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Deficient Activity in the Neural Systems That Mediate Self-regulatory Control in Bulimia Nervosa

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  • Silver Hill Hospital

Abstract and Figures

Disturbances in neural systems that mediate voluntary self-regulatory processes may contribute to bulimia nervosa (BN) by releasing feeding behaviors from regulatory control. To study the functional activity in neural circuits that subserve self-regulatory control in women with BN. We compared functional magnetic resonance imaging blood oxygenation level-dependent responses in patients with BN with healthy controls during performance of the Simon Spatial Incompatibility task. University research institute. Forty women: 20 patients with BN and 20 healthy control participants. Main Outcome Measure We used general linear modeling of Simon Spatial Incompatibility task-related activations to compare groups on their patterns of brain activation associated with the successful or unsuccessful engagement of self-regulatory control. Patients with BN responded more impulsively and made more errors on the task than did healthy controls; patients with the most severe symptoms made the most errors. During correct responding on incongruent trials, patients failed to activate frontostriatal circuits to the same degree as healthy controls in the left inferolateral prefrontal cortex (Brodmann area [BA] 45), bilateral inferior frontal gyrus (BA 44), lenticular and caudate nuclei, and anterior cingulate cortex (BA 24/32). Patients activated the dorsal anterior cingulate cortex (BA 32) more when making errors than when responding correctly. In contrast, healthy participants activated the anterior cingulate cortex more during correct than incorrect responses, and they activated the striatum more when responding incorrectly, likely reflecting an automatic response tendency that, in the absence of concomitant anterior cingulate cortex activity, produced incorrect responses. Self-regulatory processes are impaired in women with BN, likely because of their failure to engage frontostriatal circuits appropriately. These findings enhance our understanding of the pathogenesis of BN by pointing to functional abnormalities within a neural system that subserves self-regulatory control, which may contribute to binge eating and other impulsive behaviors in women with BN.
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ORIGINAL ARTICLE
Deficient Activity in the Neural Systems That
Mediate Self-regulatory Control in Bulimia Nervosa
Rachel Marsh, PhD; Joanna E. Steinglass, MD; Andrew J. Gerber, MD; Kara Graziano O’Leary, MA;
Zhishun Wang, PhD; David Murphy, MSci; B. Timothy Walsh, MD; Bradley S. Peterson, MD
Context:Disturbances in neural systems that mediate
voluntary self-regulatory processes may contribute to bu-
limia nervosa (BN) by releasing feeding behaviors from
regulatory control.
Objective:To study the functional activity in neural cir-
cuits that subserve self-regulatory control in women with
BN.
Design:We compared functional magnetic resonance
imaging blood oxygenation level–dependent responses
in patients with BN with healthy controls during perfor-
mance of the Simon Spatial Incompatibility task.
Setting:University research institute.
Participants:Forty women: 20 patients with BN and
20 healthy control participants.
Main Outcome Measure:We used general linear mod-
eling of Simon Spatial Incompatibility task–related acti-
vations to compare groups on their patterns of brain ac-
tivation associated with the successful or unsuccessful
engagement of self-regulatory control.
Results:Patients with BN responded more impulsively
and made more errors on the task than did healthy con-
trols; patients with the most severe symptoms made the
most errors. During correct responding on incongruent
trials, patients failed to activate frontostriatal circuits to
the same degree as healthy controls in the left inferolat-
eral prefrontal cortex (Brodmann area [BA] 45), bilat-
eral inferior frontal gyrus (BA 44), lenticular and cau-
date nuclei, and anterior cingulate cortex (BA 24/32).
Patients activated the dorsal anterior cingulate cortex (BA
32) more when making errors than when responding cor-
rectly. In contrast, healthy participants activated the an-
terior cingulate cortex more during correct than incor-
rect responses, and they activated the striatum more when
responding incorrectly, likely reflecting an automatic re-
sponse tendency that, in the absence of concomitant an-
terior cingulate cortex activity, produced incorrect
responses.
Conclusions:Self-regulatory processes are impaired in
women with BN, likely because of their failure to en-
gage frontostriatal circuits appropriately. These find-
ings enhance our understanding of the pathogenesis of
BN by pointing to functional abnormalities within a neu-
ral system that subserves self-regulatory control, which
may contribute to binge eating and other impulsive be-
haviors in women with BN.
Arch Gen Psychiatry. 2009;66(1):51-63
BULIMIA NERVOSA (BN) TYPI-
cally begins in adolescence or
young adulthood. Primarily
affecting girls and women, it
is characterized by recur-
rent episodes of binge eating followed by
self-induced vomiting or another compen-
satory behavior to avoid weight gain. These
episodes of binge eating are associated with
a severe sense of loss of control.1,2 Mood dis-
turbances and impulsive behaviors are com-
mon in individuals with BN, suggesting the
presence of more pervasive difficulties in be-
havioral self-regulation.2Thus, dysregu-
lated control systems may contribute to the
binge eating and associated purging behav-
iors, perhaps by releasing feeding behav-
iors from regulatory control. Concomitant
with familial and sociocultural determi-
nants,1disturbances in these systems likely
contribute to the pathogenesis of BN.
The functions of self-regulatory con-
trol rely on frontostriatal components of
cortico-striato-thalamo-cortical circuits, in-
cluding projections from the ventral pre-
frontal cortex (PFC) and anterior cingu-
late cortex (ACC) to the basal ganglia.3The
Simon Spatial Incompatibility task4en-
gages these functions by requiring partici-
pants to ignore a prepotent feature of a
stimulus to respond to a more task-
relevant one. Participants must indicate the
direction that an arrow is pointing (left or
right), regardless of the side of a screen on
Author Affiliations: Division of
Child and Adolescent
Psychiatry (Drs Marsh, Gerber,
Wang, and Peterson;
Ms Graziano O’Leary; and Mr
Murphy), and The Eating
Disorders Clinic (Drs Steinglass
and Walsh), Department of
Psychiatry, New York State
Psychiatric Institute and the
College of Physicians and
Surgeons, Columbia University,
New York, New York.
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which it appears. When the direction matches the side
of the screen on which the arrow appears, participants
perform the task easily, as demonstrated by their rapid
responses and infrequent errors. When the direction does
not match the side of the screen (eg, a leftward-pointing
arrow on the right side), the task is more difficult, as in-
dicated by slower responses and more errors. Ignoring
the task-irrelevant feature on these incongruent trials re-
quires the mobilization of attentional resources, resolu-
tion of cognitive conflict, inhibition of automatic re-
sponse tendencies, and thus the engagement of voluntary
self-regulatory control processes.
