Psychological Medicine (2014), 44, 2661–2671.

© Cambridge University Press 2014 OR I G I N A L A R T I C L E

doi:10.1017/S0033291714000038

Neural correlates of inhibitory control and visual

processing in youths with attention deficit
hyperactivity disorder: a counting Stroop functional
MRI study

L.-Y. Fan1, S. S.-F. Gau1,2,3,4* and T.-L. Chou1,3,4*

1
Department of Psychology, National Taiwan University, Taipei, Taiwan
2
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
3
Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan
4
Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei, Taiwan

Background. Despite evidence of inhibitory control and visual processing impairment in attention deficit hyperactivity
disorder (ADHD), knowledge about its corresponding alterations in the brain is still evolving. The current study used
counting Stroop functional MRI and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investi-
gate if brain activation of inhibitory control and visual processing would differ in youths with ADHD relative to neuro-
typical youths.

Method. We assessed 25 youths with ADHD [mean age 10.9 (S.D. = 2.2) years] and 23 age-, gender- and IQ-matched
neurotypical youths [mean age 11.2 (S.D. = 2.9) years]. The participants were assessed by using the Wechsler
Intelligence Scale for Children, third edition, and two tests from the CANTAB: rapid visual information processing
(RVP) and pattern recognition memory (PRM) outside the scanner.

Results. Youths with ADHD showed more activation than neurotypical youths in the right inferior frontal gyrus
[Brodmann area (BA) 45] and anterior cingulate cortex, which were correlated with poorer performance on the RVP
test in the CANTAB. In contrast, youths with ADHD showed less activation than neurotypical youths in the left superior
parietal lobule (BA 5/7), which was correlated with the percentage of correct responses on the PRM test in the CANTAB.

Conclusions. Our findings suggest that youths with ADHD might need more inhibitory control to suppress interference
between number and meaning and may involve less visual processing to process the numbers in the counting Stroop task
than neurotypical youths.

Received 29 May 2013; Revised 6 December 2013; Accepted 18 December 2013; First published online 22 January 2014

Key words: Cambridge Neuropsychological Test Automated Battery (CANTAB), counting Stroop functional MRI,
inhibitory control, visual processing.

Introduction with greater reductions in visual processing than in

verbal processing are noted in ADHD (Rhodes et al.
Attention deficit hyperactivity disorder (ADHD) is a
2005). In the present study, we used functional mag-
common, early-onset, clinically and genetically hetero-
netic resonance imaging (fMRI) to explore the neural
geneous neuropsychiatric disorder. Individuals with
correlates of these two processes (i.e. inhibitory control
ADHD may have life-long deficits in executive func-
and visual processing), which allowed us to examine
tions (Gau et al. 2010a) and visual memory (Shang &
putative compensatory mechanisms in ADHD. It is im-
Gau, 2011). Among executive function deficits,
portant to examine these two processes within a study
impaired inhibitory control is the most prominent cog-
to understand deficits in the fronto-parietal network
nitive deficit in ADHD (Barkley & Routh, 1974; as
(Fassbender & Schweitzer, 2006; Nakao et al. 2011;
reviewed in Durston, 2003). Moreover, impairments
Cortese et al. 2012).
Evidence of disturbed structural and functional con-
nectivity in fronto-parietal networks in ADHD was
* Address for correspondence: T.-L. Chou, Ph.D., Department of
further provided by a recent meta-analysis of task-
Psychology, National Taiwan University, No. 1, Sec. 4, Roosevelt
Road, Taipei, 106, Taiwan.
based fMRI studies (Cortese et al. 2012) and structural
(Email: tlchou25@ntu.edu.tw) [T.-L. Chou] MRI studies (Nakao et al. 2011). Cortese et al.
(Email: gaushufe@ntu.edu.tw) [S. S.-F. Gau] (2012) reported that hypoactivation in fronto-parietal
2662 L.-Y. Fan et al.
networks is the most frequently observed functional
imaging finding in children with ADHD; Nakao et al.
(2011) reported abnormal gray matter volumes in pre-
frontal, anterior cingulate cortex (ACC), and parietal
regions in children with ADHD. According to a
meta-analysis of patients with ADHD (Hart et al.
2013), most imaging studies have shown abnormal
neural activity for inhibitory control in the right in-
ferior frontal gyrus (IFG), ACC, and parietal regions.
First, impaired IFG functions reduced the ability to
optimally recruit subsidiary brain regions and strate-
gies to perform cognitive tasks in ADHD (Fassbender
& Schweitzer, 2006). The IFG has been implicated in
higher-level cognitive functioning, including atten-
tional processes, inhibitory control, working memory
and planning (Fassbender & Schweitzer, 2006; Bush,
2011). Particularly, the right IFG is thought to be
involved in response inhibitory control or target detec-
tion (Durston, 2003; Hampshire et al. 2010; Cortese
et al. 2012). Second, the ACC is also believed to play
critical roles in complex and effortful cognitive proces-
sing, target detection, response selection and inhibitory
control, error detection, performance monitoring, and
motivation (as reviewed in Bush, 2011). A number of
studies have implicated that the ACC is involved in
top-down attentional control and inhibitory control
of competing responses to various stimuli (Pardo
et al. 1990). Studies have shown hypoactivity in the
ACC and robust activity in the right IFG in adults
with ADHD using the counting Stroop task (Bush
et al. 1999). Third, parietal activations have been
reported to be involved in attention and visual proces-
sing (Fassbender & Schweitzer, 2006; Schneider et al.
2010). Specifically, the superior parietal lobule (SPL)
in the left hemisphere has been suggested to be asso-
ciated with number processing on screen in healthy
adults (Dehaene et al. 2003; Cavanna & Trimble,
2006). Bush et al. (1998) and Lévesque et al. (2006)
found robust activity in the left SPL/precuneus
[Brodmann area (BA) 7] during a counting Stroop task.
Neuropsychological studies have combined several
constructs, namely executive functions and visual pro-
cessing, into a single study to examine drug-related im-
provement among children with ADHD (Coghill et al.
2007, Shang & Gau, 2012). Previous imaging studies
have also combined inhibitory control and sustained
attention into a single task using the Go/No-Go task
in ADHD (Trommer et al. 1988; Schulz et al. 2004;
Fassbender & Schweitzer, 2006). They found that com-
mission errors (failure to inhibit to the no-go response)
were related to inhibitory control and impulsivity, and
omission errors (failure to respond to the go stimulus)
were associated with inattention. The counting Stroop
task is designed to evaluate the underlying mechan-
ism of cognitive interference between number and
meaning (Bush et al. 1998), and the visual properties
of the numbers to evaluate visual processing
(Rasmussen & Bisanz, 2005). In the current study, we
used the counting Stroop task to explore the differen-
tial brain activity related to visual processing load be-
tween the ADHD and neurotypical groups, in
addition to inhibitory control that has been explored
in fMRI studies.
The Cambridge Neuropsychological Test Auto-
mated Battery (CANTAB) was also used to examine
these two processes. The CANTAB has been used to
assess executive functions, including both inhibitory
control and visual processing. Previous studies have
shown that children with ADHD perform worse in re-
sponse inhibitory control (Slaats-Willemse et al. 2007;
Gau et al. 2009; Gau & Shang, 2010a, b; Gau &
Huang, 2014) and visual memory (Rhodes et al. 2005;
Gau et al. 2009; Gau & Shang, 2010a; Shang & Gau,
2011), as compared with neurotypical children. Pre-
vious studies have also suggested that the deficits in
inhibitory control and visual processing are major
endophenotypes for ADHD genetic studies (Gau &
Shang, 2010a; Shang & Gau, 2011). Hence, combining
the CANTAB and counting Stroop fMRI offers a better
understanding of the relationships among these two
processes. We used the CANTAB to assess partici-
pants’ cognitive mechanisms of inhibitory control
and visual processing load outside the scanner because
the CANTAB has been reported to be used to measure
the endophenotypes for ADHD (Doyle et al. 2005;
Gau & Shang, 2010a; Shang & Gau, 2011; Gau &
Huang, 2014). In addition, previous studies have
shown that the deficits in inhibitory control and visual
processing are major endophenotypes for ADHD gen-
etic studies (Gau & Shang, 2010a; Shang & Gau, 2011).
Despite the striking nature of the inhibitory control
and visual processing impairment in ADHD, knowl-
edge about its corresponding alterations in the brain
is still evolving. Previous studies have used the ap-
proach of correlating the structural integrity of fiber
tracts based on a group difference with the CANTAB
to investigate executive function and inhibitory
control in children with ADHD (Shang et al. 2012;
Wu et al. 2014). In the findings of Konrad et al.
(2012), adults with ADHD had significantly lower
structural integrity in the left inferior longitudinal
fasciculus based on a group difference, which was
negatively correlated with attentional performance of
the test of variables of attention. Therefore, the present
study was designed to use the approach of correlating
brain activity and the CANTAB to assess the differen-
tial inhibitory control and visual processing between
the ADHD and neurotypical groups. Two tests of in-
hibitory control and visual processing were chosen
from the CANTAB.

