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Articles   |    
Neural Mechanisms of Frustration in Chronically Irritable Children
Christen M. Deveney, Ph.D.; Megan E. Connolly, B.A.; Catherine T. Haring, B.A.; Brian L. Bones, B.A.; Richard C. Reynolds, M.S.; Pilyoung Kim, Ph.D.; Daniel S. Pine, M.D.; Ellen Leibenluft, M.D.
Am J Psychiatry 2013;170:1186-1194. doi:10.1176/appi.ajp.2013.12070917
View Author and Article Information

The authors report no financial relationships with commercial interests.

Supported by the NIMH Intramural Research Program.

From the Emotion and Development Branch and the Scientific and Statistical Computing Core, NIMH, Bethesda, Md.

Address correspondence to Dr. Deveney (deveneycm@mail.nih.gov).

Copyright © 2013 by the American Psychiatric Association

Received July 14, 2012; Revised January 11, 2013; Accepted February 14, 2013.

Abstract

Objective  Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation.

Method  The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions.

Results  Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation group’s responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups.

Conclusions  In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.

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FIGURE 1. Schematic of Trial Structure During the Frustration Condition (Game 3)a

a The blue cue and the black target could appear in either the left or the right box. On valid trials, the cue and target were in the same location. On invalid trials, the cue and target were in opposite locations. Participants were instructed to press a button corresponding to the target location. During game 3, which was the frustration condition, participants viewed money trials and no-money trials that were distinguished by different trial type indicators (green “$$$” versus yellow “000”) and the possibility of winning and losing money. During money trials, participants won or lost money depending on performance. During no-money trials, no money was won or lost. For both money and no-money trials in the frustration condition, 40% of correct responses were followed by positive feedback (either “You win” or “Good job”), and 60% of correct responses were followed by negative feedback (“Too slow”). All incorrect responses received negative feedback (“Wrong”).

FIGURE 2. Reaction Time to Identify a Target on Valid and Invalid Trials During the Frustration Condition (Game 3)a

a All participants responded more slowly on invalid compared with valid trials; however, children with severe mood dysregulation were slower on invalid trials than were healthy comparison children (p<0.05).

FIGURE 3. Brain Activation in Children With Severe Mood Dysregulation and Healthy Comparison Children on Positive and Negative Feedback Trialsa

a Panel A shows activation in the left posterior cingulate and precuneus (Talairach coordinates, x=−19, y=−55, z=32). Panel B shows activation in the left insula (Talairach coordinates, x=−28, y=−22, z=20). Images are displayed according to radiologic convention (left=right). BOLD=blood-oxygen-level-dependent.

b Significantly different (p<0.05).

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TABLE 1.Demographic and Clinical Characteristics of Children With Severe Mood Dysregulation and Healthy Comparison Children
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a Wechsler Abbreviated Scale of Intelligence (two-scale IQ).

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b Significant difference between groups, p<0.04.

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c ADHD=attention deficit hyperactivity disorder.

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TABLE 2.Significant Findings From the Group-by-Feedback Interaction Observed in the Whole-Brain fMRI Analysis
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a Cluster size was determined using a significance threshold of p<0.05, corrected for the number of comparisons.

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b Coordinates refer to the voxel with maximum signal intensity.

Table Footer Note

c Statistics refer to the analysis of the extracted clusters in SPSS; df=1, 39.

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References

Leibenluft  E;  Charney  DS;  Towbin  KE;  Bhangoo  RK;  Pine  DS:  Defining clinical phenotypes of juvenile mania.  Am J Psychiatry 2003; 160:430–437
[CrossRef] | [PubMed]
 
Leibenluft  E:  Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths.  Am J Psychiatry 2011; 168:129–142
[CrossRef] | [PubMed]
 
Safer  DJ:  Irritable mood and the Diagnostic and Statistical Manual of Mental Disorders.  Child Adolesc Psychiatry Ment Health 2009; 3:35
[CrossRef] | [PubMed]
 
Lewis  MD;  Lamm  C;  Segalowitz  SJ;  Stieben  J;  Zelazo  PD:  Neurophysiological correlates of emotion regulation in children and adolescents.  J Cogn Neurosci 2006; 18:430–443
[CrossRef] | [PubMed]
 
Lewis  MD;  Stieben  J:  Emotion regulation in the brain: conceptual issues and directions for developmental research.  Child Dev 2004; 75:371–376
[CrossRef] | [PubMed]
 
Moadab  I;  Gilbert  T;  Dishion  TJ;  Tucker  DM:  Frontolimbic activity in a frustrating task: covariation between patterns of coping and individual differences in externalizing and internalizing symptoms.  Dev Psychopathol 2010; 22:391–404
[CrossRef] | [PubMed]
 
Rich  BA;  Carver  FW;  Holroyd  T;  Rosen  HR;  Mendoza  JK;  Cornwell  BR;  Fox  NA;  Pine  DS;  Coppola  R;  Leibenluft  E:  Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation.  J Psychiatr Res 2011; 45:1283–1294
[CrossRef] | [PubMed]
 
