Brain Imaging and Behavior (2014) 8:588597

DOI 10.1007/s11682-013-9275-7

ORIGINAL RESEARCH

Differences in functional activity between boys with pure

oppositional defiant disorder and controls during a response
inhibition task: a preliminary study
Yan Zhu & Kui Ying & Ji Wang & Linyan Su &
Jingyuan Chen & Fan Lin & Dongyang Cai & Ming Zhou &
Daxing Wu & Courtney Guo & Shi Wang

Published online: 4 January 2014

# Springer Science+Business Media New York 2014

Abstract Functional Magnetic Resonance Imaging (fMRI)
of inhibitory control has only been investigated in patients
with attention deficit hyperactivity disorder (ADHD) and
conduct disorder (CD). The objective of this study was to
investigate the differences of functional areas associated with
inhibitory control between boys with pure oppositional defiant
disorder (ODD) and controls during a response inhibition task
using functional magnetic resonance imaging (fMRI). Eleven
boys with pure ODD and ten control boys, aged 10 to 12,
performed a GoStop response inhibition task in this study. The
task has a series of go trials to establish a pre-potent
response tendency and a number of stop trials to test
subjects ability to withhold their responses. During the
GoStop task, greater activation in the dorsolateral parts of
the bilateral inferior frontal gyrus, left middle frontal gyrus
(lMFG) and right superior frontal gyrus (rSFG) activation was
seen in the ODD boys. Additionally, reduced activation in
regions of the right inferior frontal gyrus (rIFG) was seen in
the ODD boys in comparison with the control group. The
results may suggest that the higher activation in areas adjacent
to the rIFG could be the cause of reduced activation in the
rIFG; although this is speculative and requires additional
supporting evidence. The findings further suggest that ODD
is a less pronounced functional disorder compared to ADHD
and CD.