Studies on brain activity in the right IFG and
parietal regions have revealed inconsistent results in
terms of increased or decreased activation in ADHD
(Fassbender & Schweitzer, 2006; Silk et al. 2008;
Bush, 2011; Hart et al. 2013). These studies are
mainly limited by separate investigations of these
two brain regions and the study of adult populations.
We therefore used counting Stroop fMRI to examine
the neural correlates of inhibitory control and visual
processing, and correlated the brain activity with the
CANTAB in youths with ADHD and neurotypical
youths. According to a priori hypotheses, we hypo-
thesized that the involvement of the right IFG and
ACC may be related to the inhibitory control that
can be measured by the CANTAB in youths with
ADHD, and that the involvement of the parietal
regions may be related to the visual processing that
can be measured by the CANTAB in neurotypical
youths.
Method
Participants and procedures
We assessed 25 youths (mean age = 10.9 years,
S.D. = 2.2 years, age range 8–16 years, two females)
with a clinical diagnosis of ADHD according to the
Diagnostic and Statistical Manual of Mental Dis-
orders, fourth edition (DSM-IV) diagnostic criteria
and 23 neurotypical youths without ADHD (mean
age = 11.2 years, S.D. = 2.9 years, age range 8–16 years,
two females) who were matched to the distribution
of age, gender, handedness and intelligence quotient
(IQ) of the ADHD group. Youths with ADHD
were recruited from the Department of Psychiatry
(National Taiwan University Hospital, Taipei, Tai-
wan). The participants and their parents were inter-
viewed to confirm their diagnosis of ADHD and to
exclude any other psychiatric disorders by one of
the corresponding authors (S. S.-F. Gau) using the
Chinese Kiddie epidemiological version of the
Schedule for Affective Disorders and Schizophrenia
(K-SADS-E) interview (Gau et al.2005). The neurotypi-
cal group was recruited from similar school districts as
the ADHD group with the help of principals and
schoolteachers rather than by advertisement outside
schools. Similar to the ADHD group, they and
their parents were interviewed using the Chinese
K-SADS-E to ensure that they did not meet DSM-IV di-
agnosis of ADHD from early childhood until now and
any of the other psychiatric disorders.
Both groups were native Mandarin–Chinese
speakers, had standard scores of the full-scale IQ
greater than 80 as assessed by the Wechsler Intelli-
gence Scale for Children, third edition (WISC-III;
Inhibitory control and visual processing in ADHD 2663
Wechsler, 1991), and had normal hearing and
normal or corrected-to-normal vision. Participants
who had a clinical diagnosis of any other psychiatric
disorders were excluded from the study. In addition,
participants with ADHD who currently took medi-
cation affecting the central nervous system, and neuro-
typical participants who ever or currently took any
psychotropic drug and had a history of attention or
verbal-language deficits were excluded from the
study.
The study was approved by the Research Ethics
Committee at the National Taiwan University
Hospital, Taiwan and all the participants and their
parents provided written informed consent before
study implementation (IRB no. 200903062R;
ClinicalTrials.gov no. NCT00916851). All the partici-
pants were assessed using the Chinese K-SADS-E
interviews, followed by the WISC-III and the
CANTAB. The six participants with ADHD,
who took psychotropic medication before, did not
take any medication for at least 1 week before the
assessments.
Functional activation task
In the counting Stroop task, experimental stimuli were
divided into congruent, incongruent and control con-
ditions (see Fig. 1), with 24 trials in each condition.
In the ‘congruent’ condition, the number of words
was consistent with the meaning of the word such as
‘one’, ‘two’, ‘three’ or ‘four’ (i.e. , , or in
Chinese). In the ‘incongruent’ condition, the number
of words was inconsistent with the meaning of the
word. In the ‘control’ condition, the Chinese words
did not give any clue to number [i.e. (it; pronoun),
(human; noun), (understand; verb) or (no; ad-
verb)]. All the words of the three conditions were
matched for the number of syllables, visual complexity
(strokes per word) and frequency.
Trials consisted of a solid square (500 ms), followed
by sets of between one and four identical words
(3200 ms). There was a 200-ms blank between trials.
Participants were instructed to report the number of
words in each set via button-press with one, two,
three and four buttons from left to right on the keypad.
They used their index and middle fingers of each hand
to respond accordingly.
WISC-III
The WISC-III (Wechsler, 1991) has been widely used
to assess full-scale intelligence levels of children aged
6 years to 16 years, 11 months. Among the 13 subtests,
forward and backward digit spans were used to
2664 L.-Y. Fan et al.
Fig. 1. The counting Stroop task in Chinese. Experimental stimuli were divided into congruent, incongruent and control
conditions. In the ‘congruent’ condition, the number of words (i.e. one) was consistent with the meaning of the word (i.e.
one). In the ‘incongruent’ condition, the number of words (i.e. three) was inconsistent with the meaning of the word (i.e.
four). In the ‘control’ condition, the Chinese words did not give any clue to number.
represent the index of sustained attention and verbal
working memory, respectively.
Neuropsychological measures
The CANTAB is a standard, computerized, non-
linguistic and culturally blind test to assess a wide
range of executive functions and visual processing.
Rapid visual information processing (RVP) was chosen
to assess inhibitory control (Sahakian et al. 1989; Gau &
Huang, 2014), while pattern recognition memory
(PRM) was used to assess visual processing (Shang &
Gau, 2011, 2012).
In the RVP test, participants were asked to respond
to the specific sequence of digits, when a white box
was presented in the center of the screen with digits
(ranging from 2 to 9) appearing one at a time
(100 digits/min) in the center of the screen in a
pseudo-random order. Participants were instructed to
respond to three specific number sequences of digits
(i.e. 2–4–6, 3–5–7, 4–6–8) by pressing the touch pad.
Two measures were recorded: A’, a signal detection
measure of sensitivity to the target, regardless of
response tendency (Sahgal, 1987); and probability of
false alarms (of the participant responding inappropri-
ately), i.e. total false alarms divided by the sum of total
false alarms and total correct rejections.
The PRM test is designed to measure the capacity of
visual processing in a two-choice forced discrimination
paradigm (Sahakian et al. 1988). Participants were pre-
sented with a series of visual geometric patterns, one
at a time, in the center of the screen. In the recognition
phase, participants were presented with two geometric
patterns and the test patterns were presented in the
reverse order to the original order of presentation.
The participants were instructed to choose the correct
pattern between an already-seen pattern and a novel
pattern. The percentage of correct responses was
recorded.
MRI image acquisition
Participants lay in the scanner with their head position
secured. The head coil was positioned over the partici-
pants’ head. Participants viewed visual stimuli pro-
jected onto a screen via a mirror attached to the
inside of the head coil. Each participant performed
two functional runs. Each run took 2.8 min. Images
were acquired using a 3-T Siemens Tim-Trio scanner
with the 32-channel head coil (Siemens Medical
Solutions, Germany). Each functional run had 85
image volumes that were acquired with the echo
planar imaging method to detect the blood oxygen-
ation level-dependent (BOLD) signal.
The scanning parameters were the following: rep-
etition time (TR) = 2000 ms; echo time (TE) = 24 ms;
flip angle = 90°; matrix size = 64 × 64; field of view =
25.6 cm; slice thickness = 3 mm; number of slices = 34.
A high-resolution, T1-weighted three-dimensional
image was also acquired (magnetization prepared
rapid gradient-echo; TR = 2300 ms; TE = 2.98 ms;
flip angle = 9°; matrix size = 256 × 256; field of view =
25.6 cm; slice thickness = 1 mm). The orientation of
the three-dimensional image was identical to the func-
tional slices. The task was administered in a pseudo-
random order for all participants for event-related
design (Burock et al. 1998). We used the Optseq script
for randomized event-related design (http://surfer.
nmr.mgh.harvard.edu/optseq, written by D. Greve,
Charlestown, MA, USA) that implemented the
Burock et al. (1998) approach.
Image and statistical analysis
Data analysis was performed using SPM5 (Statistical
Parametric Mapping). The functional images were cor-
rected for the differences in slice-acquisition time to the
middle volume and were realigned to the first volume
in the scanning session using affine transformations.
 Inhibitory control and visual processing in ADHD 2665