Rich  BA;  Holroyd  T;  Carver  FW;  Onelio  LM;  Mendoza  JK;  Cornwell  BR;  Fox  NA;  Pine  DS;  Coppola  R;  Leibenluft  E:  A preliminary study of the neural mechanisms of frustration in pediatric bipolar disorder using magnetoencephalography.  Depress Anxiety 2010; 27:276–286
[CrossRef] | [PubMed]
 
Rich  BA;  Schmajuk  M;  Perez-Edgar  KE;  Fox  NA;  Pine  DS;  Leibenluft  E:  Different psychophysiological and behavioral responses elicited by frustration in pediatric bipolar disorder and severe mood dysregulation.  Am J Psychiatry 2007; 164:309–317
[CrossRef] | [PubMed]
 
Rich  BA;  Schmajuk  M;  Perez-Edgar  KE;  Pine  DS;  Fox  NA;  Leibenluft  E:  The impact of reward, punishment, and frustration on attention in pediatric bipolar disorder.  Biol Psychiatry 2005; 58:532–539
[CrossRef] | [PubMed]
 
Klöppel  S;  Stonnington  CM;  Petrovic  P;  Mobbs  D;  Tüscher  O;  Craufurd  D;  Tabrizi  SJ;  Frackowiak  RS:  Irritability in pre-clinical Huntington’s disease.  Neuropsychologia 2010; 48:549–557
[CrossRef] | [PubMed]
 
LeDoux  JE:  The Emotional Brain .  New York,  Simon and Shuster, 1996
 
Schultz  W:  Dopamine signals for reward value and risk: basic and recent data.  Behav Brain Funct 2010; 6:24
[CrossRef] | [PubMed]
 
Schultz  W;  Dayan  P;  Montague  PR:  A neural substrate of prediction and reward.  Science 1997; 275:1593–1599
[CrossRef] | [PubMed]
 
Brotman  MA;  Rich  BA;  Guyer  AE;  Lunsford  JR;  Horsey  SE;  Reising  MM;  Thomas  LA;  Fromm  SJ;  Towbin  K;  Pine  DS;  Leibenluft  E:  Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder.  Am J Psychiatry 2010; 167:61–69
[CrossRef] | [PubMed]
 
Adleman  NE;  Kayser  R;  Dickstein  D;  Blair  RJ;  Pine  D;  Leibenluft  E:  Neural correlates of reversal learning in severe mood dysregulation and pediatric bipolar disorder.  J Am Acad Child Adolesc Psychiatry 2011; 50:1173–1185.e2
[CrossRef] | [PubMed]
 
McManis  MH;  Bradley  MM;  Berg  WK;  Cuthbert  BN;  Lang  PJ:  Emotional reactions in children: verbal, physiological, and behavioral responses to affective pictures.  Psychophysiology 2001; 38:222–231
[CrossRef] | [PubMed]
 
Cox  RW:  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages.  Comput Biomed Res 1996; 29:162–173
[CrossRef] | [PubMed]
 
Corbetta  M;  Kincade  JM;  Ollinger  JM;  McAvoy  MP;  Shulman  GL:  Voluntary orienting is dissociated from target detection in human posterior parietal cortex.  Nat Neurosci 2000; 3:292–297
[CrossRef] | [PubMed]
 
Mischel  W;  Shoda  Y;  Rodriguez  MI:  Delay of gratification in children.  Science 1989; 244:933–938
[CrossRef] | [PubMed]
 
Morasch  KC;  Bell  MA:  Self-regulation of negative affect at 5 and 10 months.  Dev Psychobiol 2012; 54:215–221
[CrossRef] | [PubMed]
 
Morris  AS;  Silk  JS;  Morris  MD;  Steinberg  L;  Aucoin  KJ;  Keyes  AW:  The influence of mother-child emotion regulation strategies on children’s expression of anger and sadness.  Dev Psychol 2011; 47:213–225
[CrossRef] | [PubMed]
 
Reijntjes  A;  Stegge  H;  Terwogt  MM;  Kamphuis  JH;  Telch  MJ:  Emotion regulation and its effects on mood improvement in response to an in vivo peer rejection challenge.  Emotion 2006; 6:543–552
[CrossRef] | [PubMed]
 
Rothbart  MK;  Ahadi  SA;  Hershey  KL;  Fisher  P:  Investigations of temperament at three to seven years: the Children’s Behavior Questionnaire.  Child Dev 2001; 72:1394–1408
[CrossRef] | [PubMed]
 
Alia-Klein  N;  Goldstein  RZ;  Tomasi  D;  Woicik  PA;  Moeller  SJ;  Williams  B;  Craig  IW;  Telang  F;  Biegon  A;  Wang  GJ;  Fowler  JS;  Volkow  ND:  Neural mechanisms of anger regulation as a function of genetic risk for violence.  Emotion 2009; 9:385–396
[CrossRef] | [PubMed]
 
Alia-Klein  N;  Goldstein  RZ;  Tomasi  D;  Zhang  L;  Fagin-Jones  S;  Telang  F;  Wang  GJ;  Fowler  JS;  Volkow  ND:  What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex.  Emotion 2007; 7:649–659
[CrossRef] | [PubMed]
 
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Which of the following are criteria for severe mood dysregulation but not disruptive mood dysregulation disorder?
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Youths with severe mood dysregulation were characterized by abnormally reduced activation in response to negative feedback in what regions?
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