Y. Zhu
Psychiatry Department, Yu Quan Hospital, Tsinghua University Keywords Oppositional defiant disorder (ODD) . Right
School of Medicine, Beijing, China inferior frontal gyrus (rIFG) . Functional magnetic resonance
imaging (fMRI) response inhibition task
Y. Zhu : M. Zhou
Institute of Neurological Disorders, Tsinghua University School of
Medicine, Beijing, China
Introduction
K. Ying (*) : D. Cai : S. Wang
Department of Engineering Physics, Tsinghua University,
Beijing 100084, China Oppositional defiant disorder (ODD) was first defined in 1980
e-mail: kuiying2012@gmail.com in the DSM-III (Diagnostic and statistical manual, 3rd edition;
American Psychiatric Association, 1980). The defining fea-
J. Wang : J. Chen : F. Lin
Department of Biomedical Engineering, Tsinghua University,
ture of ODD is a recurrent pattern of negativistic, defiant,
Beijing, China disobedient, and hostile behavior towards authority figures
(Loeber et al. 2000; Lavigne et al. 2001; Van Goozen et al.
M. Zhou 2000; Zhu et al. 2005). ODD continues to be the most com-
Anesthesia Department, Yu Quan Hospital, Tsinghua University
mon juvenile disorder seen in mental health and community
School of Medicine, Beijing, China
clinics and is of great concern because of its high degree of
L. Su : D. Wu impairment and poor prognosis. Attention-deficit hyperactiv-
Mental Health Institute, Second Xiangya Hospital, Central South ity disorder (ADHD), conduct disorder (CD), anxiety and
University, 139 Renmin Road, Changsha, China
mood disorders, somatoform disorder, and substance abuse
C. Guo are common comorbid conditions of ODD (Speltz et al. 1999;
International School of Beijing, Beijing, China Loeber et al. 2000; Lavigne et al. 2001; Loeber and Birmaher
Brain Imaging and Behavior (2014) 8:588597
2002). Furthermore, multiple studies suggest that ODD could
potentially be the early stage of more serious mental disorders
that have been linked to juvenile crimes. More specifically,
studies show that about 30 % of children with ODD later
develop CD, and about 20 % of those with CD later meet
criteria for antisocial personality disorder (APD); additionally,
about 15 % of adolescents with APD later get involved in
juvenile crimes. Therefore, various studies infer that ODD,
CD, and APD may be hierarchically and developmentally
related (Biederman et al. 1996; Loeber et al. 2000;
Kuperman et al. 2001).
Behavioral disorders usually have a corresponding neurobio-
logical basis, and are typically the manifestation of disturbances
in brain function (Hendren et al. 2000). A review of studies on
response inhibition from various disciplines, including human
psychology, psychiatry and animal behavior, suggests that mul-
tiple neurochemical mechanisms can influence response inhibi-
tion, and that impulsive behavior has no unique neurobiological
basis (Barratt and Slaughter 1998; Evenden 1999; Nigg 2000).
There is considerable controversy in neuropsychological
research differentiating ADHD from ODD/CD. Barkley et al.
proposed that a deficit in behavioral inhibition, as the primary
executive self-regulatory act necessary for performing other
executive functions (EF), is the core deficit of ADHD
(Barkley 1997). Poor inhibitory performance has been shown
in some studies to be specifically related to ADHD and not to
CD (Schachar and Tannock 1995). The evidence for EF
deficits in CD or ODD is not very strong and it therefore
remains unclear whether EF deficits are specifically related to
ADHD or are also evident in children with ODD and comor-
bid ODD plus ADHD (Hill 2002). Some evidence shows
impaired inhibitory control and working memory in ADHD,
ODD and/or CD in the school-aged years (Castellanos et al.
2006; Martinussen et al. 2005; Oosterlaan et al. 2005). Some
studies of school-aged children have concluded that inhibitory
control is not specifically related to ADHD, but is also a
neuropsychological correlate of ODD and CD (Oosterlaan
et al. 1998; Sergeant et al. 2002). Karin et al. found that the
relations between measures of inhibitory control and ODD
were eliminated upon adjusting for ADHD symptoms. Some
research groups reported that adolescents with ADHD, CD,
and ODD exhibited higher commission error rates or lower
response inhibition rates during the tasks from the rapid-
decision paradigm (Oosterlaan et al. 1998; Bjork et al. 2002;
Marsh et al. 2002; Swann et al. 2002; Dougherty et al. 2003).
Our previous studies also showed that pure ODD boys had
high error rates, lower percentages of inhibited responses and
longer latencies than the control group during GoStop Task
performance (Zhu et al. 2008). In summary, there is evidence
in both directions, i.e., the inhibitory deficits of children with
CD/ODD are either much less than those of children with
ADHD or not different from those of the no diagnosis control
population. Therefore, further research is needed.
589
Functional Magnetic Resonance Imaging (fMRI) has been
widely used to study response inhibition. Previous fMRI
studies have localized a wide arrange of brain activation
regions by using blocks of go or mixed go/stop trials. These
areas include prefrontal and cingulate cortices, basal ganglia,
and cerebellum (Menon et al. 2001; Rubia et al. 2003; Li et al.
2006). Menon et al. found greater activation areas during the
