Developmental Science 8:1 (2005), pp 36– 43
REPORT
Blackwell Publishing, Ltd.
Maladaptive conflict monitoring as evidence for executive
dysfunction in children with chromosome 22q11.2 deletion
syndrome
Joel P. Bish,1 Samantha M. Ferrante,1 Donna McDonald-McGinn,1
Elaine Zackai1 and Tony J. Simon1, 2
1. Children’s Hospital of Philadelphia, USA
2. University of Pennsylvania, USA
Abstract
Using an adaptation of the Attentional Networks Test, we investigated aspects of executive control in children with chromosome
22q11.2 deletion syndrome (DS22q11.2), a common but not well understood disorder that produces non-verbal cognitive deficits
and a marked incidence of psychopathology. The data revealed that children with DS22q11.2 demonstrated greater difficulty
than controls in locating and processing target items in the presence of distracters. Importantly, children with DS22q11.2 showed
a deficit in the ability to monitor and adapt to stimulus conflict. These data provide evidence of inadequate conflict adaptation
in children with DS22q11.2, a problem that is also present in schizophrenia. The findings of specific executive dysfunction in
this group may provide a linkage between particular genetic abnormalities and the development of psychopathology.
Chromosome 22q11.2 deletion syndrome (DS22q11.2)
is a recently defined syndrome (Dunham et al., 1999)
that encompasses DiGeorge (DiGeorge, 1965) and
Velocardiofacial syndromes (Shprintzen et al., 1978). It
is a congenital condition resulting from a 3 Mb deletion
of the long (q) arm of chromosome 22 and has an estimated prevalence of at least 1 in 4000 live births (Burn
& Goodship, 1996). The commonly observed manifestations of DS22q11.2 include cleft palate, heart defects,
T-cell abnormalities, neonatal hypocalcemia, facial dysmorphisms, in addition to mild to moderate cognitive
deficits (Bingham et al., 1997). The cognitive deficits
demonstrated in DS22q11.2 include an overall delay in
cognitive, psychomotor and language development and
an overall IQ in the range of 70–85 (Gerdes et al., 1999;
Moss et al., 1999; Swillen, Vogels, Devriendt & Fryns,
2000; Wang, Woodin, Kreps-Falk & Moss, 2000). In
addition to the cognitive deficits, children with DS22q11.2
show an extremely high incidence of psychopathology,
especially schizophrenia, as they reach adulthood. It
is estimated that around 30% of all children with
DS22q11.2 will develop a schizophrenia spectrum
disorder (Feinstein, Eliez, Blasey & Reiss, 2002).
Deficits in the areas of visuospatial and numerical
performance have also been recently reported (Bearden
et al., 2001; Simon, Bearden, McDonald-McGinn &
Zackai, 2005). Using common neuropsychological tests,
Bearden et al. (2001) showed selective deficits in visualspatial memory, with relative preservation of verbal functioning and object memory. Additionally, recent reports
of executive dysfunction in this syndrome (Woodin et al.,
2001; Sobin et al., 2004) may provide a link between
behavioral performance on neuropsychological and
cognitive tests and the development of psychopathology.
Relationships between the catechol o-methyltransferase
(COMT) genotype, a gene directly affected in DS22q11.2
by virtue of the deletion of one copy, and executive function have been reported (Bearden et al., in press) and
may help to determine the course of the development of
disinhibitory pathologies (schizophrenia, ADHD) in
certain subsets of this population. Interestingly, the
COMT genotype has also been directly associated with
executive functions as implemented in the dorsolateral
prefrontal cortex of schizophrenics (Egan et al., 2001).
Our current research is aimed at extending the domain
specific findings of visuo-spatial and executive dysfunction
Address for correspondence: Dr Joel P. Bish, Children’s Hospital of Philadelphia, 3535 Market Street, Philadelphia, PA 19104, USA; e-mail:
bish@email.chop.edu
© Blackwell Publishing Ltd. 2005, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148, USA.
Attentional dysfunction and 22q11.2
in this population. Our method is to use cognitive processing tasks designed to directly interrogate the neural
structures underlying the functional deficits shown in
this group. We recently reported deficits in spatial orienting, enumeration and magnitude comparison in children
with DS22q11.2 (Simon et al., in press). These tasks
were selected because each would be predicted to systematically involve a characteristic pattern of performance that is dependent on the posterior parietal lobe
(PPL) to a greater or lesser extent. The results would then
enable us to evaluate our hypothesis that PPL dysfunction is a major cause of the visuospatial and numerical
cognitive deficits seen in DS22q11.2. The children with
DS22q11.2 showed systematic difficulties in all three
tasks, demonstrating a graded performance based on the
amount of involvement of the posterior parietal lobe.
