Blunted reward-related striatal activity and behavioral disinhibition as a pathway to adolescent cannabis and e-cigarette use

Introduction Adolescence is a period notable for increased risk-taking behaviors, including substance use (SU). Longitudinal work has linked behavioral disinhibition, particularly impulsive dispositions and externalizing tendencies with SU, but the underlying neurobiological manifestations remain less well-defined. This study examined whether individual differences in reward-related striatal activity and impulsivity predicted mental health (externalizing symptoms) and SU outcomes (cannabis, nicotine, alcohol) over a year later. Methods Adolescents ( n = 140; M age = 14.9 years) from a larger longitudinal cohort completed a Monetary Incentive Delay (MID) fMRI task at baseline along with a measure of self-reported impulsivity. At follow-up, they reported externalizing symptoms and days of cannabis, e-cigarette, and alcohol use. Task behavior response times [RTs, hit rates HRs] and striatal responses to anticipatory gain cues were extracted. Serial mediation models tested whether impulsivity and externalizing mediated an association between striatal activity and subsequent SU. Results Behaviorally, gain cues elicited faster target-related RTs and higher HRs (vs. loss or neutral trials), and performance scaled with incentive magnitude. Gain (vs. neutral) cues elicited greater bilateral caudate activity where more left caudate activity correlated with faster RTs and lower impulsivity. Serial mediation revealed that less left striatal activity during reward anticipation linked with higher impulsivity, which predicted more subsequent externalizing symptoms that, in turn, linked with more cannabis indirect effect = −0.01, 95%CI (−0.04, −0.001) and e-cigarette use days indirect effect = −0.02, 95%CI (–0.05, −0.004). No indirect or direct effects emerged for alcohol use. Conclusions These findings suggest blunted striatal activity may reflect reduced motivational drive for lower-intensity rewards (e.g., fictitious MID monetary gains), which contribute to SU vulnerability via heightened behavioral disinhibition in pursuit of higher-intensity stimulation. Intervention strategies that upregulate everyday reward value and strengthen self-regulation may offer utility in reducing teen SU.