliveira, Cardoso, & Capellini, 2010; Zaidan & Baran, 2013). Phonological awareness involves primary (low-level) and
secondary (high-level) skills. The primary level (phonological sensitivity) relies strongly on sensitivity to speech sounds and
depends on acoustic features. Problems in the primary level carry forward and result in difficulties in the secondary level
(phonological awareness), which is responsible for the isolation, segmentation, and manipulation of phonemic units (Plaza,
2001). This hypothesis may explain the results found in the present study. However, further studies are needed to replicate
and extend the current findings, and to identify the specific pathway that underlies this abnormality.
5. Conclusions
The findings of the present study suggest that NF1 patients have an auditory temporal processing disorder, as evidenced
in behavioral auditory processing tests. This disorder was correlated with the language deficits associated with NF1. The
present results may contribute to a more appropriate care of patients with NF1 and remediation of auditory processing
deficits by using auditory training, environmental modifications, and academic management.
Author contributions
Pollyanna Barros Batista: Design and conceptualization of the study; data collection, analysis, and interpretation;
manuscript drafting and revision. Stela Maris Aguiar Lemos: Study design; data interpretation; manuscript revision. Luiz
Oswaldo Carneiro Rodrigues: Medical patient supervision; study design; data interpretation; manuscript revision. Nilton Alves
de Rezende: Medical patient supervision; design and conceptualization of the study; analysis and interpretation of the data;
manuscript revision.
Conflict of interest statement
The authors reported no conflicts of interest with the research described in this article.
Acknowledgments
This work was supported by CNPq, FAPEMIG [APQ-00928-11], Universidade Federal de Minas Gerais (UFMG), and PróReitoria de Pesquisa da UFMG. PBB was supported by a fellowship from CAPES.
Appendix A. Continuing education
CEU questions:
(1) What complications are not associated with NF1?
a. Cognitive impairment and learning disabilities
b. Deformation of bone structure and iris Lisch nodules
c. Visual impairment due to Lisch nodules and malignant transformation of CAL spot in skin tumors
d. Optic pathway glioma and café au lait spots
(2) The present study provided evidence that patients with NF1 have phonological awareness disabilities that do not
include:
a. Rhyming
b. Blending syllables
c. Phoneme blending
d. Phoneme segmentation
(3) The results of correlation analysis between auditory temporal and language tests demonstrated:
a. Positive correlations between the Phonological Awareness test and FD humming, FP labeling, and DP humming
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
j.jcomdis.2013.12.002
G Model
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8
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b. Positive correlations between the Syntactic Awareness test and FP humming and FP labeling
c. Positive correlations between Phonological and Syntactic Awareness tests and FP humming and FP labeling
d. No correlations were observed
(4) The analysis of auditory temporal tests in the NF1 patients included in this study revealed:
a. Deficit in temporal ordering, deficit in processing the acoustic patterns, and deficit in temporal resolution
b. Auditory decoding deficit, deficit in processing the acoustic patterns, and deficit in temporal resolution
c. Auditory integration deficit, deficit in processing the acoustic patterns, and deficit in temporal resolution
d. Auditory tolerance-fading memory and deficit in temporal resolution
(5) The deficits in temporal resolution observed in patients with NF1 can be associated with a deficiency of neurofibromin in
the nervous system that reduces the amount of effective synaptic connections.
a. True
b. False
References
American Speech-Language-Hearing Association. (1996). Central auditory processing: Current status and implications for clinical practice. American Journal of
Audiology, 5, 41–54.
American Speech-Language-Hearing Association. (2005). (Central) Auditory Processing Disorders [Technical Report] [cited 2013 March 12]. [Internet] Available from:
http://www.asha.org/docs/pdf/TR2005-00043.pdf.
Bamiou, D. E., Musiek, F. E., Stow, I., Stevens, J., Cipolatti, L., Brown, M. M., et al. (2006). Auditory temporal processing deficits in patients with insular stroke.
Neurology, 67, 614–619.
Batista, P. B., Silva, C. M., Valentim, H. O., Rodrigues, L. O. C., & Rezende, N. A. (2010). Avaliação do processamento auditivo na Neurofibromatose tipo 1. Revista da
Sociedade Brasileira de Fonoaudiologia, 15, 604–608.
Bellis, T. J. (2003). Assessment and management of central auditory processing disorders in the educational setting: From science to practice. New York: Thomson
Delmar Learning.
Billingsley, R. L., Jackson, E. F., Slopis, J. M., Swank, P. R., Mahankali, S., & Moore, B. D. (2003). Functional magnetic resonance imaging of phonologic processing in
neurofibromatosis 1. Journal of Child Neurology, 18, 732–740.
Cacace, A. T., McFarland, D. J., Ouimet, J. R., Schrieber, E. D., & Marro, P. (2000). Temporal processing deficits in remediation-resistant reading-impaired children.
