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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.


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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