The purpose of the present study is to further
investigate the nature of executive control dysfunction
manifested by children with DS22q11.2 with hopes of
providing potential behavioral markers of the development of psychopathology. For example, affected children
with increased executive control dysfunctions in addition
to other factors may be those that have an increased risk
for psychopathology later in life. Posner and Petersen
(1990) originally proposed that attentional function
could be segregated into the sub-functions of alerting,
orienting and executive control. Alerting is characterized
as maintaining an alert state over time and has been
associated with the norepinephrine system of the right
frontal and parietal lobes (Coull, Frith, Frackowiak &
Grasby, 1996). Orienting refers to the ability to use spatial cues to selectively attend to a particular location in
the visual field and has been associated with activity in the
superior parietal lobule, the temporal–parietal junction
(e.g. Corbetta, Kincade, Ollinger, McAvoy & Shulman,
2000), frontal eye fields (e.g. Hopfinger, Buonocore &
Mangun, 2000), superior colliculus (e.g. Mesulam, 1981),
and the pulvinar nucleus of the thalamus (e.g. Petersen,
Robinson & Morris, 1987). Executive control includes
the ability to monitor and adapt to conflict within the
stimulus–response environment through inhibition and
involves functional activation of the anterior cingulate and
the dorso-lateral prefrontal cortex (Bush, Luu & Posner,
2000; MacDonald, Cohen, Stenger & Carter, 2000;
Botvinick, Nystrom, Fissell, Carter & Cohen, 1999).
Operation of this system has been associated with dopaminergic genes such as COMT (Fosella et al., 2002), one
copy of which is deleted in individuals with DS22q11.2.
In order to investigate the executive control network
and its interaction with the attentional orienting system
in children with DS22q11.2, we used an adaptation of the
Attentional Network Test (ANT) that had previously
been altered for use with children (Fan, McCandliss,
© Blackwell Publishing Ltd. 2005
37
Sommer, Raz & Posner, 2002). The ANT is an elegantly
designed, simple task that independently tests the three
previously mentioned attentional functions. The ANT
is a combination of a spatial cueing response time task
(Posner, 1980) and a flanker task (Eriksen & Eriksen, 1974)
and requires participants to identify the directional
heading (left or right) of a specific target. In our version
of the task, participants are presented with four spatial
cues types (none, valid, neutral and invalid) that may
or may not draw attention to the spatial location of a
subsequently appearing target. The comparison of trials
with neutral and no cues provides an index of the alerting network. This is because trials including a neutral
cue should provide an alerting benefit compared to trials
without a cue in which the target itself produces an alerting response. Comparison of trials with valid spatial
cues and those with neutral cues provides an index of
the ability to use spatial cues to ‘orient’ attention to the
appropriate location in space prior to the onset of the
target. The orienting network can also be evaluated
through the comparison of invalid versus neutral or
valid cues. The addition of the invalid cue condition in
our version of the task was intended to enable further
investigation of our previous findings. Those data demonstrated selective deficits in children with DS22q11.2 in
disengaging attentional resources from an inappropriately cued location (Simon et al., 2005).
The ANT also includes three flanker conditions that
evaluate the executive network previously described. The
flanker conditions refer to the presence and type of irrelevant flankers on both sides of the target stimulus. The
target can be accompanied by no flankers (i.e. appear by
itself ), by congruent flankers (i.e. ones pointing in the
same direction as the target), or by incongruent flankers
(i.e. ones pointing in the opposite direction to the target).
Incongruent flankers require greater inhibition of irrelevant information than do congruent flankers. It has been
shown that individuals with executive control deficits
experience increased difficulty in processing incongruent
flankers compared to congruent flankers (Crone, Jennings
& van der Molen, 2003).