Audiology and Neurotology, 5, 83–97.
Capellini, S. A., Germano, G. D., & Cardoso, A. C. V. (2008). Relação entre habilidades auditivas e fonológicas em crianças com dislexia do desenvolvimento.
Psicologia Escolar e Educacional, 12, 235–251.
Capovilla, A. G. S., & Capovilla, F. C. (2006). Avaliando a habilidade metassintática por meio da prova de consciência sintática. In F. C. Capovilla & A. G. S. Capovilla
(Eds.), Prova de consciência sintática (PCS): normatizada e validada para avaliar a habilidade metassintática de escolares de 1 a 4 séries do ensino fundamental (pp.
14–24). São Paulo: Memnon.
Corona, A. P., Pereira, L. D., Ferrita, S., & Rossi, A. G. (2005). Memória Sequencial Verbal de três a quatro sı́labas em escolares. Pró-Fono, 17, 27–36.
Coudé, F. X., Mignot, C., Lyonnet, S., & Munnich, A. (2006). Academic impairment is the most frequent complication of neurofibromatosis type-1(NF1) in children.
Behavior Genetics, 36, 660–664.
Engelmann, L., & Ferreira, M. I. D. C. (2009). Avaliação do processamento auditivo em crianças com dificuldades de aprendizagem. Revista da Sociedade Brasileira de
Fonoaudiologia, 14, 69–74.
Feldkamp, M. M., Gutmann, D. H., & Guha, A. (1998). Neurofibromatosis type 1: Piecing the puzzle together. Canadian Journal of Neurological Sciences, 25, 181–191.
Ferner, R. E., Hughes, R. A. C., & Weinman, J. (1996). Intellectual impairment in neurofibromatosis. Journal of the Neurological Science, 138, 125–133.
Friedman, J. M. (1999). Epidemiology of neurofibromatosis type 1. American Journal of Medical Genetics, 89, 1–6.
Furbeta, T., del, C., & de Felippe, A. C. (2005). Avaliação simplificada do processamento auditivo e dificuldades de leitura-escrita. Pró fono, 17, 11–18.
Hirsh, I. J. (1959). Auditory perception of temporal order. Journal of the Acoustical Society of America, 31, 759–767.
Hyman, S. L., Shores, A., & North, K. N. (2005). The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology, 65, 1037–1044.
Hyman, S. L., Gill, D. S., Shores, E. A., Steinberg, A., & North, K. N. (2007). T2 hyperintensities in children with neuroflbromatosis type 1 and their relationship to
cognitive functioning. Journal of Neurology, Neurosurgery & Psychiatry, 78, 1088–1091.
Johnston, M. V. (2003). Brain plasticity in paediatric neurology. European Journal of Paediatric Neurology, 7, 105–113.
Johnston, M. V. (2004). Clinical disorders of brain plasticity. Brain & Development, 26, 73–80.
Lammert, M., Friedman, J. M., Kluwe, L., & Mautner, V. F. (2005). Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Archives of
Dermatology, 141, 71–74.
Ledbetter, D. H., Rich, D. C., O’Connell, P., Leppert, M., & Carey, J. C. (1989). Precise localization of NF1 to 17q11.2 by balanced translocation. American Journal of
Human Genetics, 44, 20–24.
Lee, M. J., & Stephenson, D. A. (2007). Recent developments in neurofibromatosis type 1. Current Opinion in Neurology, 20, 135–141.
Lopes, F. F. J. R. , Munis, M. P., Soares, S. A., Sanches, R. A., Goloni-Bertollo, E. M., & Pavarino-Bertelli, E. C. (2008). Unidentified bright objects on brain MRI in children
as a diagnostic criterion for neurofibromatosis type 1. Pediatric Radiology, 38, 305–310.
Lorch, M., Ferner, R., Golding, J., & Whurr, R. (1999). The nature of speech and language impairment in adults with neurofibromatosis 1. Journal of Neurolinguistics,
12, 157–165.
Miller, C. A., & Wagstaff, D. A. (2011). Behavioral profiles associated with auditory processing disorder and specific language impairment. Journal of Communication
Disorders, 44, 745–763.
Mody, M. (2003). Rapid auditory processing deficits in dyslexia: A commentary on two differing views. Journal of Phonetics, 31, 529–539.
Moore, B. C. J. (2003). An introduction to the psychology of hearing (5th ed., pp. 163–). Amsterdam: Academic Press.
Musiek, F. E. (1994). Frequency (pitch) and duration pattern tests. Journal of the American Academy of Audiology, 5, 265–268.
Musiek, F. E., Shinn, J. B., Jirsa, R., Bamiou, D. E., Baran, J. A., & Zaida, E. (2005). GIN (Gaps-in-Noise) test performance in subjects with and without confirmed central
auditory nervous system involvement. Ear and Hearing, 26, 608–618.
