Neurocognitive development of inhibitory control and substance use vulnerability

Previous research indicates that risk for substance use is associated with poor inhibitory control. However, it remains unclear whether at risk youth use follow divergent patterns of inhibitory control development. As part of the longitudinal National Consortium on Adolescent Neurodevelopment and Alcohol (NCANDA) study, participants (N = 113, baseline age: 12-21) completed a rewarded antisaccade task during fMRI, with up to three time points. We examined whether substance use risk factors, including dimensional measures of psychopathology (externalizing, internalizing) and family history of substance use disorder, were associated with developmental differences in inhibitory control performance and BOLD activation at both the trial-level and within individual antisaccade epochs (cue, preparation, and response). Among substance use risk factors, only externalizing psychopathology predicted developmental differences in inhibitory control, where high externalizing predicted lower correct response rates and faster latencies were observed in early adolescence, but normalized by late adolescence. Neuroimaging results revealed high externalizing was associated with developmentally-stable hypo-activation in the left middle frontal gyrus (trial-level), but divergent developmental patterns of posterior parietal cortex activation (cue epoch). Developmental differences in inhibitory control associated with externalizing suggest early adolescence may be a unique period of substance use vulnerability via cognitive and phenotypic disinhibition.\n\nHighlightsO_LICharacterized inhibitory control development in adolescents at-risk for substance use.\nC_LIO_LIExternalizing psychopathology is associated with lower antisaccade correct response rate and faster latencies in early adolescence.\nC_LIO_LIExternalizing performance differences normalize by late adolescence.\nC_LIO_LIExternalizing is associated with prefrontal hypo-activation across development.\nC_LIO_LIExternalizing moderates age-related increases in posterior parietal cortex activity.\nC_LI