Healthy individuals activate large expanses of ACC, PFC,
and striatum while performing the Simon Spatial Incom-
patibility task5-7; this is consistent with findings from stud-
ies of healthy individuals performing other tasks requir-
ing conflict resolution and response inhibition (eg, Stroop,
go/no-go, flanker, and stop tasks).7-12 By comparing brain
activation during successful and unsuccessful trials, these
studies have additionally highlighted the differential con-
tributions of various prefrontal regions to self-regulatory
functions. Some findings suggest that the dorsal ACC pref-
erentially mediates performance or error monitoring,7-10
whereas others implicate the rostral ACC in affective re-
sponses to the commission of errors.13-15
Patients with BN perform worse than controls on vari-
ous executive function tasks.16-18 Findings of increased
interference from disorder-salient words (eg, food- and/or
body shape–related stimuli) on modified Stroop tasks19-24
suggest that poor inhibitory performance in patients with
BN reflects their attentional bias toward food, weight, and
body shape. However, patients with BN also tend to make
more inhibitory failures than controls on go/no-go tasks25
and show deficits in cognitive switching,26,27 which sug-
gests that they are cognitively impulsive26,28 and have more
generalized deficits in response inhibition and volun-
tary control processes. No functional magnetic reso-
nance imaging study to date has investigated these pro-
cesses in BN with a standard task of response inhibition.
We report on an event-related functional magnetic
resonance imaging study in which we used the Simon Spa-
tial Incompatibility task to investigate differences in the
neural substrates of self-regulatory control in women with
and without BN. Our a priori hypothesis was that pa-
tients with BN would not engage frontostriatal regula-
tory circuits to the same extent as healthy comparison
participants. Based on prior electrophysiological find-
ings of reduced error monitoring in patients with an-
orexia nervosa,29 we suspected that exploratory analy-
ses would reveal an altered pattern of error-related brain
activity in the ACC of patients relative to controls.
METHODS
PARTICIPANTS
Patients were recruited through the Eating Disorders Clinic at
the New York State Psychiatric Institute, where they were re-
ceiving treatment. Controls were recruited through flyers posted
in the local community. Patients and controls were women
matched by age and body mass index. Participants with a his-
tory of neurological illness, past seizures, head trauma with loss
of consciousness, mental retardation, pervasive developmen-
tal disorder, or current Axis I disorders (other than major de-
pression in the patients) were excluded. Controls had no life-
time Axis I disorders. The institutional review board at the New
York State Psychiatric Institute approved this study and all par-
ticipants gave informed consent before participating.
Formal diagnoses of BN were established through clinical
interviews conducted by a board-certified psychiatrist. The pres-
ence of comorbid neuropsychiatric diagnoses were estab-
lished using the Structured Clinical Interview for DSM Disor-
ders.30 Bulimic symptom severity and prior diagnoses of anorexia
nervosa were assessed using the Eating Disorders Examina-
tion.31 The Beck Depression Inventory II (BDI-II)32 and the
Hamilton Depression Scale33 quantified depressive symptoms.
The DuPaul-Barkley attention-deficit/hyperactivity disorder rat-
ing scale quantified symptoms of inattention and hyperactiv-
ity.34 Full-scale IQs were estimated using the Wechsler Abbre-
viated Scale of Intelligence.35
STIMULI
Stimuli were presented through nonmagnetic goggles (Resonance
Technology Inc, Northridge, California) using E-Prime software
(Psychology Software Tools Inc, Pittsburgh, Pennsylvania). A se-
ries of white arrows pointing either left or right were displayed against
a black background either to the left or right of a midline crosshair.
Stimuli subtended 1° vertical and 3.92° horizontal of the visual field.
Stimuli were either congruent (pointing in the same direction as
their position on the screen) or incongruent (pointing in the op-
posite direction of their position on the screen).
Participants were instructed to respond quickly to the di-
rection of the arrows by pressing a button on a response box
with their right hand, using their index finger for a left-
pointing arrow and their middle finger for a right-pointing ar-
row. The button-press recorded responses and reaction times
for each trial. Stimulus duration was 1300 milliseconds, with
an interstimulus interval of 350 milliseconds. Each run con-
tained 102 stimuli (185 seconds), with an incongruent stimu-
lus presented pseudorandomly every 13 to 16 congruent stimuli
(21.5-26.4 seconds apart). In each run, 51 arrows were left-
pointing and 51 were right-pointing; 51 appeared to the left of
the midline and 51 appeared to the right. Half of the incon-
gruent stimuli required the same response as the preceding con-
gruent stimulus. Each experiment contained 10 runs, totaling
68 incongruent and 952 congruent stimuli.
IMAGE ACQUISITION
The functional images were obtained using a T2*-sensitive, gra-
dient-recalled, single-shot, echo-planar pulse sequence (rep-
etition time=2200 milliseconds, echo time=30 milliseconds,
90° flip angle, single excitation per image, 2424-cm field of
view, 6464 matrix, 34 slices 3.5-mm thick, no gap, covering
the entire brain). We collected 80 echoplanar imaging vol-
umes for each run.
BEHAVIORAL ANALYSIS
Reaction times and accuracy scores were entered as depen-
dent variables in separate repeated-measure, linear mixed mod-
els in SAS, version 9.0 (SAS Institute Inc, Carey, North Caro-
lina) with diagnosis (BN or healthy control), age, full-scale IQ,
and BDI-II scores as covariates. Stimulus type (congruent or
incongruent) was the within-subject variable in each model.
Group differences in performance on congruent and incon-
gruent trials were tested by assessing the significance of the
diagnosisstimulus interaction in each model. We used an un-
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paired ttest to assess group differences in interference scores
(mean reaction times for incongruentmean reaction times for
congruent trials). Posterror adjustments in performance were
calculated for both groups.36,37 In patients, correlation analy-
ses assessed the association of behavioral performance with the
severity of symptoms.
IMAGE ANALYSIS
Preprocessing procedures are described in Supplemental Mate-
rial available at http://childpsych.columbia.edu/brainimaging
/supplementalmaterial/MarshR_0804.doc. First-level paramet-
ric analyses were conducted individually for each participant using
a modified version of the general linear model in statistical para-
metric mapping 2 (SPM2) (Wellcome Department of Imaging Neu-
roscience, London, England). Preprocessed blood oxygenation
level–dependent time series data at each voxel, concatenated from
all 10 runs of the Simon Spatial Incompatibility task (800 vol-
umes), were modeled using 3 independent functions for each run
(30 independent variables in total): (1) a boxcar function repre-
senting incongruent correct trials, convolved with a canonical he-
modynamic response function, (2) a boxcar function represent-
ing congruent correct trials, convolved with a hemodynamic
response function, and (3) a constant, following the principles
of SPM.38 Euclidean normalization and orthogonalization of para-
metric variables (SPM2 default functions) were not performed.