Based on previous findings of executive function
deficits (Woodin et al., 2001; Bearden et al., in press;
Sobin et al., 2004), we hypothesized that children with
DS22q11.2 would demonstrate dysfunctional executive
control. By comparing conditions with congruent versus
incongruent flankers, we could evaluate a child’s ability
to focus attention on a specific target location without
suffering the adverse effects of processing the conflicting
flankers. We could also measure dynamic conflict monitoring and adaptation by examining the Gratton effect
(Gratton, Coles & Donchin, 1992). The Gratton effect
describes a pattern of performance in which processing
38
Joel P. Bish et al.
of congruent trials improves when preceded by congruent trials relative to when preceded by incongruent
trials. Additionally, performance on incongruent trials is
improved when preceded by an incongruent trial relative
to when preceded by a congruent trial. These findings
are interpreted to indicate that the previous trial has set
up the conflict context for the following trial. Specifically, the anterior cingulate is postulated to continuously
monitor for conflict in the environment and invoke the
dorso-lateral prefrontal cortex to inhibit non-target
stimuli when conflict is present (Botvinick et al., 1999).
Additionally, the posterior parietal lobe is presumed
to participate in altering the focus of spatial attention
(Casey et al., 2000). In addition to our predictions
regarding executive function, we hypothesized that
children with DS22q11.2 would demonstrate difficulties
with the cueing portion of the task, specifically the
invalid cue condition, because of its reliance on the
posterior parietal lobe. Since we know of no relevant
data, we made no specific predictions based on the alerting aspect of the ANT.
Method
Participants
Thirty-four children completed the ANT. Of the 34, 16
were typically developing children and 18 were children
diagnosed with chromosome 22q11.2 deletion syndrome.
Diagnosis was confirmed through the use of fluorescence
in situ hybridization (FISH) test. The typically developing children had a mean age of 9 years, 7 months (SD =
1.8 years, range = 7–14 years) and consisted of seven
females and nine males. The children with DS22q11.2 had
a mean age of 9 years, 2 months (SD = 1.7 years, range =
7–14 years) and consisted of 12 females and six males.
Design and procedure
The 34 participants in this study were administered an
adaptation of the ANT as part of a large battery of
cognitive and neuropsychological tests. In our version of
the child-based ANT (see Fan et al., 2002, for original
task description), the child was required to locate and
identify the orientation (left or right) of a friendly alien
spaceship. The target was a small alien pictured in a
spaceship on the side of which an arrow pointed in
the same direction as the spaceship. The children were
instructed to focus only on the central spaceship, which
appeared immediately above or immediately below the
fixation cross. When the target appeared (with or without flankers) the child’s task was use the button box
© Blackwell Publishing Ltd. 2005
provided and to push the left button if the spaceship
pointed left and the right button if it pointed right. The
targets were presented within the context of a total of
12 possible trial types integrating four cue types and
three flanker types.
The specific details of trial timing, order and stimulus
size in our version of the ANT were similar to the previously published child version (Fan et al., 2002). On
each trial, the participant was presented with a central
fixation cross for between 400 and 1600 ms in steps of
200 ms. Following this duration, a blank screen was
presented for 50 ms followed by one of four cue types
(none, valid, neutral, or invalid). The cue remained on
the screen for 400 ms followed by another blank screen
for 100 ms. Following this, the target was presented for
3000 ms or until the participant responded. Targets
were presented 1.06 degrees of visual angle above or
below the central fixation point at equal probabilities.
For the No Cue condition, the fixation, in the absence
of a cue, remained on the screen until the presentation
of the target. In the valid Cue condition, an asterisk,
subtending approximately 1 degree of visual angle,
was presented in the exact location of the subsequently
appearing target, either above or below the fixation
cross. In the Neutral Cue condition, an asterisk was
presented in the central location of the fixation cross,
thereby providing no useful spatial information regarding the future location of the target. In the Invalid Cue
condition, which had been added in our version of the
task, the asterisk was presented in the opposite target
location to the following target (i.e. cue is above fixation
and target appears below fixation). The Valid Cue
condition occurred on 75% of the trials with a spatially
useful cue (i.e. valid or invalid but not neutral).
The targets were presented either without flankers
(single) or with flankers (congruent or incongruent). The
flankers were identical to the target stimulus and in the
Congruent condition pointed in the same direction as
the target and in the Incongruent condition pointed in
the opposite direction of the target. The three flanker
types were equally distributed across all cue types.
Prior to the experimental trials, each participant was
presented with 12 demonstration trials, followed by a
24-trial practice block. A total of 144 experimental
trials were randomly presented and lasted no more than
10 minutes. The child was given a short rest midway
through the task.