The exclusion criteria for motion were 3 mm for dis- PRM tests. All reported results were significant using
placement and 3° for rotations. No participant had p < 0.05.
more than 3 mm of movement in any plane. Co-
registered images were normalized to the Montreal
Results
Neurological Institute (MNI) average template.
Statistical analyses were calculated on the smoothed Behavioral results
data (10 mm isotropic Gaussian kernel, the concept of
There were no group differences in IQ profiles, or digit
kernel was defined the shape of function to calculate
span forward. Compared with neurotypical youths,
weighted average of each data point with its neighbor-
youths with ADHD had significantly fewer digits
ing data points), with a high-pass filter (128 s cut-off
recalled backward, and lower scores on A’ (target sen-
period) in order to remove low frequency artifacts.
sitivity), higher probability of false alarm in the RVP
Data from each participant were entered into a
test, and lower percentage of correct responses in the
general linear model using an event-related analysis
PRM test (Table 1).
procedure (Josephs & Henson, 1999). Stimuli were
Online Supplementary Table S1 presents the accu-
treated as individual events for analysis and modeled
racy and reaction time of the counting Stroop test in
using a canonical hemodynamic response function
the three conditions by the two groups. A two-way
(HRF). Parameter estimates from contrasts of the ca-
ANOVA on accuracy revealed significant main effects
nonical HRF in single-subject models were entered
of condition (F2,92 = 14.58, p < 0.01), with being more
into random-effects analysis using the one-sample
accurate in the congruent and control conditions than
t test across all participants to determine whether acti-
the incongruent condition (t47 = 4.91, p < 0.01; t47 = 3.77,
vation during a contrast was significant (i.e. parameter
p < 0.01, respectively), but no significant effect of
estimates were reliably greater than 0) in a whole
group (F1,46 = 1.59, p = 0.214). The interaction of group
brain analysis. There were three event types: congru-
and condition was not significant (F2,92 = 0.37, p = 0.692).
ent, incongruent, and control. To observe the neural
Regarding reaction time, a two-way ANOVA
correlates of inhibitory control, we compared the in-
showed a significant main effect of condition (F2,92 =
congruent with the congruent condition. To further
20.37, p < 0.01), with shorter reaction time in the
observe the neural correlates of visual processing, we
congruent and control conditions than in the incongru-
compared the larger number of words (i.e. ‘three’
ent condition (t47 = −5.33, p < 0.01; t47 = −5.40, p < 0.01,
and ‘four’) with the fewer number of words (i.e. ‘one’
respectively) but a marginally significant effect of
and ‘two’) in the incongruent condition and in the
group (F1,46 = 4.00, p = 0.052). The interaction of group
congruent condition. For the contrast within each
and condition was not significant (F2,92 = 2.85, p = 0.063).
group, all reported areas of activation were significant
To further observe visual processing in the congru-
using p < 0.05 for family-wise error (FWE) corrected at
ent and incongruent conditions, the larger number of
the voxel level with a cluster size greater than 50 voxels
words (i.e. ‘three’ and ‘four’) showed significant longer
in a whole brain analysis. For the contrasts between
reaction time than the fewer number of words (i.e.
groups, all reported areas of activation were significant
‘one’ and ‘two’) (t95 = −2.13, p < 0.05), suggesting that
using p < 0.05 for FWE corrected at the voxel level with
all participants spent more time in making judgments
a cluster size greater than 10 voxels, with the anatom-
as the number of words increased.
ical masks of right IFG, ACC, and left SPL due to our
a priori hypothesis. The three anatomical masks
fMRI results
were defined from the WFU PickAtlas, with the option
of right IFG, ACC, and left SPL (http://fmri.wfubmc. Table 2 presents activation of brain regions for the in-
edu/software/PickAtlas). We then extracted the β congruent versus congruent condition for the ADHD
values from peak voxels of significant brain regions be- and neurotypical groups. For the contrast of ‘incongru-
tween groups. ent versus congruent condition’ within group, the
We used SPSS to conduct statistical analysis ADHD group showed greater activation in the right
(IBM, USA). The descriptive results were displayed IFG (BA 45) and ACC (online Supplementary Fig. S1,
as frequency and percentage for categorical variables, Table 2). For group comparisons, youths with ADHD
and mean and S.D. for continuous variables. We also had greater activation in the right IFG (BA 45) and
conducted two-way analysis of variance (ANOVA) ACC than neurotypical youths (Fig. 2, Table 2). There
with group and condition interactions for behavioral was no significant activation for neurotypical youths
results of the counting Stroop test. Moreover, we per- as compared with youths with ADHD.
formed Pearson’s correlations between β values of For the contrast of ‘larger versus fewer numbers of
peak voxels of significant brain regions and the words’ within group, the ADHD group showed
scores of the parameters derived from the RVP and greater activation in the left postcentral gyrus (BA 3),
2666 L.-Y. Fan et al.

