Risk-related decision making evokes distinct brain activation patterns in reward evaluation regions in substance use naïve versus non-naïve adolescents

Identifying brain and behavioral precursors to substance use (SU) may guide interventions that delay initiation in youth at risk for SU disorders (SUD). Heightened reward-sensitivity and risk-taking may confer risk for SUD. In a longitudinal, prospective study, we characterized behavioral and neural profiles associated with reward-sensitivity and risk-taking in substance-naive adolescents, examining whether they differed as a function of SU initiation at 18- and 36-months follow-up. Adolescents (N=70; 11.1-14.0 years) completed a reward-related decision-making task (Wheel of Fortune (WOF)) while undergoing functional MRI. Measures of reward sensitivity (Behavioral Inhibition System-Behavioral Approach System; BIS-BAS), impulsive decision-making (delay discounting task), and SUD risk (Drug Use Screening Inventory, Revised (DUSI-R)) were collected at baseline. Baseline metrics were compared for youth who did (SI; n=27) and did not (SN; n=43) initiate SU at follow-up. While groups displayed similar discounting and risk taking behavior, SI youth showed more variable patterns of activation in left insular cortex during high-risk selections, and left anterior cingulate cortex in response to rewarded outcomes. SI participants scored higher on the DUSI-R and BAS subscales. Results suggest differences in brain regions critical in the development and experience of SUDs may precede SU and serve as a biomarker for SUD risk.