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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) subjects ability to withhold their responses. During the
of inhibitory control has only been investigated in patients GoStop task, greater activation in the dorsolateral parts of
with attention deficit hyperactivity disorder (ADHD) and the bilateral inferior frontal gyrus, left middle frontal gyrus
conduct disorder (CD). The objective of this study was to (lMFG) and right superior frontal gyrus (rSFG) activation was
investigate the differences of functional areas associated with seen in the ODD boys. Additionally, reduced activation in
inhibitory control between boys with pure oppositional defiant regions of the right inferior frontal gyrus (rIFG) was seen in
disorder (ODD) and controls during a response inhibition task the ODD boys in comparison with the control group. The
using functional magnetic resonance imaging (fMRI). Eleven results may suggest that the higher activation in areas adjacent
boys with pure ODD and ten control boys, aged 10 to 12, to the rIFG could be the cause of reduced activation in the
performed a GoStop response inhibition task in this study. The rIFG; although this is speculative and requires additional
task has a series of go trials to establish a pre-potent supporting evidence. The findings further suggest that ODD
response tendency and a number of stop trials to test 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 589

2002). Furthermore, multiple studies suggest that ODD could Functional Magnetic Resonance Imaging (fMRI) has been
potentially be the early stage of more serious mental disorders widely used to study response inhibition. Previous fMRI
that have been linked to juvenile crimes. More specifically, studies have localized a wide arrange of brain activation
studies show that about 30 % of children with ODD later regions by using blocks of go or mixed go/stop trials. These
develop CD, and about 20 % of those with CD later meet areas include prefrontal and cingulate cortices, basal ganglia,
criteria for antisocial personality disorder (APD); additionally, and cerebellum (Menon et al. 2001; Rubia et al. 2003; Li et al.
about 15 % of adolescents with APD later get involved in 2006). Menon et al. found greater activation areas during the
juvenile crimes. Therefore, various studies infer that ODD, mixed go/stop than the go task in bilateral dorsolateral pre-
CD, and APD may be hierarchically and developmentally frontal, inferior frontal, inferior parietal gyri, bilateral caudate
related (Biederman et al. 1996; Loeber et al. 2000; nuclei, and right anterior cingulate cortex. Rubia et al. (2003,
Kuperman et al. 2001). 2005, 2007a, b) concluded that the right prefrontal cortex,
Behavioral disorders usually have a corresponding neurobio- specifically the right inferior frontal gyrus (rIFG), plays a
logical basis, and are typically the manifestation of disturbances critical role in mediating response inhibition. Aron et al.
in brain function (Hendren et al. 2000). A review of studies on (2003, 2004; Aron and Poldrack 2005) reported that patients
response inhibition from various disciplines, including human with damage to the right prefrontal cortex showed lengthened
psychology, psychiatry and animal behavior, suggests that mul- stop-signal reaction times compared with healthy controls,
tiple neurochemical mechanisms can influence response inhibi- whereas patients with left hemisphere lesions did not. Hamp-
tion, and that impulsive behavior has no unique neurobiological shire et al. (2010) further clarified the role of the rIFG during a
basis (Barratt and Slaughter 1998; Evenden 1999; Nigg 2000). particular form of executive control referred to as response
There is considerable controversy in neuropsychological inhibition, and revealed that the rIFG was recruited when
research differentiating ADHD from ODD/CD. Barkley et al. important stop-signal cues were detected, regardless of wheth-
proposed that a deficit in behavioral inhibition, as the primary er the detection was followed by inhibition or generation of a
executive self-regulatory act necessary for performing other response. Other works suggest that the subthalamic nucleus, a
executive functions (EF), is the core deficit of ADHD region in the basal ganglia, may also be involved in aspects of
(Barkley 1997). Poor inhibitory performance has been shown response inhibition (Aron and Poldrack 2006). Some investi-
in some studies to be specifically related to ADHD and not to gators speculated that the rIFG may exert top-down effects on
CD (Schachar and Tannock 1995). The evidence for EF inhibition via connections to the subthalamic nucleus and are
deficits in CD or ODD is not very strong and it therefore presently following up on these findings using diffusion ten-
remains unclear whether EF deficits are specifically related to sor imaging to assess white matter tract connectivity between
ADHD or are also evident in children with ODD and comor- brain regions (Behrens et al. 2003). Recent research groups
bid ODD plus ADHD (Hill 2002). Some evidence shows have found that the Inferior Frontal Cortex (IFC) is part of the
impaired inhibitory control and working memory in ADHD, ventral attention system (Chao et al. 2009; Duann et al. 2009).
ODD and/or CD in the school-aged years (Castellanos et al. By increasing activity in response to the stop signal (a behav-
2006; Martinussen et al. 2005; Oosterlaan et al. 2005). Some iorally relevant external stimulus), the IFC may serve to orient
studies of school-aged children have concluded that inhibitory attention and processing resources including those related to
control is not specifically related to ADHD, but is also a inhibitory control to the stop process and, as a result, facilitate
neuropsychological correlate of ODD and CD (Oosterlaan stop signal inhibition. Chao et al. (2009) confirmed greater
et al. 1998; Sergeant et al. 2002). Karin et al. found that the preSMA but not rIFC activity during short as compared to
relations between measures of inhibitory control and ODD long SSRT (stop signal reaction time) session within individ-
were eliminated upon adjusting for ADHD symptoms. Some uals. Interestingly, consistent with bilateral IFC activation
research groups reported that adolescents with ADHD, CD, during stop success as compared to stop error, recent work
and ODD exhibited higher commission error rates or lower showed increased no-go errors in patients with left IFC lesions
response inhibition rates during the tasks from the rapid- (Chao et al. 2009).
decision paradigm (Oosterlaan et al. 1998; Bjork et al. 2002; At present, major research about response inhibition with
Marsh et al. 2002; Swann et al. 2002; Dougherty et al. 2003). disruptive behavior disorder (DBD) has been focused on
Our previous studies also showed that pure ODD boys had ADHD. Some fMRI studies in adolescents with ADHD
high error rates, lower percentages of inhibited responses and attempted to determine the neural basis for DBD that hap-
longer latencies than the control group during GoStop Task pened at a young age. It was found that ADHD is associated
performance (Zhu et al. 2008). In summary, there is evidence with brain abnormalities in the inhibition-mediating inferior
in both directions, i.e., the inhibitory deficits of children with and dorsolateral prefrontal cortex, the cingulate, and the cau-
CD/ODD are either much less than those of children with date (Booth et al. 2005; Rubia et al. 2005; Durston et al. 2006;
ADHD or not different from those of the no diagnosis control Pliszka et al. 2006; Konrad et al. 2006). There have been
population. Therefore, further research is needed. fewer fMRI studies on CD, a disorder of proactive aggression
590 Brain Imaging and Behavior (2014) 8:588597