Table 1. Age, IQ scores, and performance in the RVP and PRM tests for all participants

ADHD (n = 25) Neurotypical (n = 23) p

Gender, n
Male 23 21
Female 2 2
Age, years 10.9 (2.2) 11.2 (2.9) 0.667
Range 8–16 8–16
WISC-III
Verbal IQ 109.8 (10.1) 111.1 (7.9) 0.628
Performance IQ 104.0 (11.1) 105.2 (9.5) 0.676
Full-scale IQ 107.2 (10.8) 109.1 (7.5) 0.496
Digit span
Forward 8.0 (1.2) 8.3 (0.7) 0.177
Backward 4.8 (1.8) 5.9 (1.8) 0.034
RVP
A’ 0.83 (0.06) 0.87 (0.08) 0.018
Probability of false alarm 0.025 (0.031) 0.010 (0.010) 0.044
PRM
Percentage of correct responses 90.2 (4.1) 93.0 (4.4) 0.049

IQ, Intelligence quotient; RVP, rapid visual information processing; PRM, pattern recognition memory; ADHD, attention
deficit hyperactivity disorder; WISC-III, Wechsler Intelligence Scale for Children, Third Edition; A’, signal detection measure
of sensitivity to the target.
Data are given as mean (standard deviation).

Table 2. Inhibitory control: greater activation for the incongruent compared with congruent condition within each group, and between the two
groupsa

MNI coordinatesb

Cortical regions H BA Voxelsc Z test x y z

Incongruent versus congruent condition

ADHD group
Inferior frontal gyrus R 45 86 4.96 30 15 12
Anterior cingulate cortex* L 24/32 15 3.52 −3 30 0
R 24/32 15 3.44 3 30 0
Neurotypical group
Inferior frontal gyrus† R 11/47 6 1.81 24 45 −12
Neurotypical > ADHD group
None
ADHD > Neurotypical group
Inferior frontal gyrus* R 45 22 4.49 33 18 12
Anterior cingulate cortex* L 32 343 3.77 −9 21 24
R 32 – 3.57 12 30 18

MNI, Montreal Neurological Institute; H, hemisphere; BA, Brodmann area; ADHD, attention deficit hyperactivity disorder;
R, right; L, left; FWE, family-wise error.
a
Region of interest masks (anatomical masks of right inferior frontal gyrus, anterior cingulate cortex, and left superior
parietal lobule) were only used in between-group analysis.
b
Coordinates of activation peak(s) within a region based on a Z test are given in the MNI stereotactic space (x, y, z).
c
Number of voxels in cluster at p < 0.05 FWE corrected, only clusters greater than or equal to 50 are presented.
* p < 0.05 for FWE corrected with the use of an anatomical mask.
† p < 0.05 for uncorrected.
 Inhibitory control and visual processing in ADHD 2667

Fig. 2. (a) Inhibitory control. Greater activation was found in the right inferior frontal gyrus [IFG; Brodmann area (BA) 45]
and anterior cingulate cortex (ACC) with region of interest (ROI)-masked analysis for the attention deficit hyperactivity
disorder (ADHD) group as compared with the neurotypical group during the contrast of ‘incongruent versus congruent
condition’. (b) Visual processing. Greater activation was found in the left superior parietal lobule (SPL; BA 5/7) with
ROI-masked analysis for the neurotypical group as compared with the ADHD group during the contrast of ‘larger versus
fewer numbers of words’. The color bar presents the strength of the activation.

while the neurotypical group showed greater acti- Discussion

vation in the left precentral gyrus (BA 6) and left SPL
(BA 5/7) (online Supplementary Fig. S2, Table 3). For
group comparisons, neurotypical youths had greater
activation in the left SPL as compared with youths
with ADHD (Table 3).
Correlations between brain activation and
neuropsychological measures
Pearson correlations showed that in the ADHD group,
increasing activation in the right IFG (for inhibitory
control) was positively correlated with probability of
false alarm in the RVP test (r = 0.52, p < 0.05), and in-
creasing activation in the right ACC (for inhibitory
control) was positively correlated with probability of
false alarm in the RVP test (r = 0.51, p < 0.05) (removing
an outlier with outside 2.5 s.D. from the group mean).
In the neurotypical group, increasing activation in the
left SPL (for visual processing) was positively corre-
lated with the percentage of correct responses in the
PRM test (r = 0.52, p < 0.05), suggesting that neuro-
typical youths might have better visual processing
than youths with ADHD.
Several features of this study constitute its strengths:
combination of neuropsychological and functional
neuroimaging assessments to investigate inhibitory
control and visual processing in ADHD; neuropsycho-
logical assessments of the two processes as proposed
potential ADHD cognitive endophenotypes using the
CANTAB; and assessment of neural mechanisms of
two functions using counting Stroop fMRI. The major
findings were that youths with ADHD showed greater
activation in the right IFG and ACC during the incon-
gruent versus congruent condition but less activation in
the left SPL for the larger versus fewer numbers of
words than neurotypical youths. Moreover, positive
correlations of activation of the right IFG and ACC
with probability of false alarm in the RVP test were
only noted in youths with ADHD; however, a positive
correlation of activation of the left SPL with the per-
centage of correct responses in the PRM test was
only noted in neurotypical youths.
Our finding of more brain activation in the right IFG
and ACC among youths with ADHD than neurotypi-
cal youths was consistent with the findings related to
2668 L.-Y. Fan et al.

Table 3. Visual processing: greater activation for the larger number of words compared with the fewer number of words within each group,
and between the two groupsa

MNI coordinatesb

Cortical regions H BA Voxelsc Z test x y z

Larger versus fewer numbers of words

ADHD group
Postcentral gyrus L 3 58 4.28 −42 −33 66
Superior parietal lobule† L 7 2 1.90 −24 −63 63
Neurotypical group
Precentral gyrus L 6 333 5.45 −33 −15 66
Superior parietal lobuled L 5/7 – 4.64 −45 −42 63
Neurotypical > ADHD group
Superior parietal lobule* L 5/7 47 3.17 −21 −42 63
ADHD > Neurotypical group
None