mixed go/stop than the go task in bilateral dorsolateral pre-
frontal, inferior frontal, inferior parietal gyri, bilateral caudate
nuclei, and right anterior cingulate cortex. Rubia et al. (2003,
2005, 2007a, b) concluded that the right prefrontal cortex,
specifically the right inferior frontal gyrus (rIFG), plays a
critical role in mediating response inhibition. Aron et al.
(2003, 2004; Aron and Poldrack 2005) reported that patients
with damage to the right prefrontal cortex showed lengthened
stop-signal reaction times compared with healthy controls,
whereas patients with left hemisphere lesions did not. Hamp-
shire et al. (2010) further clarified the role of the rIFG during a
particular form of executive control referred to as response
inhibition, and revealed that the rIFG was recruited when
important stop-signal cues were detected, regardless of wheth-
er the detection was followed by inhibition or generation of a
response. Other works suggest that the subthalamic nucleus, a
region in the basal ganglia, may also be involved in aspects of
response inhibition (Aron and Poldrack 2006). Some investi-
gators speculated that the rIFG may exert top-down effects on
inhibition via connections to the subthalamic nucleus and are
presently following up on these findings using diffusion ten-
sor imaging to assess white matter tract connectivity between
brain regions (Behrens et al. 2003). Recent research groups
have found that the Inferior Frontal Cortex (IFC) is part of the
ventral attention system (Chao et al. 2009; Duann et al. 2009).
By increasing activity in response to the stop signal (a behav-
iorally relevant external stimulus), the IFC may serve to orient
attention and processing resources including those related to
inhibitory control to the stop process and, as a result, facilitate
stop signal inhibition. Chao et al. (2009) confirmed greater
preSMA but not rIFC activity during short as compared to
long SSRT (stop signal reaction time) session within individ-
uals. Interestingly, consistent with bilateral IFC activation
during stop success as compared to stop error, recent work
showed increased no-go errors in patients with left IFC lesions
(Chao et al. 2009).
At present, major research about response inhibition with
disruptive behavior disorder (DBD) has been focused on
ADHD. Some fMRI studies in adolescents with ADHD
attempted to determine the neural basis for DBD that hap-
pened at a young age. It was found that ADHD is associated
with brain abnormalities in the inhibition-mediating inferior
and dorsolateral prefrontal cortex, the cingulate, and the cau-
date (Booth et al. 2005; Rubia et al. 2005; Durston et al. 2006;
Pliszka et al. 2006; Konrad et al. 2006). There have been
fewer fMRI studies on CD, a disorder of proactive aggression
590
and antisocial behavior, since CD overlaps clinically, behav-
iorally, and cognitively with ADHD. Rubias research group
(2008) used event-related fMRI to compare brain activation of
boys with noncomorbid ADHD and boys with noncomorbid
CD during an individually-adjusted tracking stop task that
measures inhibition and stopping failure. They found that
inhibition-mediating prefrontal regions appear to be reduced
in ADHD, while regions in posterior temporal-parietal, per-
formance monitoring networks are reduced in CD. Rubias
research group (2009a, b, c) also used a rewarded continuous-
performance task that measured sustained attention to com-
pare brain regions of boys with pure ADHD and pure CD.
Attention-related dysfunction in the ventrolateral prefrontal
cortex was seen in ADHD patients, and reward-related dys-
function in the orbitofrontal cortex was seen in conduct dis-
order patients. Among these studies, two types of tasks were
mainly used in the rapid-decision paradigm of studying im-
pulsivity: continuous performance tests (CPT), and stop tasks.
In the CPT, impulsive responding is defined as a response to a
particular stimulus that is similar to the designated task. In
contrast, the stop task assesses an individuals ability to inhibit
an already-initiated motor response to a target stimulus. Thus,
in the stop task, impulsivity response is defined as the inability
to withhold those responses. Hummer et al. found that teens
with DBD and ADHD performed worse on both
neurocognitive and questionnaire measures of executive func-
tion than the DBD without ADHD. This indicates that sub-
groups of DBD may exist depending on the presence or
absence of comorbid ADHD (Hummer et al. 2011).
Since the occurrence rate of pure ODD is low, it is difficult
to collect adequate data from subjects with pure ODD. To the
authors knowledge, there has been no published investigation
of whether pure ODD by itself demonstrates impulsive control
dysfunction. Therefore, the goal of our study is to use fMRI to
investigate the difference of functional response to inhibitory
control between boys with pure ODD and controls. We wish
to understand if pure ODD can demonstrate dysfunctional
impulse behavior without the presence of other disorders,
and how its functional response shown on fMRI-BOLD im-
ages is different from that of ADHD and CD. In our study,
pure ODD teenaged boys do not have problems of ADHD,
CD and other disorders that meet the requirements of DSM IV
diagnosis.
Materials and methods
Subjects
Over 2,500 students were selected from a middle school in
