Accumbens functional connectivity during reward mediates sensation-seeking and alcohol use in high-risk youth

Background: Differences in fronto-striatal connectivity in problem substance users have suggested reduced influence of cognitive regions on reward-salience regions. Youth with a family history of alcoholism (FH+) have disrupted ventral striatal processing compared with controls with no familial risk (FH−). As sensation-seeking represents an additional vulnerability factor, we hypothesized that functional connectivity during reward anticipation would differ by family history, and would mediate the relationship between sensation-seeking and drinking in high-risk subjects. Methods: Seventy 18-22 year olds (49 FH+/21 FH−) performed a monetary incentive delay task during functional magnetic resonance imaging. Group connectivity differences for incentive (reward/loss) vs. neutral conditions were evaluated with psychophysiological interaction (PPI) analysis, seeded in nucleus accumbens (NAcc). Indirect effects of sensation-seeking on drinking volume through accumbens connectivity were tested. Results: NAcc connectivity with paracentral lobule/precuneus and sensorimotor areas was decreased for FH− vs. increased for FH+ during incentive anticipation. In FH+, task-related functional coupling between left NAcc and supplementary sensorimotor area (SSMA) and right precuneus correlated positively with sensation-seeking and drinking volume and mediated their relationship. In FH−, left NAcc-SSMA connectivity correlated negatively with sensation-seeking but was not related to drinking. Conclusions: These results suggest preexisting differences in accumbens reward-related functional connectivity in high-risk subjects. NAcc coupling with SSMA, involved in attention and motor networks, and precuneus, a default mode structure, appear to mediate sensation-seeking's effect on drinking in those most at-risk. Differences in accumbens connectivity with attention/motor/default networks, rather than control systems, may influence the reward system's role in vulnerability for substance abuse.