For each participant, least-squares regression estimated para-
meters for the 30 independent variables. These estimates for the
10 runs were summed to produce 2 contrast images per partici-
pant: (1) incongruent-correct vs congruent-correct, and (2) in-
congruent-incorrect vs incongruent-correct, which assessed brain
activity during engagement of self-regulatory control and the com-
mission of errors, respectively.
HYPOTHESIS TESTING
We tested whether patients and controls differed in brain ac-
tivity during correct responses on incongruent trials com-
pared with correct responses on congruent trials. An analysis
of covariance with interference scores as covariates identified
group differences in brain activity, independent of task perfor-
mance (Supplemental Material).
RESULTS
PARTICIPANTS
Twenty BN patients and 20 controls participated. All were
right-handed. Patients included 9 inpatients who under-
went testing within 1 month of admission and 8 outpa-
tients. The remaining 4 patients were no longer receiving
treatment but were still symptomatic. No one met criteria
for major depression or attention-deficit/hyperactivity dis-
order (Table 1). Six patients were taking selective sero-
tonin reuptake inhibitors. Groups did not differ in move-
ment during the scan (Supplemental Material).
BEHAVIORAL PERFORMANCE
There was a significant diagnosisstimulus type
interaction (F1,38= 4.67; P= .03) that derived from faster
reaction times in the patients during incongruent cor-
rect trials compared with controls (t38=2.33, P= .02;
mean [SD], 634[8.6] vs 664 [8.6] milliseconds). Inter-
Table 1. Demographic and Clinical Characteristics of Study Participants
Characteristic
Mean (SD)
t38
P
Value
Patients With Bulimia Nervosa
(n= 20)
Controls
(n= 20)
Age, y 25.7 (7.0) 26.35 (5.7) 0.32 .75
Height, cm 165.4 (8.9) 164.8 (4.8) −0.18 .85
Weight, kg 62.0 (5.8) 59.9 (5.8) −1.11 .27
Body mass indexa22.92 (2.3) 22.24 (2.2) −0.96 .34
Duration of illness, y 9 (7.2)
Education, y 15.52 (2.2) 16.4 (1.7) 1.36 .18
WASI IQ
Full-scale 111.9 (10.9) 118.55 (13.0) 1.68 .10
Verbal 112.5 (12.4) 121.15 (11.4) 2.28 .02
Performance 109.15 (10.9) 110.75 (13.5) 0.41 .68
EDE rating, mean (SD), range
OBEs in past 28 d 35.8 (30.7), 8-135
Vomiting episodes in past 28 d 65.25 (75.2), 2-28
Preoccupation with shape and weight 4.4 (2.0), 2-6
HAM-D score 12.05 (7.9) 1.05 (1.2) −6.09 .001
BDI-II score 17.35 (14.5) 1.55 (2.8) −4.75 .001
ADHD rating scores
Total current 14.21 (10.8) 5.6 (5.9) −3.09 .004
Inattention 8.36 (6.7) 2.95 (3.8) −3.09 .004
Hyperactivity 5.85 (5.3) 2.65 (2.4) −2.42 .02
Past AN, No. (%) 6 (30)
Taking medication, No. (%) 6 (30)
Subclinical bulimia nervosa, No. (%)b3 (15)
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; AN, anorexia nervosa; BDI-II, Beck Depression Inventory II; EDE, Eating Disorders Examination;
HAM-D, Hamilton Depression Scale; OBE, objective bulimic episode; WASI, Wechsler Abbreviated Scale of Intelligence.
aCalculated as weight in kilograms divided by height in meters squared.
bPatients who presented with subclinical bulimia nervosa, with no binge eating (n=2) or vomiting episodes (n =1) during the 28 days prior to participation.
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ference scores were significantly lower in patients
owing to their faster responses on incongruent trials;
they also made significantly more errors on incongru-
ent trials (Table 2). Accuracy on incongruent trials
decreased across runs in the patients, suggesting a
diminishing reserve for inhibitory control with time
(Figure 1). Full-scale IQ, BDI-II, and attention-
deficit/hyperactivity disorder rating scores did not
account for significant variance in reaction times or
Table 2. Group Differences on Performance Measures
Measure
Mean (SD)
t38
P
Value
Patients With
Bulimia
Nervosa Controls
Mean reaction
time, ms
Incongruent 634 (8.6) 664 (8.6) 2.57 .01
Congruent 462 (8.6) 480 (8.6) 1.49 .14
Interferencea172 (4.4) 185 (4.4) 2.08 .04
Errors
Incongruent, % 10.1 (0.7) 7.4 (0.7) −2.59 .01
Congruent, % 4.5 (0.7) 4.2 (0.7) −0.33 .75
Effectb5.5 (0.76) 3.2 (0.76) 2.18 .04
Posterror
adjustments, ms
−40.69 (59.3) −24.5 (79.1) 0.69 c.49
aInterference=mean reaction time for incongruent tasks −mean reaction
time for congruent tasks.
bError effect= errors for incongruent tasks− errors for congruent tasks.
ct18.
900
400
450
500
550
600
650
700
750
800
850
Mean Reaction Time, ms
Congruent stimuli
Healthy controls
Incongruent stimuli
Patients with bulimia nervosa
Congruent stimuli
Incongruent stimuli
100
75
80
85
90
95
1 2 3 4 5 6 7 8 9 10
Task Run
Mean Correct Responses, %
A
B
Figure 1. Mean latency (A) and accuracy (B) of responses on the Simon
Spatial Incompatibility task as a function of bulimia nervosa.
A B C
z
=
0
vACC
vACC
ILPFC
IFG
IFG
Lent
Lent
Lent
STG
STG
Put
Put
Thal
GH
z
=
2
z
=
4
z
=
16
z
=
30
z
=
32
z
=
44
P
<
.05 P
<
.05 P
<
.001P
<
.001
SMA
IFG
IFG
IFG
dACC
dACC
MTG
vACC
vACC
ILPFC
IFG
IFG
Lent
Lent
Lent
STG
STG
Put
Put
Thal
GH
SMA
IFG
IFG
IFG
dACC
dACC
MTG
Figure 2. Axial slices showing group average brain activations during correct
trials of the Simon Spatial Incompatibility task in healthy controls and patients
with bulimia nervosa. A, Groupstimulus (congruent vs incongruent) interac-
tions were detected in frontostriatal regions (red). Main effects of stimulus con-
dition (congruent vs incongruent) are shown for the healthy participants (B) and
those with bulimia nervosa (C) (P.05, cluster 25 adjacent voxels; yielding a
conjoint effective, P.00000539). The combined application of a statistical
threshold and cluster filter substantially reduces the false-positive identification
of activated pixels at any given threshold.40 Increases in signal during correct
incongruent trials relative to correct congruent trials are shown in red, and de-
creases are shown in blue. dACC indicates dorsal anterior cingulate cortex;
GH, hippocampal gyrus; IFG, inferior frontal gyrus; ILPFC, inferolateral prefrontal
cortex; Lent, lenticular nucleus; MTG, medial temporal gyrus; Put, putamen;
SMA, supplementary motor area; STG, superior temporal gyrus; Thal, thalamus;
vACC, ventral anterior cingulate cortex.