MNI, Montreal Neurological Institute; H, hemisphere; BA, Brodmann area; ADHD, attention deficit hyperactivity disorder;
L, left; FWE, family-wise error.
a
Region of interest masks (anatomical masks of right inferior frontal gyrus, anterior cingulate cortex, and left superior
parietal lobule) were only used in between group analysis.
b
Coordinates of activation peak(s) within a region based on a Z test are given in the MNI stereotactic space (x, y, z).
c
Number of voxels in cluster at p < 0.05 FWE corrected, only clusters greater than or equal to 50 are presented.
d
Subcluster.
* p < 0.05 for FWE corrected with the use of an anatomical mask.
† p < 0.05 for uncorrected.

inhibitory control (Fassbender & Schweitzer, 2006;
Bush, 2011). Previous fMRI studies have suggested
that children and adults with ADHD might engage
in alternative, compensatory brain regions with con-
comitant cognitive strategies due to a selectively weak-
ened neural system (for a review, see Fassbender &
Schweitzer, 2006). They suggested that hyperactivity
in a brain region can be considered as ‘inefficiency’ be-
cause an individual needs to use more energy than
should be to perform a given task. Moreover, extra ac-
tivity in the clinical group may be viewed as com-
pensatory activity of brain regions that the clinical
group is enrolling in order to compensate for under-
activity in the ‘appropriate’ brain network
(Fassbender & Schweitzer, 2006). With regards to
ADHD studies, Schulz et al. (2004) have suggested
the recruitment of additionally compensatory pre-
frontal regions to perform the Go/No-Go task in
ADHD. Moreover, an earlier study showed that indivi-
duals with ADHD might have an immature prefrontal
cortex, so they may compensate with the recruitment
of additional cortical areas in order to perform at the
same level as that of neurotypical subjects (Rubia
et al.1999). In our findings, greater activations in the
right IFG and ACC among youths with ADHD than
neurotypical youths were consistent with previous
findings related to the inhibitory control process
(Hampshire et al. 2010; Whelan et al. 2012), suggesting
that youths with ADHD might need more activation in
the right IFG and ACC to compensate their deficits
in inhibitory control. According to the meta-analysis
in ADHD (Hart et al. 2013), adult patients with
ADHD relative to controls showed decreased acti-
vation in the right frontal region for inhibitory control.
However, we found that youth participants with
ADHD showed greater activations than neurotypical
youths in the right IFG and ACC. The current study
has added value to the effect of age.
In contrast, youths with ADHD showed less acti-
vation in the left SPL than neurotypical youths.
Previous studies point out that ADHD is associated
with impaired visual processing (Shang & Gau, 2011,
2012) and less activation in the left parietal region
may be attributed to impaired visual processing in
children with ADHD (Silk et al. 2008). Our finding of
a positive correlation between left SPL activation and
the percentage of correct responses in the PRM test
in neurotypical youths suggests that neurotypical
youths might have better visual processing than
youths with ADHD. Taken together, our findings
lend important evidence to support that youths with
ADHD might have worse visual processing of num-
bers as compared with neurotypical youths while per-
forming the counting Stroop task.