and antisocial behavior, since CD overlaps clinically, behav- disorders (ADHD, CD, ODD, etc.) in the DSM-IV (Diagnos-
iorally, and cognitively with ADHD. Rubias research group tic and statistical manual, 4th edition; American Psychiatric
(2008) used event-related fMRI to compare brain activation of Association, 1994). Parents and teachers were asked to give a
boys with noncomorbid ADHD and boys with noncomorbid yes or no answer to the presence of the 8 symptoms listed.
CD during an individually-adjusted tracking stop task that Positive cases were identified when 4 or more symptoms were
measures inhibition and stopping failure. They found that reported to be present and lasting for more than 6 months.
inhibition-mediating prefrontal regions appear to be reduced These students were then interviewed and selected into the
in ADHD, while regions in posterior temporal-parietal, per- ODD group by three clinical psychiatrists (Linyan Su, Yan
formance monitoring networks are reduced in CD. Rubias Zhu, Daxing Wu), using the diagnostic criteria for ODD in the
research group (2009a, b, c) also used a rewarded continuous- DSM-IV and the information provided by the parents and
performance task that measured sustained attention to com- teachers. Patients were not considered for participation if they
pare brain regions of boys with pure ADHD and pure CD. met any of the following exclusionary criteria: 1) ADHD, 2)
Attention-related dysfunction in the ventrolateral prefrontal CD, 3) anxiety and mood disorders, 4) somatoform disorder,
cortex was seen in ADHD patients, and reward-related dys- 5) substance abuse according to the DSM-IV, 6) use of alcohol
function in the orbitofrontal cortex was seen in conduct dis- or drugs or medication. Among the 213 boys selected into the
order patients. Among these studies, two types of tasks were ODD group, 107 boys were diagnosed with CD, 32 boys were
mainly used in the rapid-decision paradigm of studying im- diagnosed with ADHD, and 4 boys were diagnosed with other
pulsivity: continuous performance tests (CPT), and stop tasks. mental diseases. The remaining 70 boys in the presence of
In the CPT, impulsive responding is defined as a response to a borderline ODD were selected as the pure ODD group. As a
particular stimulus that is similar to the designated task. In matter of fact, there are no absolute pure ODD subjects
contrast, the stop task assesses an individuals ability to inhibit because some inattentive and/or hyperactive impulse symp-
an already-initiated motor response to a target stimulus. Thus, toms of ADHD are unable to be observed in clinic. Therefore,
in the stop task, impulsivity response is defined as the inability here pure ODD means relatively pure ODD. Control subjects
to withhold those responses. Hummer et al. found that teens were 70 normal boys. Every single child went through the
with DBD and ADHD performed worse on both questionnaire screen including ADHD, CD, ODD, and im-
neurocognitive and questionnaire measures of executive func- pulse and emotion disorders. Only those who were not cate-
tion than the DBD without ADHD. This indicates that sub- gorized into any disorder group were considered as the con-
groups of DBD may exist depending on the presence or trols. The control subjects have no history of any mental or
absence of comorbid ADHD (Hummer et al. 2011). neurological disorders, and no history of drug-or substance-
Since the occurrence rate of pure ODD is low, it is difficult abuse. Controls then went through clinical interviews by
to collect adequate data from subjects with pure ODD. To the experienced child psychiatrists for final selection.
authors knowledge, there has been no published investigation Among the 140 potential participants, 11 ODD boys (aged
of whether pure ODD by itself demonstrates impulsive control from 10 to 12, average 11.5) and 10 control boys (aged from
dysfunction. Therefore, the goal of our study is to use fMRI to 10 to 13, average 11.7) volunteered to take part in the study.
investigate the difference of functional response to inhibitory All ODD and control subjects were from the same school,
control between boys with pure ODD and controls. We wish right-handed, with normal intelligence (IQ>80,there is no
to understand if pure ODD can demonstrate dysfunctional statistical difference in IQ for two groups) and normal eye-
impulse behavior without the presence of other disorders, sight (not wearing corrective lenses). The study was approved
and how its functional response shown on fMRI-BOLD im- by the Ethics Committee of Central South University and the
ages is different from that of ADHD and CD. In our study, Ministry of Health of China. Formal consent forms for partic-
pure ODD teenaged boys do not have problems of ADHD, ipation were signed by the parents or guardians.
CD and other disorders that meet the requirements of DSM IV
diagnosis. GoStop task