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accuracy (P.1). Neither group exhibited posterror
slowing; to the contrary, patients responded signifi-
cantly faster on trials following incorrect (vs correct)
responses to incongruent stimuli (BN, mean, −40.7
[SD, 79] milliseconds, paired t18=−2.91, P= .01). Sig-
nificant inverse associations of accuracy scores on
incongruent trials with Eating Disorders Examination
scores (objective bulimic episodes: r=−0.21, P.001;
vomiting episodes: r=−0.26; P.001; preoccupation
with weight and body shape ratings: r=−0.09, P=.003)
indicated that the most symptomatic patients made
the most errors on trials that required volitional con-
trol. These inverse associations remained significant
even when covarying for depression severity and when
4 patients with BDI-II scores greater than 29 were
removed from the analyses.
A PRIORI HYPOTHESIS TESTING OF NEURAL
ACTIVITY DURING CORRECT RESPONSES
Correct responding on incongruent trials was associ-
ated with greater activation of frontostriatal regions in
controls than in patients (Figure 2 and Table 3), in-
cluding the left inferolateral PFC (Brodmann area [BA]
45, P=.004) and left lenticular nucleus (P=.008). On the
right side, these regions included the ventral and dorsal
ACC (BA 24/32, P=.01), putamen (P=.01), and caudate
nucleus (P=.001). Increased activation in controls was
detected bilaterally in the inferior frontal gyrus (BA 44,
P=.005) and thalamus (P=.01).
EXPLORATORY ANALYSES
Interference Correlates
Significant interactions of diagnosis with interference
scores during correct responses to conflict trials were de-
tected in prefrontal cortices (inferolateral PFC, inferior
frontal gyrus, and dorsolateral PFC) and the dorsal stria-
tum (Figure 3C) deriving from stronger correlations in
the patients, in whom higher interference scores accom-
panied greater activation of the dorsolateral PFC and pa-
rietal cortices (Figure 3B). In contrast, greater subcorti-
cal activation (dorsal striatum, lenticular nucleus, and
thalamus) and less activation of the ventral ACC and the
superior temporal and posterior cingulate cortices ac-
companied greater interference scores in controls
(Figure 3A).
Neural Activity During the Commission of Errors
Activity in subcortical brain areas during the commis-
sion of errors relative to correct responses on conflict
trials was greater in controls than in patients, particu-
larly in the right caudate (P=.01) and right lenticular
nucleus (P=.01), and less in the dorsal ACC (BA 24/32)
and dorsolateral PFC (BA 9/46) (Figure 4 and
Table 4). These findings suggest a differential role of
subcortical and cortical regions in task performance in
controls, with greater subcortical activity accompanying
errors and greater dorsal ACC and dorsolateral PFC
activity accompanying correct responses. In contrast,
slightly greater dorsal ACC activity was detected in
patients during errors than during correct responses
(BA 24/32, P=.006) (Figure 4C), suggesting that the
neural origin of errors and the response to them likely
differs between BN patients and controls.
Correlations of activation during correct responses to
conflict stimuli with the number of errors committed
throughout the task support this interpretation. More er-
rors were committed by the controls who activated sub-
cortical regions (ventral striatum and lenticular nucleus)
and the inferior supplementary motor area the most
(Figure 5A). In contrast, patients who made the most
errors generated the least activation of the PFC (ventral
ACC and inferior frontal gyrus), insula, ventral stria-
tum, and supplementary motor area (Figure 5B). These
group differences produced diagnosiserror interac-
tions in frontostriatal regions (Figure 5C). Moreover, cor-
relations of posterror adjustment scores with activation
during errors indicated that less dorsal ACC activation
during errors (relative to correct responses) accompa-
nied greater posterror slowing in controls (Figure 5D).
Time course analyses revealed that dorsal ACC activa-
tions following correct and incorrect responses were pro-
longed in controls compared with activations in pa-
tients, rising earlier and declining later (Figure 6).
Table 3. Greater Frontostriatal Activations in Controls Compared With Patients With Bulimia Nervosa During the Engagement
of Self-regulatory Control
Activated Region
Location
No. of
Voxels
Peak Location
t
Statistic
P
ValueSide BA x y z
Inferolateral prefrontal cortex L 45 112 −40 42 −6 2.55 .004
Lenticular nucleus L NA 917 −22 −4 −2 2.77 .008
Inferior frontal gyrus L 44 448 −52 −6 −4 2.55 .007
R 44 322 48 2 −6 2.68 .005
Thalamus L/R NA 55 24 −26 −2 2.39 .01
Anterior cingulate cortex R 32 205 12 36 32 2.40 .01
R 32 33 12 50 0 2.34 .01
Putamen R NA 151 22 −6 0 2.16 .01
Caudate nucleus R NA 32 20 6 16 2.14 .01
Abbreviations: BA, Brodmann area; L, left; NA, not applicable; R, right.
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Correlations With Symptom Severity
The number of objective bulimic episodes in the patient
group correlated inversely with activation of the right me-
dial prefrontal (P=.005), temporal (P=.003), and inferior
parietal (P= .001) cortices and the caudate nucleus (P=.005)
(Figure 7A), indicating reduced frontostriatal activation
in those with the most severe symptoms. In addition, their
ratings of preoccupation with body shape and weight cor-
related inversely with activation of the left caudate (P=.03)
and left insula (P=.03), indicating that the most preoccu-
pied patients engaged these areas the least (Figure 7B).
Medication, IQ, and Comorbidity Effects
Comparing the group average activation map of only the
patients who were not taking medications with a map of
all patients suggested that medication did not contrib-
ute to our findings. Likewise, a history of anorexia ner-
vosa, depressive or attention-deficit/hyperactivity disor-
der symptoms, and IQ scores were not associated with
A B C
z
=
0
Interference correlates
z
=
2
z
=
4
z
=
16
z
=
30
z
=
32
P
<
.05 P
<
.05 P
<
.001P
<
.001
ILPFC
IFG
IFG
Cd
DLPFC
DLPFC
ILPFC
IFG
IFG
Cd
DLPFC
DLPFC
Figure 3. Correlations of mean reaction times with signal change during
correct conflict trials of the Simon Spatial Incompatibility task in healthy
controls (A) and patients with bulimia nervosa (B). Positive correlations are
in red, and inverse correlations are in blue. C, Diagnosis interference
interactions in prefrontal regions and the caudate nucleus (Cd) stemming
from the interference correlates in the patients (P.05, cluster 25
adjacent voxels). DLPFC indicates dorsolateral prefrontal cortex; IFG, inferior
frontal gyrus; and ILPFC, inferolateral prefrontal cortex.
