Reward-Related Neural Substrates of Irritability: A Task-Based fMRI Study of Early Childhood

OBJECTIVE: Irritability, conceptualized as elevated proneness to anger, is a transdiagnostic feature and robust predictor of multiple psychological disorders. Identifying neurophenotypes of irritability in early childhood is critical to inform timely intervention, as irritability persisting into school age is associated with increased psychopathology and impairment. The present study aimed to examine the neural substrates of irritability in early childhood in relation to reward processing, which is implicated in multiple disorders. METHOD: Data from 185 children (mean [SD] age = 6.16 [0.50] years) were included. The children completed a child-friendly version of the monetary incentive delay task while undergoing functional magnetic resonance imaging to assess neural activity during reward anticipation (ie, reward vs no reward) and feedback (ie, hit vs miss the target with a reward expected vs not). The Multidimensional Assessment Profiles-Temper Loss Scale assessed irritability. Whole-brain multilevel analysis of neural activation and functional connectivity examined associations between irritability and reward processing. RESULTS: Greater irritability was associated with greater differences in response to reward vs no reward, reflected in left putamen activation. It was also associated with alterations in amygdala and striatal connectivity with multiple frontotemporal and parietal regions. The directionality of the effects varied depending on task-specific conditions (eg, hitting a target with reward expected, missing a target with no reward expected). CONCLUSION: The present findings provide insights into the reward-related neural pathways of irritability in early childhood, a critical yet understudied developmental stage, which has the potential to facilitate timely and mechanistically informed interventions in young children.