Changsha, Hunan province in China between June 2004 and
September 2004. Questionnaires were prepared according to
the diagnostic criteria for every student to check on all mental
Brain Imaging and Behavior (2014) 8:588597
disorders (ADHD, CD, ODD, etc.) in the DSM-IV (Diagnos-
tic and statistical manual, 4th edition; American Psychiatric
Association, 1994). Parents and teachers were asked to give a
yes or no answer to the presence of the 8 symptoms listed.
Positive cases were identified when 4 or more symptoms were
reported to be present and lasting for more than 6 months.
These students were then interviewed and selected into the
ODD group by three clinical psychiatrists (Linyan Su, Yan
Zhu, Daxing Wu), using the diagnostic criteria for ODD in the
DSM-IV and the information provided by the parents and
teachers. Patients were not considered for participation if they
met any of the following exclusionary criteria: 1) ADHD, 2)
CD, 3) anxiety and mood disorders, 4) somatoform disorder,
5) substance abuse according to the DSM-IV, 6) use of alcohol
or drugs or medication. Among the 213 boys selected into the
ODD group, 107 boys were diagnosed with CD, 32 boys were
diagnosed with ADHD, and 4 boys were diagnosed with other
mental diseases. The remaining 70 boys in the presence of
borderline ODD were selected as the pure ODD group. As a
matter of fact, there are no absolute pure ODD subjects
because some inattentive and/or hyperactive impulse symp-
toms of ADHD are unable to be observed in clinic. Therefore,
here pure ODD means relatively pure ODD. Control subjects
were 70 normal boys. Every single child went through the
questionnaire screen including ADHD, CD, ODD, and im-
pulse and emotion disorders. Only those who were not cate-
gorized into any disorder group were considered as the con-
trols. The control subjects have no history of any mental or
neurological disorders, and no history of drug-or substance-
abuse. Controls then went through clinical interviews by
experienced child psychiatrists for final selection.
Among the 140 potential participants, 11 ODD boys (aged
from 10 to 12, average 11.5) and 10 control boys (aged from
10 to 13, average 11.7) volunteered to take part in the study.
All ODD and control subjects were from the same school,
right-handed, with normal intelligence (IQ>80,there is no
statistical difference in IQ for two groups) and normal eye-
sight (not wearing corrective lenses). The study was approved
by the Ethics Committee of Central South University and the
Ministry of Health of China. Formal consent forms for partic-
ipation were signed by the parents or guardians.
GoStop task
The present study chose GoStop Task (Dougherty et al. 2003,
GoStop version 1.0 manual provided by Doughertys group,
2003) to test an individuals abilities for response inhibition.
The fMRI task utilized a block design. For one task block,
there were 30 trials consisting of three types of trials - Stop
trials, Go trials, and Novel trials. Each trial consisted of a
randomly generated 5-digit number presented for 500 ms,
interleaved with a 500 ms off period. As Fig. 1 shows, the
Stop trials were those instances when a number that was
Brain Imaging and Behavior (2014) 8:588597
Fig. 1 Diagram of GoStop task
identical to the previous number changed from black to red
and the participant was instructed to inhibit responding. The
Go trials were those instances when a number that was iden-
tical to the previous number appeared and remained black. For
these trials, the participant was instructed to respond by press-
ing the mouse button with a right index finger. The Novel
trials were non-matching numbers presented in black. The
participant was instructed not to respond to non-matching
numbers. There was at least one Novel stimulus (No signal
referred in Fig. 1) following every Stop and Go trial. Among
the 30 trials, there were 8 Go trials, 8 Stop trials, and 14 Novel
trials. The stop trials started with go signals, i.e., a portion of
go signals (50 % of total go and stop signals) was unpredict-
ably followed by a stop signal (the color of the number
changed to red in this case), which signaled the participant to
withhold his/her response. The duration that the identical
number remains black before turning red had an equal prob-
ability of being one of four delay times: 50, 150, 250 or
350 ms. The experiment consisted of two types of blocks:
the Task condition and the Control condition (basically rest-
ing), each taking 30 trials. The experiment started with a
preparation period of 12 s, followed by five cycles with each
cycle of 60 s alternating Task and Control conditions to cover
the 5 min- and 12 s- session. Before the start of the fMRI scan,
each subject was required to take the same GoStop task
outside the scan room to obtain behavioral datathe mea-
surements of the percentage of inhibited responses and the
stop latency.
Table 1 Stop latency and per-
centage of inhibited responses Delay Stop latency (ms)
ODD group
50 ms 413.61106.56
150 ms 350.45148.77
250 ms 222.14124.81
350 ms 126.11149.93
591
Image acquisition
The experiment was performed using a 1.5 T GE Signa
scanner with a quadrature head coil at the Second Hospital
of South Central University in China. The structural images
were acquired using Spin Echo sequence in real time image