A B C
z
=
2
z
=
4
z
=
6
z
=
16
z
=
8
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=
20
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=
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=
34
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<
.05 P
<
.05 P
<
.001P
<
.001
Cd
Cd
Lent
Lent
ACC
ACC
ACC
ACC
DLPFC
Cd
Cd
Lent
Lent
ACC
ACC
dACC
dACC
DLPFC
Figure 4. Group average brain activity during the commission of errors.
A, Groupresponse (incorrect vs correct) interactions were detected in
frontostriatal brain areas (P.05, cluster 25 adjacent voxels). Functional
magnetic resonance imaging signal associated with incorrect vs correct
responding on incongruent trials of the Simon Spatial Incompatibility task
was greater in controls compared with patients with bulimia nervosa in the
striatum (red). Increased activity in patients with bulimia nervosa was most
prominent in the anterior cingulate cortex (ACC) (blue). Main effects of
response are shown in the controls (B) and patients with bulimia nervosa
(C). Increases in signal during incorrect incongruent trials relative to
incorrect congruent trials are shown in red, and decreases are shown in blue.
Cd indicates caudate nucleus; dACC, dorsal ACC; DLPFC, dorsolateral
prefrontal cortex; and Lent, lenticular nucleus.
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group differences in brain activations (Figure 8 and
Supplemental Material).
COMMENT
Patients with BN exhibited greater impulsivity than did
control participants, responding faster and making more
errors on conflict trials that required self-regulatory con-
trol to respond correctly. They responded faster on con-
gruent trials following incorrect conflict trials, suggest-
ing impulsive responding even immediately after having
committed an error. Even when they responded cor-
rectly on conflict trials, the patients did not generate the
same magnitude of neural activity as controls in the fron-
tostriatal pathways that subserve self-regulatory con-
trol, including the left inferolateral PFC (BA 45), len-
ticular nucleus, inferior frontal gyrus (bilaterally) (BA 44),
dorsal ACC (BA 24/32), putamen, and caudate. The less
they activated these circuits, the faster they responded
to conflict trials. Moreover, patients who generated less
activation of frontostriatal circuits (ACC, inferior fron-
tal gyrus, insula, and caudate) also committed more er-
rors across all trials, whereas controls committed more
errors when generating greater activity in the striatum.
Likewise, when erring on conflict trials, controls dis-
played more activity in subcortical portions of fronto-
striatal circuits (left putamen, right caudate, and right len-
ticular nuclei) and less activation of the dorsal ACC,
suggesting that their overreliance on subcortical nuclei
in the absence of dorsal ACC activity was associated with
more errors. In addition, greater dorsal ACC activity dur-
ing correct compared with incorrect conflict trials ac-
companied more posterror slowing in the controls, likely
reflecting enhanced conflict monitoring relative to pa-
tients.10,41-43 In contrast, patients generated slightly more
activity in the dorsal ACC when making errors than when
responding correctly on conflict trials, suggesting en-
hanced error detection in the patients but limited suc-
cess in monitoring performance and correcting er-
rors.41,44,45 Finally, the patients who generated less activity
in frontostriatal circuits were those most severely af-
fected with bulimic symptoms.
These group differences in performance and patterns
of brain activity suggest that individuals with BN do not
activate frontostriatal circuits appropriately, perhaps con-
tributing to impulsive responses to conflict stimuli that
normally require both frontostriatal activation and the
exercise of self-regulatory control to generate a correct
response. We speculate that this inability to engage fron-
tostriatal systems also contributes to their inability to regu-
late binge-type eating and other impulsive behaviors.
IMPAIRED BEHAVIORAL PERFORMANCE
Impulsive responding in women with BN suggests the
presence of an impaired ability to regulate responses to
conflict stimuli, which is consistent with their impulsiv-
ity during binge eating while they struggle with conflict-
ing desires to consume fattening foods and avoid weight
gain. Our behavioral findings are consistent with those
of impaired performance on a go/no-go task in patients
with BN25 and with hypothesized links of binge-eating
behaviors to behavioral impulsivity.46,47 Moreover, accu-
racy on the Simon Spatial Incompatibility task corre-
lated inversely with BN symptom severity, indicating that
those with the most severe symptoms were proportion-
ately less able to inhibit incorrect responses on incon-
gruent trials. Thus, patients with BN may have a more
generalized difficulty regulating thought and behavior in
domains other than feeding.
DEFICIENT ACTIVITY IN NEURAL SYSTEMS
THAT SUBSERVE SELF-REGULATORY CONTROL
Patients did not generate the same magnitude of activa-
tion in frontostriatal circuits as controls during correct
responses on conflict trials. Previous functional mag-
netic resonance imaging studies reported prominent fron-
tostriatal activity in healthy individuals during Simon con-
flict trials, particularly in the ACC, supplementary motor
area, middle and inferior frontal cortex, dorsolateral PFC,
caudate, and putamen.5-7,37 Similar paradigms that mea-
sure the ability to inhibit cognitive interference or pre-
potent responses also generate frontostriatal activity in
healthy individuals.8,11,12,48,49
Although controls activated both frontal and striatal
regions more with increasing interference, patients pri-
marily activated the dorsolateral PFC and parietal cor-
tex more with increasing interference (Figure 3). These
findings suggest that increasing activity of frontostriatal
circuits in the Simon task supports the regulation of be-
havior in the presence of conflicting response tenden-
Table 4. Error-Related Activations in Patients With Bulimia Nervosa and Controls
Activated Region
Location
No. of
Voxels
Peak Location
t
Statistic
P
ValueSide BA x y z
More activation in controls than patients
Putamen L NA 249 −12 0 −8 2.45 .009
Caudate nucleus R NA 151 24 18 −2 2.45 .01
Lenticular nucleus R NA 53 8 12 10 2.21 .01
More activation in patients than in controls
Anterior cingulate cortex L/R 32 1859 −4 44 18 2.62 .006
Dorsolateral prefrontal cortex R 9/46 198 42 26 22 2.44 .01
Inferior frontal gyrus R 47 235 40 10 −12 2.51 .008
Abbreviations: BA, Brodmann area; L, left; NA, not applicable; R, right.
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cies. Increasing deficiencies in activating these circuits
in patients accompanied proportionately faster (more im-
pulsive) responses during conflict trials.
Our findings of deficient frontostriatal circuits are con-
sistent with a previous report of decreased activation of the
lateral PFC in response to food stimuli in patients with BN
compared with anorexia nervosa patients and controls50 who
were instructed to focus on feelings elicited by food vs non-
food stimuli. Because the lateral PFC is thought to contrib-
ute to the suppression of undesirable behaviors,51 diminished
activity in this region may account for the impulsivity and
loss of control in BN patients when eating.
