Adolescent substance use and functional connectivity between the ventral striatum and hippocampus

Neurodevelopmental explanations for adolescent substance use have focused on heightened sensitivity of the brain9s reward system, centered around the ventral striatum (VS). Recent evidence demonstrates increased functional connectivity between the VS and hippocampus in adolescents relative to adults, suggesting that the adolescent brain may learn from subsequent exposure to risks/rewards. However, a link between VS-hippocampal circuitry and adolescent substance use has yet to be established. Two separate longitudinal studies were conducted to evaluate whether variation in VS-hippocampal resting-state functional connectivity (rs-FC) predicts subsequent adolescent substance use. Study 1 consisted of 19 youth recruited from a high sociodemographic risk population (N=19; 14 female; 47% Black non-Hispanic; 32% White Non-Hispanic). To replicate results of Study 1, Study 2 utilized data from the National Consortium on Adolescent Neurodevelopment and Alcohol, an ongoing multi-site imaging study (N = 644; 339 female; 11% Black Non-Hispanic, 11% Hispanic/Latino, 66% White Non-Hispanic). Resting-state fMRI data were collected at a baseline time point and lifetime and past year self-reported substance use was collected at a follow up visit. Regression models tested whether baseline VS-hippocampal rs-FC predicted substance use at follow up. Across both studies, higher VS-hippocampal rs-FC at baseline predicted greater substance use at follow up. These data provide the first evidence linking increased VS-hippocampal connectivity with greater adolescent substance use. Results fit with the emerging idea that adolescent substance use is driven by not only a heightened sensitivity to reward, but also a stronger link between reinforcement learning and episodic memory for rewarding outcomes.