Results
Data analysis was focused on the overall pattern of
results via evaluation of response time for each condi-
Attentional dysfunction and 22q11.2
tion, the original ANT network indices (e.g. Fan et al.,
2002), and the specific evaluation of the Gratton effect
in children with DS22q11.2. The mean and standard
deviation response time (RT) and mean percentage errors
were calculated for each condition and are presented in
Table 1. Since we were interested in examining potential
executive control differences in children with DS22q11.2,
and since systematically elevated error rates are expected
with executive dysfunction, we evaluated performance
on this task with a combination of response time and
error rates. We first applied accuracy exclusion criteria in
which any subjects performing at or below chance (50%)
on any of the trial conditions were excluded. These
exclusion criteria forced the removal of one individual
with DS22q11.2 from the analyses (52% inaccuracy for
incongruent flankers trials). We then combined the RT
and error rates using the formula RT/(1-%error). This
adjustment is recommended for its consistencies with
traditional views of RT (Townsend & Ashby, 1983), such
as controlling for any speed/accuracy trade-offs and has
been used to examine spatial cueing and executive control in children in the past (Akhtar & Enns, 1989). We
felt it would be particularly appropriate to use when
examining the performance of children with DS22q11.2
since they would be expected to make errors. Excluding
all trials with errors would likely skew the performance
of such children away from a representative characterization of their performance. Using this adjustment, RT
remains unchanged with 100% accuracy and is increased
in proportion with the number of errors.
The adjusted RTs were then evaluated for equality of
variance across groups using Levene’s test for equality of
error variances. Given the significant ( p = .05) increase
in variability within the DS22q11.2 group across a
number of conditions, we then transformed the adjusted
RT’s using the square root for all conditions and retested
them with Levene’s test of equality of variances. At that
point the data met the assumption of equality of variances
39
between groups for all conditions. The transformed
adjusted RT’s were then submitted to a repeated-measures
ANOVA with cue type and flanker type as within-subjects
factors and group as a between-subjects factor.
The main effect of cue type was significant, as expected,
F(3, 29) = 68.732, p < .001, power (.05) = 1.00, with the
valid cue producing the most efficient performance
across groups and flanker types (Figure 1). The main
effect of flanker was also significant, F(2, 30) = 13.879,
p < .001, power (.05) = .996, with the incongruent flankers
producing slower performance for the combined groups
and cue types (Figure 2). The effect of group was statistically significant, F(1, 31) = 4.972, p = .033, power (.05)
= .579, indicating that children with DS22q11.2 were less
efficient across all conditions. The flanker × group interaction was significant, F(2, 30) = 3.508, p = .043, power
(.05) = .610, and inspection of the simple effects revealed
that the children with DS22q11.2 had more difficulty
( p = .05) on trials with incongruent flankers relative to
single and congruent trials when compared to typically
developing children (Figure 2). Neither the cue type ×
group nor the cue type × flanker × group interactions
were significant at the .05 level. These results show a
dysfunction in children with DS22q11.2 related specifically to conditions in which incongruent, distracting
information is presented, and they replicate the findings
of Sobin et al. (2004).
The single indices for the various attentional domains
(e.g. Fosella et al., 2002) were also evaluated, but only the
executive index was near significance. The alerting index
is computed by subtracting the RT of the neutral cue
condition from the no cue condition and was not significantly different between groups t(31) = −.224, p = .824.
For children with DS22q11.2, the mean difference was
29.83 with a standard deviation (SD) of 169.27 and for
the typically developing children, the mean difference
was 19.886 (SD = 54.66). The orienting index is computed by subtracting the RT of the valid cue condition
Table 1 (a) Cueing effect – mean adjusted response time (standard deviation) and mean error rates for controls and DS22q11.2
(b) Flanker effect – mean adjusted response time (standard deviation) and mean error rates for controls and DS22q11.2
(a) Cue type
RT (SD) % errors
DS22q11.2
NC
None
Valid
Neutral
Invalid
1041.76 (377.05) 10.17%
818.96 (170.81) 2.75%
871.29 (357.04) 9.76%
677.57 (127.83) 1.74%
1011.93 (323.64) 9.61%
799.07 (144.88) 2.92%
1020.27 (412.63) 9.63%
789.00 (145.65) 1.04%
(b) Flanker
RT (SD) % errors
DS22q11.2
NC
© Blackwell Publishing Ltd. 2005
Single
Congruent
Incongruent
920.49 (361.11) 7.97%
723.23 (132.72) 2.35%
908.73 (266.15) 6.33%
759.68 (138.89) 1.87%
1129.73 (491.23) 15.09%
830.54 (167.96 ) 2.44%
40
Joel P. Bish et al.
