Bidirectional links between adolescent brain function and substance use moderated by cognitive control

Background: No clear consensus exists as to whether neurodevelopmental abnormalities among substance users reflect predisposing neural risk factors, neurotoxic effects of substances, or both. Using a longitudinal design, we examined developmental patterns of the bidirectional links between neural mechanisms and substance use throughout adolescence. Method: 167 adolescents (aged 13–14 years at Time 1, 53% male) were assessed annually four times. Risk-related neural processing was assessed by blood-oxygen-level-dependent responses in the insula during a lottery choice task, cognitive control by behavioral performance during the Multi-Source Interference Task, and substance use by adolescents’ self-reported cigarette, alcohol, and marijuana use. Results: Latent change score modeling indicated that greater substance use predicted increased insula activation during risk processing, but the effects of insula activation on changes in substance use were not significant. The coupling effect from substance use to insula activation was particularly strong for adolescents with low cognitive control, which supports the theorized moderating role of cognitive control. Conclusions: Our results elucidate how substance use may alter brain development to be biased toward maladaptive decision-making, particularly among adolescents with poor cognitive control. Furthermore, the current findings underscore that cognitive control may be an important target in the prevention and treatment of adolescent substance use given its moderating role in the neuroadaptive effects of substance use on brain development.