ERROR-RELATED ACTIVITY
Analyses of brain activity during the commission of errors
relative to activity when responding correctly to conflict
stimuli further suggested that frontostriatal systems may
function abnormally in patients with BN. Controls acti-
vated the dorsal ACC more during correct than during in-
correct responses to conflict stimuli (Figure 4B). Further-
more, greater dorsal ACC activation during correct vs
incorrect responses accompanied more posterror slowing
(Figure 5D), likely reflecting a role for dorsal ACC activa-
tion in supporting correct responses to conflict trials
(Figure 4B) and in adjusting performance to ensure a cor-
rect response following an error.
Patients with BN, in contrast, activated the dorsal ACC
slightly more during incorrect than correct responses to
conflict trials (Figure 4C); its activation did not modu-
late their performance on subsequent trials (Figure 5E).
These findings may suggest the presence of heightened
error detection, but limited attempts at error correction,
in patients with BN, as their reaction times did not slow
following errors. In contrast, an electrophysiological study
of persons with anorexia nervosa reported lower error
A B C D E F
z
=
0
z
=
12
z
=
24
z
=
36
z
=
6
z
=
18
z
=
30
z
=
42
P
<
.05 P
<
.05 P
<
.001P
<
.001
Cd
Cd
Lent
Lent
Ins IFG
IFG
DLPFC
DLPFC
dACC
SMA
SMA
IFG
dACC
dACC
IFG
Ins
vACC
Cd
Cd
Lent
Lent
Ins IFG
IFG
DLPFC
DLPFC
dACC
SMA
SMA
IFG
dACC
IFG
Ins
vACC
Figure 5. Correlations of activations during correct trials with the total number of errors made on the Simon Spatial Incompatibility task by healthy controls (A)
and patients with bulimia nervosa (B). Positive correlations are shown in red, and inverse correlations are shown in blue. C, Diagnosiserror interactions were
detected in prefrontal and striatal regions. Correlations of activations during the commission of errors with posterror adjustment scores in the controls (D) and
patients with bulimia nervosa (E). These scores were calculated as the difference of the mean reaction times on trials immediately following erroneous responses
and the mean reaction times on trials immediately following correct responses (these subsequent trials were always congruent stimuli because incongruent trials
were never preceded by incongruent trials in our version of the Simon task). F, Diagnosisposterror interactions in the dorsal anterior cingulate cortex (dACC)
indicate that the controls who engaged this area the most during correct responses to conflict stimuli were those who slowed down most following correct conflict
trials (all, P.05, cluster 25 adjacent voxels). Cd indicates caudate nucleus; DLPFC, dorsolateral prefrontal cortex; IFG, inferior frontal gyrus; Ins, insula;
Lent, lenticular nucleus; SMA, supplementary motor area; and vACC, ventral anterior cingulate cortex.
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rates than in controls on a flanker task and reduced error-
related negativity, suggesting deficient error detec-
tion.29 Differences across patients with anorexia ner-
vosa and BN in their ability to detect errors, however,
may reflect their respective personality characteristics of
perfectionism and impulsiveness that distinguish pa-
tients with restricting-type from those with binge-type
eating disorders.52 Moreover, less activation of the dor-
sal ACC and prefrontal and parietal cortices accompa-
nied more errors in patients (Figure 5B), indicating that
deficient activation in these regions during correct re-
sponses (Figure 2C) was associated with less interfer-
ence (Figure 3B) and the commission of more errors in
patients (Figure 5B). Deficient cortical activation in the
patients thus likely accounted for their more impulsive,
error-prone performances compared with controls
(Figure 1). The differential role of dorsal ACC activity
in correct and incorrect responding in controls is con-
sistent with evidence that this area of the brain activates
during both error11 and conflict10 responses and may have
more than a single unitary function in healthy individuals.
Controls activated the striatum without activating cor-
tical regions during incorrect but not during correct re-
sponses (Figure 4B). The more they activated the stria-
tum, even during correct responses, the more errors they
made (Figure 5A). Thus, when generating more striatal
activity, controls were likely engaging an automatic re-
sponse tendency based within that region.53,54 In con-
trast, the more the patients activated both cortical and
subcortical regions (ie, the less deficient their overall pat-
tern of brain activation) (Figure 2), the fewer errors they
made. Deficient striatal activity in the patients seemed
simply to represent a deficient overall frontostriatal ac-
tivation that likely contributed to impulsive, erroneous
responses (Figure 4C).
Although the patients reported more depressive symp-
toms than did controls, covarying for depressive symp-
toms did not affect our findings. In addition, the dorsal
ACC activated in patients during the commission of er-
rors, whereas the rostral ACC has been shown to acti-
vate during affective responses to errors and has been im-
plicated in the pathogenesis of depression.15
0.5
0.2
0.1
0.0
0.1
0.2
0.3
0.4
BOLD Signal Intensity, %
0.5
0.2
0.1
0.0
0.1
0.2
0.3
0.4
0 5 10 15 20 25
Time After Stimulus, s
Patients With Bulimia Nervosa
Controls
BOLD Signal Intensity, %
Response to incongruent stimulus
Correct Incorrect
Figure 6. Temporal patterns of maximum dorsal anterior cingulate cortex
(x= −4, y= 34, z=26) activations following correct and incorrect responses to
incongruent stimuli in healthy controls and patients with bulimia nervosa
(extracted from Figure 3). Time courses were averaged across voxels in each
region of interest for both groups. BOLD indicates blood oxygenation
level–dependent.
A B
z
=
16
z
=
6
z
=
4
z
=
14 z
=
4
z
=
12 z
=
6
P
<
.05 P
<
.05
P
<
.001 P
<
.001
TC
Cd
IPC
IPC
Ins
Cd
Cd
TC
Cd
IPC
IPC
Ins
Ins
Ins
Cd
Cd
Figure 7. Main effects of symptom severity in patients with bulimia nervosa.
A, Inverse correlations of the number of objective bulimic episodes (from the
Eating Disorders Examination) with the magnitude of activation during
correct responding suggest that the patients with the most episodes of binge
eating and purging engaged cortical areas (medial prefrontal cortex,
temporal cortex [TC], and inferior parietal cortex [IPC]) and the head of the
caudate the least. B, Inverse associations of ratings of preoccupation with
weight and shape with task-related activations indicated that the most
preoccupied patients engaged the caudate and insula (Ins) the least (all,
P.05, cluster 25 adjacent voxels). Cd indicates caudate nucleus.
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TIME COURSE OF ACTIVATION
The time course of the blood oxygenation level–
dependent response in the dorsal ACC during processing
of incongruent stimuli differed in patients and controls
(Figure 6). Activation in controls following both correct
and incorrect responses rose earlier and declined later than
in patients. Peak activity also occurred earlier in controls.