Figure 1 Cueing effect – mean adjusted response time (in ms).
Adjustment = RT/(1-% error).
Figure 2 Flanker effect – mean adjusted response time (in ms).
Adjustment = RT/(1-% error).
from the RT of the neutral cue condition and was not
significant between groups t(31) = −.398, p = .693. Children with DS22q11.2 had a mean difference of 140.64
(SD = 186.81) while typically developing children had a
mean difference of 121.49 (SD = 45.93). The executive
index is calculated by subtracting the congruent flanker
condition from the incongruent flanker condition and
was almost significant between groups t(31) = −2.008,
p = .053. The mean difference for the children with
DS22q11.2 was 220.96 (SD = 294.04) while the mean
difference for controls was 70.86 (SD = 54.42). Again,
these results support the findings of Sobin et al. (2004)
in demonstrating marked deficits in the functioning of the
executive control network in children with DS22q11.2.
To investigate the hypothesis that children with
DS22q11.2 have specific difficulties with conflict mon© Blackwell Publishing Ltd. 2005
Figure 3 Gratton effect – mean unadjusted response time (in
ms). CC = congruent preceded by congruent. IC = congruent
preceded by incongruent. CI = incongruent preceded by
congruent. II = incongruent preceded by incongruent.
itoring, we further evaluated the flanker condition means
by separating them into more specific conditions. To
investigate whether children with DS22q11.2 demonstrate
a typical Gratton effect, we calculated group means for
congruent trials preceded by congruent and incongruent
trials. We also calculated group means for incongruent
trials preceded by congruent and incongruent trials
separately. We then subtracted the mean of congruent–
congruent (CC) trials from the mean of incongruent–
congruent (IC) trials as well as the mean of incongruent
–incongruent (II) trials from congruent–incongruent
(CI) trials. Finally, these difference scores were compared
between groups. Analyses revealed that children with
DS22q11.2 demonstrate a normal Gratton effect for
congruent trials (IC–CC), t(31) = .1.018, p = .318, but
not for incongruent trials (CI–II), t(31) = 2.094, p = .044
(Figure 3). That is, when an incongruent trial follows
an incongruent trial, processing for the children with
DS22q11.2 is handicapped even further and reaction
time increases. This is the opposite pattern to that seen
in typically developing children. The increase in response
time to II trials relative to CI trials in children with
DS22q11.2 thus reflects the inability to efficiently alter
attentional resources based on previous environmental
context. This specific inefficiency, as well as the more
general differences revealed by the results of the ANOVA
and the executive network index, provides direct evidence
of executive dysfunction in children with DS22q11.2.
Discussion
This study demonstrates clear executive function deficits
in children with DS22q11.2. Replicating and extending
the findings of Sobin et al. (2004), the results indicate
Attentional dysfunction and 22q11.2
that, in addition to the general spatial attention deficits
seen in our previous studies (Bearden et al., 2001; Simon
et al., 2005), children with DS22q11.2 have both generalized executive control dysfunction and increased difficulty in dynamically changing the focus of attention to
inhibit the extraneous processing of irrelevant stimuli in
their environment. Based on previous findings, (Botvinick
et al., 1999) one interpretation of these results is that
they arise from dysfunction of the executive control
network, which depends upon the anterior cingulate and
dorsolateral prefrontal cortex. An intriguing alternative
interpretation is that the dysfunction actually arises
from an inability to fine-tune or engage attention to a
specific target location in the presence of distracters (e.g.
Casey et al., 2000). This competence depends upon the
posterior parietal system, which has already been shown
to be dysfunctional under other circumstances (Simon
et al., 2005). The deficits in performance are demonstrated in a number of ways in this data. Most obviously,
the inefficient processing (both slowed RT and increased
error rates) for incongruent trials compared to both
single and congruent trials indicates that children with
DS22q11.2 suffer from distinct difficulty with conflicting
information when visually presented close to the target
stimulus. Additionally, a trend towards an improvement
for congruent flankers in children with DS22q11.2
suggests that all stimuli (conflicting or not) appear to
be encoded and may be influencing their efficiency at
processing and responding to targets. Specifically, the
trend toward a response time benefit shown for congruent stimuli compared to a single stimuli suggests that
children with DS22q11.2 are directly influenced by all
irrelevant stimuli in the immediate vicinity of the target,
providing further evidence for the inability to dynamically alter their attentional focus.