The present study chose GoStop Task (Dougherty et al. 2003,


Materials and methods GoStop version 1.0 manual provided by Doughertys group,
2003) to test an individuals abilities for response inhibition.
Subjects The fMRI task utilized a block design. For one task block,
there were 30 trials consisting of three types of trials - Stop
Over 2,500 students were selected from a middle school in trials, Go trials, and Novel trials. Each trial consisted of a
Changsha, Hunan province in China between June 2004 and randomly generated 5-digit number presented for 500 ms,
September 2004. Questionnaires were prepared according to interleaved with a 500 ms off period. As Fig. 1 shows, the
the diagnostic criteria for every student to check on all mental Stop trials were those instances when a number that was
Brain Imaging and Behavior (2014) 8:588597 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)
Fig. 1 Diagram of GoStop task
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.
identical to the previous number changed from black to red
and the participant was instructed to inhibit responding. The
fMRI data pre-processing
Go trials were those instances when a number that was iden-
tical to the previous number appeared and remained black. For
The first 12-s preparation period was removed from the whole
these trials, the participant was instructed to respond by press-
scan. FMRI data was pre-processed using Statistical Paramet-
ing the mouse button with a right index finger. The Novel
ric Mapping (SPM5, www.fil.ion.ucl.ac.uk/spm). Digital
trials were non-matching numbers presented in black. The
Imaging and Communications in Medicine (DICOM) images
participant was instructed not to respond to non-matching
were first converted to a Multivolume Analyze format. All
numbers. There was at least one Novel stimulus (No signal
anatomical and echo-planar images were pre-processed
referred in Fig. 1) following every Stop and Go trial. Among
through the following procedures: realignment of functional
the 30 trials, there were 8 Go trials, 8 Stop trials, and 14 Novel
echo-planar images was applied to correct slight head move-
trials. The stop trials started with go signals, i.e., a portion of
ments between scans; slice timing was carried out to correct
go signals (50 % of total go and stop signals) was unpredict-
the differences in acquisition time between slices; individual
ably followed by a stop signal (the color of the number
images were normalized to an EPI template, with parameters
changed to red in this case), which signaled the participant to
based on the mean functional image and the age range of
withhold his/her response. The duration that the identical
subjects; the images were smoothed by convolution with an
number remains black before turning red had an equal prob-
isotropic Gaussian kernel having a FWHM of (8,8,10 mm^3),
ability of being one of four delay times: 50, 150, 250 or
twice the size of the voxel.
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 Individual analysis
preparation period of 12 s, followed by five cycles with each
cycle of 60 s alternating Task and Control conditions to cover In the first step of individual analysis, a voxel-by-voxel gen-
the 5 min- and 12 s- session. Before the start of the fMRI scan, eral linear model (GLM) (Friston et al. 1995) was used for
each subject was required to take the same GoStop task each subject to obtain the Task signal minus the Control
outside the scan room to obtain behavioral datathe mea- signal. The design matrix was generated according to the
surements of the percentage of inhibited responses and the experiment conditions, and the expected hemodynamic re-
stop latency. sponse at stimulus onset for each block was modeled by a