processing (RTIP) parallel to the anterior/posterior commis-
sure (AC/PC) plane with the following parameters: number of
slices (NS)=18; repetition time (TR)/echo time (TE)/slice
thickness (ST)=10s/10ms/5 mm; field of view (FOV)/matrix
size=240*240 mm2/256*256. Functional BOLD images were
then acquired with a single-shot echo-planar imaging (EPI)
sequence with the following parameters: TR/TE/ST=2 s/
60 ms/5 mm, and the FOV is 240*240 mm2 with a matrix
size of 64*64. There were 150 images per slice acquired.
fMRI data pre-processing
The first 12-s preparation period was removed from the whole
scan. FMRI data was pre-processed using Statistical Paramet-
ric Mapping (SPM5, www.fil.ion.ucl.ac.uk/spm). Digital
Imaging and Communications in Medicine (DICOM) images
were first converted to a Multivolume Analyze format. All
anatomical and echo-planar images were pre-processed
through the following procedures: realignment of functional
echo-planar images was applied to correct slight head move-
ments between scans; slice timing was carried out to correct
the differences in acquisition time between slices; individual
images were normalized to an EPI template, with parameters
based on the mean functional image and the age range of
subjects; the images were smoothed by convolution with an
isotropic Gaussian kernel having a FWHM of (8,8,10 mm^3),
twice the size of the voxel.
Individual analysis
In the first step of individual analysis, a voxel-by-voxel gen-
eral linear model (GLM) (Friston et al. 1995) was used for
each subject to obtain the Task signal minus the Control
signal. The design matrix was generated according to the
experiment conditions, and the expected hemodynamic re-
sponse at stimulus onset for each block was modeled by a
Percentage of inhibited responses
Control group ODD group Control group
346.0972.58 58 % 77 %
248.7868.27 57 % 73 %
137.2178.59 55 % 68 %
81.8672.06 50 % 65 %
592
Fig. 2 Activation regions for the
control group (p <0.001, cluster
size is 50 voxels above)
canonical hemodynamic response function (HRF). Therefore
the convolution of the experiment matrix and the HRF result-
ed in the final design matrix. Maps of the parameter estima-
tions of individual subjects were generated by t-test, with a
significance level of p <0.001 with cluster size of 50 voxels
above. Afterwards, the parameter maps were submitted to
second-level analysis for determining the activation differ-
ences at the group level.
ROI analysis
First, a random-effect analysis across the whole brain was
used to determine which brain regions showed task-related
increases in activity. Consistent with prior studies, the
inhibition-mediating prefrontal regions showed significant ac-
tivations during the response inhibition task. We selected
those regions as a region of interest (ROI) for later group-
level analysis.
In ROI analysis we used the WFU PickAtlas (tool version
2.4), which is available as a tool embedded in SPM5. The
whole-brain analysis was conducted to calculate the correla-
tion coefficients between each pixel of the brain and the
chosen ROI.
Group level analysis
There were two parts for the group-level analysis. One was a
one-sample t-test, which calculated the parameter estimation
of subjects within the same group. At this level, we estimated
the parameters for each voxel based on the Gaussian distribu-
tion. The averaged activation regions were overlaid on the T1
template, and the statistical results including t-scores, cluster
sizes, and localization in MNI-labeled space of the voxels in
these areas were reported accordingly. The other group-level
Fig. 3 Activation regions for the
ODD group (p <0.001, cluster
size is 50 voxels above)
Brain Imaging and Behavior (2014) 8:588597
analysis was a two-sample t -test for comparison of two
groups. In this test, we compared regions with significant
activations in Task condition between the ODD group and
the control group. The results were also shown at the signif-
icance level of p <0.001 with cluster size of 50 voxels above
for both the ODD group > Control group and the Control
group > ODD group conditions.
Results
Behavioral data
One important variable that the GoStop task measures is the
Stop latency, which is the time between Stop Signal onset and
the response. The other primary measure is the accuracy rate
of inhibited responses, i.e., the percentage of Stop trials where
no response occurs. Table 1 shows the two measurements for
the ODD group and control group with four different types of
Stop trials, i.e., different delays. The ODD group showed
lower accuracy rate for inhibited responses, meaning that they
have higher error rate during response inhibition. The ODD
group had longer stop latency for all 4 types of delays. This
indicates that the ODD group took longer time to inhibit the
already-initiated responses. Healthy controls took less time to
inhibit response when they found they were wrong.
Activation regions in a single group during the GoStop task
We compared brain activation regions for the control group
and ODD group. Figure 2 showed the results from a one
sample t-test for the control group at a statistical threshold of
p =0.001. The activation regions included the bilateral inferior
frontal gyrus, the right middle frontal gyrus, and the insula. In
Brain Imaging and Behavior (2014) 8:588597 593