Finally, and perhaps most importantly, evaluation of
the Gratton effect indicates that children with DS22q11.2
appear to have particular difficulties in the dynamic
monitoring of conflict in their environment. Their
performance suggests that children with DS22q11.2
are unable to use the ongoing context of conflicting
information to modify their attentional focus. This was
apparent in the case of repeated incongruent flanker trials.
Control children were able to benefit from the identical
attentional demands of the adjacent trials, while the
reoccurrence of the incongruent flankers had the reverse
effect of increasing the inhibitory load for children with
DS22q11.2. This deficit may be a result of difficulties
with stimulus–response conflict monitoring which is a
function of the anterior cingulate (Botvinick et al., 1999).
It may also be a result of difficulties with adapting to the
existing conflict through inhibitory processes, which is a
function of the dorsolateral prefrontal cortex. Finally,
© Blackwell Publishing Ltd. 2005
41
the problem could result from an interaction between
the frontal executive network and the ability to dynamically shift the focus of attention in space, which results
from posterior parietal functioning (Casey et al., 2000).
Hypothetically, the conflict monitoring and inhibition
process of the frontal executive network may be intact,
but the mechanism to shift attention away from irrelevant stimuli may be dysfunctional.
Interestingly, the results of this study did not replicate
our previous findings of a relative inefficiency for target
processing in invalidly cued locations compared to validly cued locations (Simon et al., 2005). One possible
explanation of this failure to replicate the previous finding is the nature of the spatial cue. Our previous data
used an endogenous, centrally located cue that requires
that the individual participant interpret the symbolic
meaning of the cue. This entails top-down evaluation
prior to shifting the attentional focus. The current experiment used an exogenous cue, presented at the actual
location of the target. Such cues automatically elicit the
focus of attention to the cued location without the need
for top-down interpretive processing (e.g. McCormick,
1997). This difference, along with the current demonstration of dysfunction of the executive network, may
also indicate that children with DS22q11.2 have specific
difficulties with the interaction of the top-down attentional networks with visuo-spatial processing, that is,
orienting and executive control.
Given the growing knowledge of the relationships
between genetic disorders, executive dysfunction and the
development of psychopathology, this investigation of
the attentional networks in children with DS22q11.2 has
potentially important clinical applications. As already
mentioned, there is a strong link between DS22q11.2 and
the development of psychopathology, especially schizophrenia. Individuals with schizophrenia commonly
demonstrate executive control dysfunction of the sort
reported here. Additionally, there is a strong relationship
between executive dysfunction and COMT genotype in
DS22q11.2. This study provides direct evidence of executive control dysfunction in children with DS22q11.2. In
doing so, it notably replicates and extends earlier results
(e.g. Sobin et al., 2004), but it may also indicate that
executive control (i.e. functioning of the anterior executive control network), or the interaction between executive
control and the spatial attention system (i.e. functioning
of the posterior attention network) might act as potential
biomarkers for the development of psychopathology in
this group. For example, early risk factors for the development of psychopathology in this group may include the
executive dysfunction demonstrated here.
Based on the limited cross-sectional nature of this study,
it is impossible to determine whether the demonstrated
42
Joel P. Bish et al.
executive dysfunction continues into adulthood and
contributes to psychopathology, or simply that children
with DS22q11.2 exhibit a slower trajectory towards
normally developed executive control. Indeed, in typically developing children it appears that prefrontal
activation in response to cognitive control continues to
develop into adolescence (Bunge, Dudukovic, Thomason, Vaidya & Gabrieli, 2002). However, our ongoing
studies are attempting to address that issue. Finally,
further studies, perhaps using functional neuroimaging,
are necessary to determine which specific interpretation
mentioned above is more accurate. Specifically, future
investigations should be able to clarify whether the dysfunction demonstrated by children with DS22q11.2 is
caused by disruption of the frontal, executive system, the
parietal orienting system, or a combination of the two.
It is clear that investigations of specific cognitive functions, like those shown here and in Sobin et al. (2004),
will help to develop a characterization of the intricate
deficits demonstrated in this population and facilitate
progress towards the development of early screening and
intervention techniques designed to improve long-term
outcomes.
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Received: 1 April 2004
Accepted: 3 August 2004