Table 1 Stop latency and per-


centage of inhibited responses Delay Stop latency (ms) Percentage of inhibited responses

ODD group Control group ODD group Control group

50 ms 413.61106.56 346.0972.58 58 % 77 %
150 ms 350.45148.77 248.7868.27 57 % 73 %
250 ms 222.14124.81 137.2178.59 55 % 68 %
350 ms 126.11149.93 81.8672.06 50 % 65 %
592 Brain Imaging and Behavior (2014) 8:588597

Fig. 2 Activation regions for the


control group (p <0.001, cluster
size is 50 voxels above)

canonical hemodynamic response function (HRF). Therefore analysis was a two-sample t -test for comparison of two
the convolution of the experiment matrix and the HRF result- groups. In this test, we compared regions with significant
ed in the final design matrix. Maps of the parameter estima- activations in Task condition between the ODD group and
tions of individual subjects were generated by t-test, with a the control group. The results were also shown at the signif-
significance level of p <0.001 with cluster size of 50 voxels icance level of p <0.001 with cluster size of 50 voxels above
above. Afterwards, the parameter maps were submitted to for both the ODD group > Control group and the Control
second-level analysis for determining the activation differ- group > ODD group conditions.
ences at the group level.

ROI analysis Results

First, a random-effect analysis across the whole brain was Behavioral data
used to determine which brain regions showed task-related
increases in activity. Consistent with prior studies, the One important variable that the GoStop task measures is the
inhibition-mediating prefrontal regions showed significant ac- Stop latency, which is the time between Stop Signal onset and
tivations during the response inhibition task. We selected the response. The other primary measure is the accuracy rate
those regions as a region of interest (ROI) for later group- of inhibited responses, i.e., the percentage of Stop trials where
level analysis. no response occurs. Table 1 shows the two measurements for
In ROI analysis we used the WFU PickAtlas (tool version the ODD group and control group with four different types of
2.4), which is available as a tool embedded in SPM5. The Stop trials, i.e., different delays. The ODD group showed
whole-brain analysis was conducted to calculate the correla- lower accuracy rate for inhibited responses, meaning that they
tion coefficients between each pixel of the brain and the have higher error rate during response inhibition. The ODD
chosen ROI. group had longer stop latency for all 4 types of delays. This
indicates that the ODD group took longer time to inhibit the
Group level analysis already-initiated responses. Healthy controls took less time to
inhibit response when they found they were wrong.
There were two parts for the group-level analysis. One was a
one-sample t-test, which calculated the parameter estimation Activation regions in a single group during the GoStop task
of subjects within the same group. At this level, we estimated
the parameters for each voxel based on the Gaussian distribu- We compared brain activation regions for the control group
tion. The averaged activation regions were overlaid on the T1 and ODD group. Figure 2 showed the results from a one
template, and the statistical results including t-scores, cluster sample t-test for the control group at a statistical threshold of
sizes, and localization in MNI-labeled space of the voxels in p =0.001. The activation regions included the bilateral inferior
these areas were reported accordingly. The other group-level frontal gyrus, the right middle frontal gyrus, and the insula. In