Table 2 Location, size, T-value,

and label of the task-activated Group x, y, z(mm) T-value Cluster size Side Brain region
brain regions for both groups
ODD Group 30 26 6 5.06 111 R Inferior Frontal Gyrus
38 24 8 5.02
32 30 2 5.05 101 L Inferior Frontal Gyrus
40 42 34 4.81 67 R Middle Frontal Gyrus
Control Group 40 22 0 20.67 90 L Inferior Frontal Gyrus
40 26 8 13.73
42 36 46 12.04 102 R Middle Frontal Gyrus
50 32 38
40 16 10 11.76 141 R Insula
48 48 6 10.77 69 R Inferior Frontal Gyrus

comparison, Fig. 3 shows results from a one sample t-test for itself. Accordingly, to date there is no published study of
the ODD group. The response inhibition was associated with whether ODD by itself can demonstrate impulse behavior
activation areas in the bilateral inferior frontal gyrus and the dysfunction. fMRI can help us to better understand the neural
right middle frontal gyrus. The artificial color bar represents correlates of pure ODD, and how this disorder differs from
the magnitude of t-scores, and the colored regions indicate a t pure ADHD and pure CD. Because ODD can be a precursor
score above the statistical threshold with a cluster size of more for CD and other anti-social problems, our study on pure ODD
than 50 voxels. Table 2 summarizes the location, size and using fMRI may provide insights for measures to prevent more
statistical t values of those activation regions. severe antisocial problems from occurring. In the present
study, we first employed an inhibition response task (GoStop
task) to study the neurobiological network associated with
Between-group differences
response inhibition in boys with pure ODD and controls, and
recorded the BOLD signal fluctuation in the brain over the
The task-related activation regions of the two groups overlap-
course of the experiment using fMRI. Both the ODD group
ped primarily with each other in the inferior frontal gyrus,
and the control group showed significant activation in the right
indicating that this region plays a critical role in the neural
inferior frontal cortex and the right middle frontal cortex.
basis of response inhibition. In order to display the group
differences between ODD boys and controls, a two-sample
t-test was used, and the comparison was made in two direc-
tions: ODD > Control, and Control > ODD. Figure 4 (left)
shows that during the GoStop task, the ODD group displayed
greater activation in the dorsolateral parts of the bilateral
inferior frontal gyrus, the left middle frontal gyrus and the
right superior frontal gyrus than the control group displayed.
The right images in Fig. 4 show that the region in the right
inferior frontal gyrus tends to be activated more in the control
group than in the ODD group. Table 3 summarizes the loca-
tion, size and statistical values of the regions listed above.