Given that patients made more errors that increased across
runs (Figure 1), the association of more errors with less
dorsal ACC activity (Figure 5) suggests that the reduced
duration of the blood oxygenation level–dependent re-
sponse in patients likely contributed to their reduced ac-
tivation of this region during correct responses on con-
flict trials (Figure 2), thereby contributing to their impulsive,
erroneous responses. Reduced dorsal ACC activation in con-
trols during incorrect responses (Figure 4 and Figure 5)
suggests that the dorsal ACC mediates resolution of cog-
nitive conflict induced by incongruent stimuli, presum-
ably through the exertion of top-down control over auto-
matic response tendencies. In controls, these automatic
response tendencies were likely represented by increased
activity in the lenticular nucleus during the commission
of errors (Figure 4 and Figure 5). Thus, the shorter dura-
tion of dorsal ACC activity in patients may have contrib-
uted to their poorer performance throughout the task,
whereas failure to generate sufficient amplitude of the re-
sponse in this region contributed to erroneous responses
in the controls. Both groups generated activations that de-
clined more slowly following incorrect responses than fol-
lowing correct ones (Figure 6), suggesting the invocation
of either compensatory strategies or error-monitoring ac-
tivities in both groups. Posterror adjustments in perfor-
mance, however, were not associated with dorsal ACC ac-
tivity in patients (Figure 5E), which may indicate that this
compensatory strategy or error-monitoring activity failed
to reduce their errors on subsequent trials.
STRIATAL AND ANTERIOR
CINGULATE ACTIVATION
An excessive reliance on automatic responding, per-
haps in the service of responding quickly, would pro-
duce incorrect responses on incongruent trials. Indeed,
self-regulatory control is required to overcome auto-
matic and habitual responses, such as the stimulus-
response mappings that are acquired during the more fre-
quent congruent trials. The dorsal striatum mediates the
gradual acquisition of stimulus-response associations, vari-
ously termed procedural or habit-based learning.53 Top-
down control from the PFC via projections to the stria-
tum is required to modulate processing in these areas and
to produce a desired action.44,55 Thus, in controls, incor-
rect responding on incongruent trials was associated with
increased striatal activity, whereas correct responding on
these trials (the desired action) engaged both prefrontal
and striatal regions. A proper balance of cortical and sub-
cortical activity is likely required to respond correctly and
rapidly to incongruent stimuli.
Multiple functions have been assigned to roles that the
ACC plays in self-regulation.10,43,56 Some functional mag-
netic resonance imaging studies indicate that healthy par-
A B
z
=
0z
=
2
z
=
2z
=
4
z
=
4z
=
6
z
=
16 z
=
8
z
=
30 z
=
16
z
=
32 z
=
20
z
=
44 z
=
34
P
<
.05 P
<
.05 P
<
.001P
<
.001
ILPFC
ILPFC
Lent
Lent
dACC dACC
dACC
ILPFC
ILPFC
Lent
Lent
dACC
SMA
dACC
dACC
SMA
Figure 8. Group differences in brain activations accounting for comorbid
depression in patients with bulimia nervosa. A, Groupstimulus (congruent
vs incongruent) interactions were detected in frontostriatal regions (red).
Activations were still greater in healthy controls than in patients with bulimia
nervosa when we accounted for Beck Depression Inventory II scores.
B, Groupresponse (incorrect vs correct) interactions also remained the
same when we accounted for Beck Depression Inventory II scores (P.05,
cluster 25 adjacent voxels). dACC indicates dorsal anterior cingulate
cortex; ILPFC, inferolateral prefrontal cortex; Lent, lenticular nucleus; and
SMA, supplementary motor area.
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ticipants activate the rostral ACC during incorrect re-
sponses on the go/no-go9,13 and stop8tasks, suggesting
that this portion of the ACC preferentially monitors re-
sponse errors. A conflict-monitoring theory maintains that
ACC function enhances cognitive control during the pro-
cessing of conflicting stimuli, thereby reducing conflict
on subsequent trials.10,41-43 For example, conflict moni-
toring of the dorsal ACC on a Simon task predicted ad-
justments in reaction times to incongruent stimuli in
healthy participants.37 Another study of healthy indi-
viduals reported significantly less dorsal ACC activity for
incorrect than for correct incongruent trials on a Stroop
task,41 consistent with our findings. Thus, dorsal ACC
engagement likely helps healthy individuals override con-
flict to respond correctly on both tasks. Discrepant find-
ings regarding the roles of the ACC and other prefrontal
regions may reflect differences in the control processes
that are elicited by different tasks.57 Failing to distin-
guish the conflict-mediating and error-processing func-
tions of the dorsal ACC from the performance-
monitoring functions of the rostral ACC may have added
to the discrepant findings.14,58
ASSOCIATIONS WITH SYMPTOM SEVERITY
The number of objective bulimic episodes correlated
inversely with activation of the left caudate nucleus
and temporal and inferior parietal cortices, indicating
that the most symptomatic patients engaged these
regions the least, suggesting the presence of a dose-
dependence in the association of cortical-subcortical
activation with symptom severity. The most sympto-
matic patients also performed the worst on the task,
further suggesting that disturbances in self-regulatory
control in individuals with BN may be a consequence
of their reduced engagement of frontostriatal systems.
Patient ratings of their preoccupation with shape and
weight also correlated inversely with activations in the
left caudate nucleus and left insula, indicating that the
most preoccupied patients engaged these brain areas
the least, consistent with evidence showing that the
insula-opercular region is involved in the resolution of
cognitive interference.57
POSSIBLE MECHANISMS UNDERLYING
DEFICIENT SELF-REGULATORY CONTROL
The causes of the impulsive, erroneous responding and
deficient frontostriatal activation in women with BN dur-
ing performance of the Simon task are unknown. We
speculate that these deficits may be caused by previ-
ously reported decreases in serotonin metabolism in fron-
tal cortices in persons with BN.59,60 Altered serotonergic
function likely contributes to their disturbances in self-
regulatory control and mood.59,61 Even in healthy indi-
viduals, transient decreases in serotonergic neurotrans-
mission (induced through the acute depletion of dietary
tryptophan) produce impulsive and aggressive behav-
iors62 and reduces inferior PFC activity during tasks that
require inhibitory control.63 Thus, the impulsive respond-
ing and reduced prefrontal activation in our patients, with
prior reports of abnormalities in various serotonin indi-
ces in BN, suggests that altered serotonergic neurotrans-
mission likely decreased frontostriatal activation and im-
paired self-regulatory control. In addition, reduced
serotonin transporter availability in the thalami of per-
sons with BN61 is consistent with our finding of reduced
activation in thalamic portions of frontostriatal circuits.