Fig. 3 Activation regions for the


ODD group (p <0.001, cluster
size is 50 voxels above)
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. in rIFG in the ODD group may indicate that pure ODD
Some research groups postulate rIFG and some of the periph- subjects have an attention problem, i.e., the ability of atten-
eral systems play a major role in response inhibition (Garavan tional monitoring and allocation of processing resources is
et al. 1999; Konishi et al. 2002; Li et al. 2006; Rubia et al. lower than for the controls. It was also found that regions in
2005, 2007a, b), while others believe IFC is part of the ventral right superior and inferior frontal gyrus, and left inferior and
attention system (Chao et al. 2009; Duann et al. 2009; middle frontal gyrus have greater activity than controls. This
Hampshire et al. 2010). indicates that pure ODD subjects are less impaired in response
Activation regions for both ODD and the controls were inhibition, but have more impairment in attention. The most
compared in two directions (ODD > Control, and Control > consistent finding in fMRI literature for ADHD is that ADHD
ODD). From Fig. 5a, the colored area centered at (40, 20, 6), patients have under-activation of the bilateral inferior prefron-
represents the reduced activation region in ODD boys, while tal cortex when completing tasks of inhibitory and cognitive
the area in Fig. 5b, centered at (36, 22, 14) and (32, 28, 2), control (Silk et al. 2005; Pliszka et al. 2006; Rubia et al. 2005,
represents greater activation in ODD boys. Compared with the 2008). Unlike the findings of previous ADHD studies, only
same template, Fig. 5c depicts the location differences be- the part of rIFG in ODD boys showed significant under-
tween the areas in Fig. 5a and b. These results suggest that a activation during response inhibition in the current study.
portion of rIFG in ODD boys has a lower regional activity The higher activation in adjacent brain regions found in
level and poorer capacity for inhibition response, assuming ODD boys was probably recruited to make up some reduced
that IFC plays a major role in response inhibition. Meanwhile, activation in the rIFG; although this is speculative and requires
other brain regions, especially adjacent cortices such as dor- additional supporting evidence.
solateral parts of the bilateral inferior frontal gyrus and middle Compared to CD, disorder-specific abnormalities were re-
or superior frontal gyrus exhibited higher activation in ODD ported in boys with CD in the paralimbic system comprising
boys. According to Lis research results, the decreased activity 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 595

attention, inhibition and reward (Rubia et al. 2008, 2009a, b). Meanwhile, we collected fMRI data from 11 pure ODD boys
Rubia first found that the temporal and parietal brain regions are who were selected from thousands of boys with similar edu-
dysfunctional in CD and, furthermore, that these dysfunctions cation backgrounds. The difficulty in finding pure ODD boys
are specific to children with CD in the context of inhibitory resulted in a relatively small sample size, which is admittedly
control. However, this study did not find significant dysfunc- another limiting factor in this study.
tions in temporal or parietal areas as shown in previous CD During the selection of boys with pure ODD, we did not
literature. A reasonable explanation for this inconsistency is that further diagnose if any participant had attention problems (but
the current study investigated different psychiatric disorders, not reaching ADHD severity since ADHD is excluded). These
and dysfunctions in the parietal and temporal regions of ODD symptoms at the sub-clinical level can be related to neuropsy-
patients during inhibition response are not so pronounced as to chological deficits and need to be controlled dimensionally by
be observed. Therefore, this finding suggests that ODD might using ADHD and/or ODD symptoms as a covariate. Other-
be a less severe cognitive disorder compared to CD. wise, this could have helped us better clarify if ODD results in
The behavioral problems of children diagnosed with DBD reduced inhibitory control capability or simply an attention
but no comorbid disorder involving executive functioning problem, considering that there are currently two viewpoints
may be more strongly influenced by amilial/environmental regarding IFC function.
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 Conclusion
DBD in presence of ADHD teens underlines this possibility,
although the family stress of DBD in general (regardless of To our knowledge, this is the first fMRI study of pure ODD
ADHD comorbidity) also likely influences this result (both boys using a response inhibition task. We found that ODD
groups differ from controls) (Hummer et al. 2011). Poor participants showed significantly reduced activation in the
modeling by parents or other authority figures, negative or rIFG, but higher activation in adjacent areas such as dorsolat-
inconsistent discipline (Snyder et al. 1997), and social cogni- eral parts of the bilateral inferior frontal gyrus and middle or
tion impairments (Dodge 1993) may play a more significant superior frontal gyrus. We further inferred that ODD is a less
role in the etiology of DBDs, especially when ADHD is pronounced functional disorder compared to ADHD and CD.
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 References
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