Although previous studies have suggested that the
counting Stroop task was designed to evaluate the
neural correlates of inhibitory control (Bush et al.
1998, 1999; Lévesque et al. 2006), visual processing
could also be involved in this task. For example,
Bush et al. (1998) and Lévesque et al. (2006) found ro-
bust activity in the left SPL/precuneus (BA 7) during
a counting Stroop task. In the present study, we used
the contrast of the larger versus the fewer numbers of
words to examine whether visual processing was
involved in the counting Stroop task. Longer reaction
time and greater left SPL activation were related to
visual processing for the larger number of words
compared with the fewer number of words across
participants. Taken together, our findings lend evi-
dence to support that left SPL is related to visual
processing.
More importantly, our further examination of
the relationship between frontal and parietal
functions showed that hyperactivation in the right
IFG was correlated with hypoactivation in the left
SPL (r = −0.29, p < 0.05) across all the participants,
given that the correlations did not vary between
groups (Fisher exact test, z = 0.17, p > 0.05). Our findings
suggest that less activation of parietal regions may
be compensated by increased brain activation in
the right IFG and ACC. As compared with neuro-
typical youths, youths with ADHD might have poor
visual processing associated with parietal regions
that may be related to compensatory inhibitory
control associated with the right IFG. These findings
suggest a deficit on association between frontal and
parietal function in youths with ADHD. In addition
to the significant correlation between frontal and
parietal activations (r = −0.29, p < 0.05), we presented a
significant correlation between congruency cost (incon-
gruent v. congruent) and visual processing (larger
v. fewer words) across all the participants (r = −0.29,
p < 0.05) on reaction time after partialing for medication
status.
Limitations
Relatively small sample size and potential effect of
methylphenidate on six participants are the two
methodological limitations of this study. Although
our results were consistent and statistically reliable,
the sample size was small (statistical power 0.544,
effect size 0.611). Therefore, the findings should be
interpreted with caution until replicated in a larger
sample size. Moreover, six of the participants with
ADHD had ever been treated with methylphenidate
some time at least 1 week before MRI assessment; the
effect of methylphenidate on cognitive performance
cannot be excluded.
Inhibitory control and visual processing in ADHD 2669
Implications
Our results clearly contribute to our knowledge about
cognitive deficits in ADHD, which are not only dem-
onstrated by deficits in inhibition controls and visual
processing assessed by neuropsychological tests but
also by functional imaging research. Most importantly,
our findings of compensatory neuronal mechanisms
revealed by imaging data are not clinically observable;
hence, imaging assessment may be recommended to be
included in the assessment of ADHD, particularly for
the diagnosis of complicated cases.
Conclusion
As the first study combining the CANTAB and the
counting Stroop task during fMRI scanning to examine
inhibitory control and visual processing in ADHD, the
findings of greater activation in the right IFG and ACC
in ADHD imply increased inhibitory control to sup-
press interference between number and meaning in
ADHD. In contrast, the finding of less activation in
the left SPL in ADHD suggests a deficit in visual pro-
cessing to process the numbers in the counting Stroop
task in ADHD. Taken together, in view of that the
fronto-parietal network is considered to be impaired
in ADHD (Makris et al. 2008), our findings add some
evidence to suggest that less activation of parietal
regions may be compensated by increased brain acti-
vation in the right IFG.
Supplementary material
For supplementary material accompanying this paper
visit http://dx.doi.org/10.1017/S0033291714000038.
Acknowledgements
This work was supported by the National Science
Council of Taiwan (NSC) (NSC98-3112-B-002-004,
NSC99-2627-B-002-016 and NSC100-2627-B-002-013
to T.-L.C.; NSC96-2628-B-002-069-MY3, NSC99-2627-
B-002-015, NSC100-2627-B-002-014 and NSC101-
2627-B-002-002 to S.S.-F.G.) and the National Health
Research Institute (NHRI) (NHRI-EX98-9407PC and
NHRI-EX100-0008PI to S.S.-F.G.) and in part by the
Department of Medical Imaging and the 3 T MRI
Laboratory in the National Taiwan University Hos-
pital.
Declaration of Interest
None.
2670 L.-Y. Fan et al.
References
Barkley RA, Routh DK (1974). Reduction of children’s
locomotor activity by modeling and the promise of
contingent reward. Journal of Abnormal Child Psychology 2,
117–131.
Burock MA, Buckner RL, Woldorff MG, Rosen BR,
Dale AM (1998). Randomized event-related experimental
designs allow for extremely rapid presentation rates using
functional MRI. Neuroreport 9, 3735–3739.
Bush G (2011). Cingulate, frontal, and parietal cortical
dysfunction in attention-deficit/hyperactivity disorder.
Biological Psychiatry 69, 1160–1167.
