Description
Purpose: Irritability, conceptualized as a lowered threshold for frustration in response to blocked goal attainment (i.e., frustrative non-reward), is a common, detrimental symptom in adolescence that predicts continued impairment into adulthood. Yet, the neural mechanisms of irritability are not well understood. This study aims to identify irritability related neural patterns, specifically activation and amygdala connectivity, using a novel frustrative non-reward paradigm. Participants: This study used a sample of N=31 youth participants, ages 11-18 years (M=14.53, SD=1.74) and enriched for irritability via history of complex trauma. The majority (83.87%) of youth participants identified as Hispanic/Latinx; 58.06% identified as female. Methodology: Irritability was measured using the youth-reported version of the Affective Reactivity Index. During fMRI acquisition, the adolescent participants performed a “rigged” child-friendly monetary incentive delay task, which provided incorrect, negative feedback on performance. Individual level models estimated brain activation and functional connectivity for each condition (reward blocked, reward received) as well as the “bleed- through” effect into the next trial. Whole brain, voxel-wise group-level analyses for both activation and functional connectivity were conducted using 3dMVM ANCOVAs in AFNI, with irritability as the between-subjects variable and task condition as the within-subjects variable. It was hypothesized that brain activation/connectivity in frontostriatal reward/control networks were altered in individuals with higher levels of irritability, depending on trial condition. Results: Irritability was associated with alterations in amygdala connectivity with basal ganglia, prefrontal, temporal, and parietal regions, and in activation of prefrontal and posterior cortical structures. Across clusters, youths with greater irritability showed activation/connectivity differences between reward blocked vs. received conditions in the opposite direction compared to youths with lowered irritability. Alterations in amygdala- temporoparietal connectivity and lingual gyrus activation were apparent after feedback, “bleeding through” into the subsequent trial. Conclusions: These findings support the central role of frustrative non-reward as a key irritability pathway evidenced by neural aberrations. This work is one of the first to document neural correlates of difficult recovery from frustration characteristic of irritability and provides a path toward identifying novel treatment targets for irritability in diverse populations.
