Abstract

BackgroundIrritability, a relatively lowered threshold for anger, is prevalent in typically and atypically developing youths. Inhibitory control, the ability to suppress behaviors counter to goals, is essential for regulating emotions, including anger. Understanding how irritability relates to behavioral and neural markers of inhibitory control may inform interventions. MethodsYouths (N=52; mean age=13.78) completed a Flanker task on an iPad to measure behavioral correlates of inhibitory control; a subsample (n=19; mean age=13.21) additionally completed a similar task while undergoing fMRI acquisition to evaluate inhibitory control on a neural level. Irritability was measured using the Affective Reactivity Index. Associations between irritability and inhibitory control were evaluated behaviorally (via Pearson correlations), and neurally (via ANCOVAs with whole-brain activation and amygdala connectivity). ResultsfMRI results indicated that higher levels of irritability were associated with aberrant activation (in middle frontal gyrus, amygdala/parahippocampal gyrus, anterior cingulate, lentiform nucleus/striatum) and left amygdala connectivity (with middle temporal gyrus, parahippocampal gyrus, posterior cingulate, fusiform gyrus, and thalamus). Behavioral results were mixed. LimitationsLongitudinal studies are needed to characterize changes in neural circuitry and delineate whether the brain profiles precede or are a consequence of symptoms. Larger samples powered to examine multiple irritability-related symptom dimensions will be necessary to elucidate shared vs. disorder-specific irritability mechanisms. ConclusionsFindings suggest that pediatric irritability may be related to neural processes involving inhibitory control. Further, findings underscore the importance of neuroimaging in investigating symptom dimensions such as irritability, as neuroimaging may be more sensitive in detecting underlying abnormalities compared to behavioral data alone.

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