Discussion

Currently, there is a large body of studies on impulsive behav-

ior for comorbid ADHD/CD with ODD. However, from these
studies it is unclear whether the impulse control problem is
caused by pure ODD or in conjuction with other disorders.
Other studies have examined the behavior problem associated
with pure ADHD or pure CD. Since the occurrence rate of pure Fig. 4 Brain regions in group differences for ODD > Control, and
ODD is low, it is difficult to study participants with ODD by Control > ODD. (p <0.001, cluster size is 50 voxels above)
594 Brain Imaging and Behavior (2014) 8:588597

Table 3 Location, size, T-value,

and label of the task-activated Group x, y, z(mm) T-value Cluster size Side Brain region
brain regions for the group
differences ODD > Control 44 42 38 5.66 170 R Superior Frontal Gyrus
36 22 14 5.09 322 R Inferior Frontal Gyrus
32 28 2 4.55
40 22 0 4.98 153 L Inferior Frontal Gyrus
32 32 2 4.35
36 40 22 4.19 329 L Middle Frontal Gyrus
26 32 20 3.94
Control > ODD 40 20 6 5.57 118 R Inferior Frontal Gyrus

There are currently two viewpoints regarding IFC function.
Some research groups postulate rIFG and some of the periph-
eral systems play a major role in response inhibition (Garavan
et al. 1999; Konishi et al. 2002; Li et al. 2006; Rubia et al.
2005, 2007a, b), while others believe IFC is part of the ventral
attention system (Chao et al. 2009; Duann et al. 2009;
Hampshire et al. 2010).
Activation regions for both ODD and the controls were
compared in two directions (ODD > Control, and Control >
ODD). From Fig. 5a, the colored area centered at (40, 20, 6),
represents the reduced activation region in ODD boys, while
the area in Fig. 5b, centered at (36, 22, 14) and (32, 28, 2),
represents greater activation in ODD boys. Compared with the
same template, Fig. 5c depicts the location differences be-
tween the areas in Fig. 5a and b. These results suggest that a
portion of rIFG in ODD boys has a lower regional activity
level and poorer capacity for inhibition response, assuming
that IFC plays a major role in response inhibition. Meanwhile,
other brain regions, especially adjacent cortices such as dor-
solateral parts of the bilateral inferior frontal gyrus and middle
or superior frontal gyrus exhibited higher activation in ODD
boys. According to Lis research results, the decreased activity
in rIFG in the ODD group may indicate that pure ODD
subjects have an attention problem, i.e., the ability of atten-
tional monitoring and allocation of processing resources is
lower than for the controls. It was also found that regions in
right superior and inferior frontal gyrus, and left inferior and
middle frontal gyrus have greater activity than controls. This
indicates that pure ODD subjects are less impaired in response
inhibition, but have more impairment in attention. The most
consistent finding in fMRI literature for ADHD is that ADHD
patients have under-activation of the bilateral inferior prefron-
tal cortex when completing tasks of inhibitory and cognitive
control (Silk et al. 2005; Pliszka et al. 2006; Rubia et al. 2005,
2008). Unlike the findings of previous ADHD studies, only
the part of rIFG in ODD boys showed significant under-
activation during response inhibition in the current study.
The higher activation in adjacent brain regions found in
ODD boys was probably recruited to make up some reduced
activation in the rIFG; although this is speculative and requires
additional supporting evidence.
Compared to CD, disorder-specific abnormalities were re-
ported in boys with CD in the paralimbic system comprising
orbitofrontal and temporo-limbic regions during sustained