National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. (1988). Archives of Neurology, 45, 575–578.
Oliveira, A. M., Cardoso, A. C. V., & Capellini, S. A. (2011). Desempenho de escolares com distúrbio de aprendizagem e dislexia em testes de processamento auditivo.
Revista CEFAC, 13, 513–521.
Pereira, L. D. (1996). Identificação da Desordem do Processamento Auditivo Central através de observação comportamental—Organização de procedimentos
padronizados. In E. Schochat (Ed.), Processamento Auditivo (1st ed., pp. 43–56). São Paulo: Lovise.
Pereira, L. D., & Schochat, E. (1997). Processamento auditivo central: manual de avaliação. São Paulo: Lovise.
Perez, A. P., & Pereira, L. D. (2010). O teste gap in noise em crianças de 11 e 12 anos. Pró Fono, 22, 7–12.
Pikus, A. T. (1995). Pediatric audiologic profile in type 1 and type 2 neurofibromatosis. Journal of the American Academy of Audiology, 6, 54–62.
Pinheiro, M. L., & Musiek, F. E. (1985). Assessment of central auditory dysfunction: Foundation and clinical correlates. Baltimore: Williams & Wilkins.
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
j.jcomdis.2013.12.002
G Model
JCD-5647; No. of Pages 9
P.B. Batista et al. / Journal of Communication Disorders xxx (2014) xxx–xxx
9
Pinheiro, F. H., Oliveira, A. M., Cardoso, A. C. V., & Capellini, S. A. (2010). Testes de escuta dicótica em escolares com distúrbio de aprendizagem. Brazilian Journal of
Otorhinolaryngology, 76, 257–262.
Plaza, M. (2001). The interaction between phonological processing, syntactic awareness and reading: Longitudinal study from kindergarten to grade 1. First
Language, 21, 3–24.
Poissant, S. F., Megerian, C. A., & Hume, D. (2003). Cochlear implantation in a patient with neurofibromatosis type 1 and profound hearing loss: Evidence to support
a cochlear site of lesion. American Otological Society, 24, 751–756.
Pride, N., Payne, J. M., Webster, R., Shores, E. A., Rae, C., & North, K. N. (2010). Corpus callosum morphology and its relationship to cognitive function in
neurofibromatosis type 1. Journal of Child Neurology, 25, 834–841.
Samelli, A. G., & Schochat, E. (2008). The gaps-in-noise test: Gap detection thresholds in normal-hearing young adults. International Journal of Audiology, 7, 238–
245.
Santos, M. T. M., & Pereira, L. D. (1997). Consciência fonológica. In L. D. Pereira & E. Schochat (Eds.), Processamento auditivo central: manual de avaliação. São Paulo:
Lovise.
Souza, J. F., Toledo, L. L., Ferreira, M. C. M., Rodrigues, L. O. C., & Rezende, N. A. (2009). Neurofibromatose tipo 1: mais comum e grave do que se imagina. Revista da
Associação Medica Brasileira, 55, 394–399.
Tallal, P. (1980). Auditory temporal perception, phonics and reading disabilities in children. Brain and Language, 9, 182–198.
Tonsgard, J. E. (2006). Clinical manifestations and management of neurofibromatosis Type 1. Seminars in Pediatric Neurology, 13, 2–7.
Viemeister, N., & Plack, C. J. (1993). Time analysis. In W. A. Yost, A. N. Popper, & R. R. Fay (Eds.), Human Psychophysics (pp. 116–154). New York: Springer-Verlag.
Viskochil, D., Buchberg, A. M., Xu, G., Cawthon, R. M., Stevens, J., Wolff, R. K., et al. (1990). Deletions and a translocation interrupt a cloned gene at the
neurofibromatosis type 1 locus. Cell, 62, 187–192.
Wallace, M. R., Marchuk, D. A., Andersen, L. B., Letcher, R., Odeh, H. M., Saulino, A. M., et al. (1990). Type 1 neurofibromatosis gene: Identification of a large
transcript disrupted in three NF1 patients. Science, 249, 181–186.
Watt, S. E., Shores, A., & North, K. N. (2008). An examination of lexical and sub-lexical reading skills in children with neurofibromatosis type 1. Child
Neuropsychology, 14, 401–418.
Zaidan, E., & Baran, J. A. (2013). Gaps-in-noise (GIN) test results in children with and without reading disabilities and phonological processing deficits.
International Journal of Audiology, 52, 113–123.
Please cite this article in press as: Batista, P. B., et al. Auditory temporal processing deficits and language disorders in
patients with neurofibromatosis type 1. Journal of Communication Disorders (2014), http://dx.doi.org/10.1016/
j.jcomdis.2013.12.002