The thalamus plays a crucial intermediary role in trans-
mitting information through frontostriatal circuits,64 which
suggests that abnormal serotonin transmission in tha-
lamic nuclei contributes to the overall dysfunction of fron-
tostriatal circuits in individuals with BN. Also notewor-
thy, frontostriatal regions depend heavily on dopaminergic
transmission for proper functioning.65 Failure to suffi-
ciently activate frontostriatal regions in patients there-
fore argues prima facie for the future study of dopamin-
ergic systems in BN.
CONCLUSIONS
The few extant neuroimaging studies in persons with BN
have investigated brain function at rest under con-
trolled conditions using body shape– or food-related
stimuli to elicit symptom-related processes in the brain.50,66
We instead used a task to assess the functioning of self-
regulatory control processes in individuals with BN in
the absence of disorder-specific stimuli. A limitation of
this study was the absence of a control group consisting
of impulsive individuals with healthy weights and eat-
ing behaviors, which would permit assessment of the
specificity of frontostriatal abnormalities in persons with
BN. In addition, we did not account for menstrual sta-
tus, which can affect neural functioning in women.67 We
have no reason to suspect, however, that menstrual sta-
tus differed systematically across groups to confound our
findings. Our inclusion of only adult women makes im-
possible the generalization of findings to men or adoles-
cents with BN. Moreover, impaired self-regulatory con-
trol could be a consequence of chronic illness in the
patients. Thus, future studies should evaluate the func-
tioning of frontostriatal systems in adolescents with BN
closer to the onset of illness. Our sample was heteroge-
neous in symptom severity, and patients were at differ-
ing stages of treatment. Thus, future studies should in-
clude larger samples of patients with eating disorders.
Studying patients after the remission of symptoms would
provide insight into whether impairments in self-
regulation are trait- or state-related.
Submitted for Publication: December 3, 2007; final re-
vision received June 13, 2008; accepted June 18, 2008.
Correspondence: Rachel Marsh, PhD, Columbia Uni-
versity and the New York State Psychiatric Institute, 1051
Riverside Dr, Unit 74, New York, NY 10032 (marshr
@childpsych.columbia.edu).
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by
grants K02-74677 and K01-MH077652 from the Na-
tional Institute of Mental Health, by a grant from the Na-
tional Alliance for Research on Schizophrenia and De-
pression, and by funding from the Sackler Institute for
Developmental Psychobiology, Columbia University.
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61
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Additional Information: Supplemental material is avail-
able at http://childpsych.columbia.edu/brainimaging
/supplementalmaterial/MarshR_0804.doc.
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Correction
Error in Funding/Support. In the Original Article by
Strigo et al titled “Association of Major Depressive Dis-
order With Altered Functional Brain Response During
Anticipation and Processing of Heat Pain,” published in
the November issue of the Archives (2008;65[11]:1275-
1284), there was an error in the Funding/Support sec-
tion. It should have said that Drs Paulus and Simmons
were supported by the University of California San Diego
Center of Excellence for Stress and Mental Health, not
Drs Paulus and Strigo.
(REPRINTED) ARCH GEN PSYCHIATRY/ VOL 66 (NO. 1), JAN 2009 WWW.ARCHGENPSYCHIATRY.COM
63
©2009 American Medical Association. All rights reserved.
at Columbia University, on January 6, 2009 www.archgenpsychiatry.comDownloaded from
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Article
An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.
Article
Obtained data from parents and teachers for a large sample of urban school children aged 6 to 12 years on the attention deficit hyperactivity disorder (ADHD) Rating Scale, and collected criterion measures (e.g., direct observations of classroom behavior, academic achievement scores) on a smaller subsample. The ADHD Rating Scale was found to be a highly reliable questionnaire with adequate criterion-related validity. Strong differences between boys and girls were evident with respect to the frequency of ADHD symptomatology. The ADHD Rating Scale should be useful as one component of a multimodal assessment approach that would include rating scales surveying both general and specific areas of psychopathology.
Article
The specific psychopathology of anorexia nervosa and bulimia nervosa is complex in form. Although for many purposes self-report questionnaires are a satisfactory measure of this psychopathology, for detailed psychopathological studies and for investigations into the effects of treatment, more sensitive and flexible assessment measures are required. For this reason a semi-structured interview was developed. This interview, the Eating Disorder Examination, is designed to assess the full range of the specific psychopathology of eating disorders, including these patients' extreme concerns about their shape and weight.
Article
The Stroop and Simon tasks typify a class of interference effects in which the introduction of task-irrelevant stimulus characteristics robustly slows reaction times. Behavioral studies have not succeeded in determining whether the neural basis for the resolution of these interference effects during successful task performance is similar or different across tasks. Event-related functional magnetic resonance imaging (fMRI) studies were obtained in 10 healthy young adults during performance of the Stroop and Simon tasks. Activation during the Stroop task replicated findings from two earlier fMRI studies. These activations were remarkably similar to those observed during the Simon task, and included anterior cingulate, supplementary motor, visual association, inferior temporal, inferior parietal, inferior frontal, and dorsolateral prefrontal cortices, as well as the caudate nuclei. The time courses of activation were also similar across tasks. Resolution of interference effects in the Simon and Stroop tasks engage similar brain regions, and with a similar time course. Therefore, despite the widely differing stimulus characteristics employed by these tasks, the neural systems that subserve successful task performance are likely to be similar as well. © 2002 Elsevier Science B.V. All rights reserved.
Chapter
This authoritative handbook reviews the breadth of current knowledge on the conscious and nonconscious processes by which people regulate their thoughts, ...
Article
The typical functional magnetic resonance (fMRI) study presents a formidable problem of multiple statistical comparisons (i.e, > 10,000 in a 128 x 128 image). To protect against false positives, investigators have typically relied on decreasing the per pixel false positive probability. This approach incurs an inevitable loss of power to detect statistically significant activity. An alternative approach, which relies on the assumption that areas of true neural activity will tend to stimulate signal changes over contiguous pixels, is presented. If one knows the probability distribution of such cluster sizes as a function of per pixel false positive probability, one can use cluster-size thresholds independently to reject false positives. Both Monte Carlo simulations and fMRI studies of human subjects have been used to verify that this approach can improve statistical power by as much as fivefold over techniques that rely solely on adjusting per pixel false positive probabilities.
Article
Current approaches to detecting significantly activated regions of cerebral tissue use statistical parametric maps, which are thresholded to render the probability of one or more activated regions of one voxel, or larger, suitably small (e. g., 0.05). We present an approximate analysis giving the probability that one or more activated regions of a specified volume, or larger, could have occurred by chance. These results mean that detecting significant activations no longer depends on a fixed (and high) threshold, but can be effected at any (lower) threshold, in terms of the spatial extent of the activated region. The substantial improvement in sensitivity that ensues is illustrated using a power analysis and a simulated phantom activation study. © 1994 Wiley-Liss, Inc.