UC San Diego

Rationale. Irritability is highly impairing and prevalent in pediatric psychopathology and typical development, yet underlying mechanisms and ameliorating factors are largely unknown. Irritability is associated with altered neural reward processing, including neural networks related to cognitive control, and better cognitive control has been hypothesized to mitigate irritability. To test this hypothesis, this study evaluated the relationship of executive functioning (EF; a measurable form of cognitive control) with irritability-related neural correlates of reward processing in youths with varying levels of irritability. Design. An archival dataset of 51 youths with a history of or at risk for mood disorders was used (age range = 9-19; mean age = 13.80 years, SD = 1.94). Irritability and EF were measured via the Affective Reactivity Index and the NIH Toolbox, respectively. Neural reward processing was measured via a monetary incentive delay task during fMRI acquisition: participants “hit” a target to obtain a potential reward. Neural activation across the entire brain, and ventral striatum (VS) and amygdala connectivity with the rest of the brain, were measured during reward anticipation and performance feedback. Multivariate general linear models, controlling for age, examined whether EF moderates the relationship between irritability and neural reward processing, separately for anticipation and performance feedback. Results. EF moderated irritability-related neural patterns during anticipation and performance feedback. In some brain areas/networks (VS-cuneus connectivity during anticipation; limbic activation and amygdala-temporal connectivity during performance feedback) differences were found regardless of task conditions: the combination of higher irritability and lower EF was associated with hyperactivation and hypoconnectivity, whereas the combination of higher irritability and higher EF was associated with the opposite pattern. In other areas/networks (cuneus activation during anticipation; frontal, limbic, temporal activation, and right VS-frontal connectivity during performance feedback), neural patterns depended on task condition and were generally opposite for higher irritability combined with lower EF versus higher irritability combined with higher EF. Conclusions and Implications. This study is a step toward understanding the interaction of top-down EF processes in pediatric irritability, which provides the necessary groundwork to build mechanistic interventions.