Fig. 5 Brain regions in group

differences at different slice
locations. a Control > ODD; b
a
ODD > Control; c the
superimposed regions of (a) on
(b). (p <0.001, cluster size is 50
voxels above)

c
Brain Imaging and Behavior (2014) 8:588597
attention, inhibition and reward (Rubia et al. 2008, 2009a, b).
Rubia first found that the temporal and parietal brain regions are
dysfunctional in CD and, furthermore, that these dysfunctions
are specific to children with CD in the context of inhibitory
control. However, this study did not find significant dysfunc-
tions in temporal or parietal areas as shown in previous CD
literature. A reasonable explanation for this inconsistency is that
the current study investigated different psychiatric disorders,
and dysfunctions in the parietal and temporal regions of ODD
patients during inhibition response are not so pronounced as to
be observed. Therefore, this finding suggests that ODD might
be a less severe cognitive disorder compared to CD.
The behavioral problems of children diagnosed with DBD
but no comorbid disorder involving executive functioning
may be more strongly influenced by amilial/environmental
factors or by verbal limitations and attributional biases
(Hummer et al. 2011). The trend for more PIY-reported family
problems in the DBD in absence of ADHD group compared to
DBD in presence of ADHD teens underlines this possibility,
although the family stress of DBD in general (regardless of
ADHD comorbidity) also likely influences this result (both
groups differ from controls) (Hummer et al. 2011). Poor
modeling by parents or other authority figures, negative or
inconsistent discipline (Snyder et al. 1997), and social cogni-
tion impairments (Dodge 1993) may play a more significant
role in the etiology of DBDs, especially when ADHD is
absent. Treatment of disruptive behavior disorder in these
youths may be more appropriately focused on behavioral
and social-cognitive factors as opposed to impulsivity and
poor self-control. The results of behavior study on DBD
without ADHD aligned with our pure ODD neuroimaging
findings, i.e., our results show that ODD has less degree of
functional disorder.
The GoStop task (Dougherty et al. 2003) was used in this
study where the go and stop signals were mixed equally.
However, the stop signals were always preceded with go
signals, i.e., some portion of go (50 % of all go and stop
signals) signals were followed by a stop signal, which
signaled the participant to withhold the response. According
to Li et al.s paper (2006), the number of go signals should be
much more (at least two times) than that of stop signals in a
stop task in order to measure an already- initiated motor
response. The go signals help to build up a pre-potent re-
sponse tendency, where stop signals are for participants to
withhold the responses. In the task we used, it can be consid-
ered that the number of go signals was twice that of the
number of stop signals since the stop signals always
started with the go signals. In this way, the GoStop task
assessed an individuals ability to inhibit an already-initiated
motor response to a target stimulus. However, if we consider
go signals and stop signals as two separate types of
signals, our task has lower inhibitory load than what Li group
recommended. This might be a limitation in the study.
595
Meanwhile, we collected fMRI data from 11 pure ODD boys
who were selected from thousands of boys with similar edu-
cation backgrounds. The difficulty in finding pure ODD boys
resulted in a relatively small sample size, which is admittedly
another limiting factor in this study.
During the selection of boys with pure ODD, we did not
further diagnose if any participant had attention problems (but
not reaching ADHD severity since ADHD is excluded). These
symptoms at the sub-clinical level can be related to neuropsy-
chological deficits and need to be controlled dimensionally by
using ADHD and/or ODD symptoms as a covariate. Other-
wise, this could have helped us better clarify if ODD results in
reduced inhibitory control capability or simply an attention
problem, considering that there are currently two viewpoints
regarding IFC function.
Conclusion
To our knowledge, this is the first fMRI study of pure ODD
boys using a response inhibition task. We found that ODD
participants showed significantly reduced activation in the
rIFG, but higher activation in adjacent areas such as dorsolat-
eral parts of the bilateral inferior frontal gyrus and middle or
superior frontal gyrus. We further inferred that ODD is a less
pronounced functional disorder compared to ADHD and CD.
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