Bush G, Frazier JA, Rauch SL, Seidman LJ, Whalen PJ,
Jenike MA, Rosen BR, Biederman J (1999). Anterior
cingulate cortex dysfunction in attention deficit/
hyperactivity disorder revealed by fMRI and the counting
Stroop. Biological Psychiatry 45, 1542–1552.
Bush G, Whalen PJ, Rosen BR, Jenike MA, Mcinerney SC,
Rauch SL (1998). The counting Stroop: an interference
task specialized for functional neuroimaging–validation
study with functional MRI. Human Brain Mapping 6,
270–282.
Cavanna AE, Trimble MR (2006). The precuneus: a review of
its functional anatomy and behavioural correlates. Brain
129, 564–583.
Coghill DR, Rhodes SM, Matthews K (2007). The
neuropsychological effects of chronic methylphenidate on
drug-naive boys with attention-deficit/hyperactivity
disorder. Biological Psychiatry 62, 954–962.
Cortese S, Kelly C, Chabernaud C, Proal E, Martino AD,
Milham MP, Castellanos FX (2012). Toward systems
neuroscience of ADHD: a meta-analysis of 55 fMRI studies.
American Journal of Psychiatry 169, 1038–1055.
Dehaene S, Piazza M, Pinel P, Cohen L (2003). Three parietal
circuits for number processing. Cognitive Neuropsychology
20, 487–506.
Doyle AE, Willcuttc EG, Seidman LJ, Biederman J,
Chouinard VA, Silva J, Faraone SV (2005). Attention-
deficit/hyperactivity disorder endophenotypes. Biological
Psychiatry 57, 1324–1335.
Durston S (2003). A review of the biological bases of ADHD:
what have we learned from imaging studies? Mental
Retardation and Developmental Disabilities Research Reviews 9,
184–195.
Fassbender C, Schweitzer JB (2006). Is there evidence for
neural compensation in attention deficit hyperactivity
disorder? A review of the functional neuroimaging
literature. Clinical Psychology Review 26, 445–465.
Gau SS, Chiu C-D, Shang C-Y, Cheng AT-A, Soong W-T
(2009). Executive function in adolescence among children
with attention-deficit/hyperactivity disorder in Taiwan.
Journal of Developmental and Behavioral Pediatrics 30, 525–534.
Gau SS, Chong MY, Chen THH, Cheng ATA (2005).
A 3-year panel study of mental disorders among
adolescents in Taiwan. American Journal of Psychiatry 162,
1344–1350.
Gau SS, Huang W-L (2014). Rapid visual information
processing as a cognitive endophenotype for attention
deficit hyperactivity disorder. Psychological Medicine 44,
435–446.
Gau SS, Shang C-Y (2010a). Executive functions as
endophenotypes in ADHD: evidence from the Cambridge
Neuropsychological Test Battery (CANTAB). Journal of
Child Psychology and Psychiatry 51, 838–849.
Gau SS, Shang C-Y (2010b). Improvement of executive
functions in boys with attention deficit hyperactivity
disorder: an open-label follow-up study with once-daily
atomoxetine. International Journal of
Neuropsychopharmacology 13, 243–256.
Hampshire A, Chamberlain SR, Monti MM, Duncan J,
Owen AM (2010). The role of the right inferior frontal
gyrus: inhibition and attentional control. Neuroimage 50,
1313–1319.
Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (2013).
Meta-analysis of functional magnetic resonance imaging
studies of inhibition and attention in attention-deficit/
hyperactivity disorder. JAMA Psychiatry 70, 185–198.
Josephs O, Henson RNA (1999). Event-related functional
magnetic resonance imaging: modelling, inference and
optimization. Philosophical Transactions of the Royal Society B:
Biological Sciences 354, 1215–1228.
Konrad A, Dielentheis TF, El Masri D, Dellani PR,
Stoeter P, Vucurevic G, Winterer G (2012). White matter
abnormalities and their impact on attentional performance
in adult attention-deficit/hyperactivity disorder. European
Archives of Psychiatry and Clinical Neuroscience 262, 351–360.
Lévesque J, Beauregard M, Mensour B (2006). Effect of
neurofeedback training on the neural substrates of selective
attention in children with attention-deficit/hyperactivity
disorder: a functional magnetic resonance imaging study.
Neuroscience Letters 394, 216–221.
Makris N, Buka SL, Biederman J, Papadimitriou GM,
Hodge SM, Valera EM, Brown AB, Bush G,
Monuteaux MC, Caviness VS, Kennedy DN, Seidman LJ
(2008). Attention and executive systems abnormalities in
adults with childhood ADHD: a DT-MRI study of
connections. Cerebral Cortex 18, 1210–1220.
Nakao T, Radua J, Rubia K, Mataix-Cols D (2011). Gray
matter volume abnormalities in ADHD: voxel-based
meta-analysis exploring the effects of age and stimulant
medication. American Journal of Psychiatry 168, 1154–1163.
Pardo JV, Pardo PJ, Janer KW, Raichle ME (1990). The
anterior cingulate cortex mediates processing selection in
the Stroop attentional conflict paradigm. Proceedings of the
National Academy of Sciences USA 87, 256–259.
Rasmussen C, Bisanz J (2005). Representation and working
memory in early arithmetic. Journal Experimental Child
Psychology 91, 137–157.
Rhodes SM, Coghill DR, Matthews K (2005).
Neuropsychological functioning in stimulant-naïve boys
with hyperkinetic disorder. Psychological Medicine 35,
1109–1120.
Rubia K, Overmeyer S, Taylor E, Brammer M,
Williams SCR, Simmons A, Bullmore ET (1999).
Hypofrontality in attention deficit hyperactivity disorder
during higher-order motor control: a study with functional
MRI. American Journal of Psychiatry 156, 891–896.

Sahakian BJ, Jones G, Levy R, Gray J, Warburton D (1989).
The effects of nicotine on attention, information processing,
and short-term memory in patients with dementia of the
Alzheimer type. British Journal of Psychiatry 154, 797–800.
Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R,
Philpot M, Robbins TW (1988). A comparative study of
visuospatial memory and learning in Alzheimer-type
dementia and Parkinson’s disease. Brain 111, 695–718.
Sahgal A (1987). Some limitations of indices derived from
signal detection theory: evaluation of an alternative index
for measuring bias in memory tasks. Psychopharmacology 91,
517–520.
Schneider MF, Krick CM, Retz W, Hengesch G,
Retz-Junginger P, Reith W, Rösler M (2010). Impairment
of fronto-striatal and parietal cerebral networks correlates
with attention deficit hyperactivity disorder (ADHD)
psychopathology in adults – a functional magnetic
resonance imaging (fMRI) study. Psychiatry Research:
Neuroimaging 183, 75–84.
Schulz KP, Fan J, Tang CY, Newcorn JH, Buchsbaum MS,
Cheung AM, Halperin JM (2004). Response inhibition in
adolescents diagnosed with attention deficit hyperactivity
disorder during childhood: an event-related fMRI study.
American Journal of Psychiatry 161, 1650–1657.
Shang C-Y, Gau SS (2011). Visual memory as a potential
cognitive endophenotype of attention deficit hyperactivity
disorder. Psychological Medicine 41, 2603–2614.
Shang C-Y, Gau SS (2012). Improving visual memory,
attention, and school function with atomoxetine in boys
with attention-deficit/hyperactivity disorder. Journal of Child
and Adolescent Psychopharmacology 22, 353–363.
Shang CY, Wu YH, Gau SS, Tseng WY (2012). Disturbed
microstructural integrity of the frontostriatal fiber pathways
Inhibitory control and visual processing in ADHD 2671
and executive dysfunction in children with attention
deficit hyperactivity disorder. Psychological Medicine 43,
1093–1107.
Silk TJ, Vance A, Rinehart N, Bradshaw JL, Cunnington R
(2008). Dysfunction in the fronto-parietal network in
attention deficit hyperactivity disorder (ADHD): an fMRI
study. Brain Imaging and Behavior 2, 123–131.
Slaats-Willemse DI, Swaab-Barneveld HJ,
de Sonneville LM, Buitelaar JK (2007). Family-genetic
study of executive functioning in attention-deficit/
hyperactivity disorder: evidence for an endophenotype?
Neuropsychology 21, 751–760.
Trommer BL, Hoeppner JA, Lorber R, Armstrong KJ (1988).
The Go-No-Go paradigm in attention deficit disorder.
Annals of Neurology 24, 610–614.
Wechsler D (1991). Wechsler Intelligence Scale for Children,
3rd edn. The Psychological Corporation: San Antonio, TX.
Whelan R, Conrod PJ, Poline J-B, Lourdusamy A,
Banaschewski T, Barker GJ, Bellgrove MA, Büchel C,
Byrne M, Cummins TDR, Fauth-Bühler M, Flor H,
Gallinat J, Heinz A, Ittermann B, Mann K, Martinot J-L,
Lalor EC, Lathrop M, Loth E, Nees F, Paus T, Rietschel M,
Smolka MN, Spanagel R, Stephens DN, Struve M,
Thyreau B, Vollstaedt-Klein S, Robbins TW,
Schumann G, Garavan H, Imagen Consortium
(2012). Adolescent impulsivity phenotypes
characterized by distinct brain networks. Nature
Neuroscience 15, 920–925.
Wu YH, Gau SS, Lo YC, Tseng WY (2014). White matter
tract integrity of frontostriatal circuit in attention deficit
hyperactivity disorder: association with attention
performance and symptoms. Human Brain Mapping 35,
199–212.