Left Ventral Caudate Functional Connectivity Mediates the Relationship Between Habitual Responding and Alcohol Use

Preclinical studies posit that habitual behaviour is an important mechanism in the development of alcohol use disorder (AUD), but human findings are unclear. The goals of this study were to test a behavioural measure of habit formation, the Slips of Action Task (SOAT), in humans and identify brain-based mechanisms explaining the relationship between habit and alcohol use. Thirty-six participants (63.9% female, mean age = 30.58, SD = 9.73, 69.4% White, 83.3% Not Hispanic/Latino) who endorsed heavy drinking completed self-report measures, the SOAT (lower scores = higher habit formation), a 2.5-h intravenous alcohol self-administration session, and a resting-state functional magnetic resonance imaging scan. Three seed regions-bilateral ventral caudate, nucleus accumbens and dorsal caudate-were assessed for significant whole brain functional connectivity (FC) associations with SOAT (cluster-level p_FWE < 0.05 at a cluster-forming threshold p = 0.001). Two clusters survived Bonferroni correction (cluster p_FWE = 0.008): FC between the left ventral caudate and the left middle frontal gyrus correlated negatively, while FC between the left NAc and the right central operculum correlated positively, with SOAT score. SOAT score was unrelated to drinking outcomes; however, there was a significant indirect relationship between SOAT and average drinks per drinking day through FC between the left ventral caudate and the left middle frontal gyrus. A similar trend seen with cumulative work for alcohol fell short of significance. Habit formation's relationship with alcohol use may function through neuroadaptations in the ventral caudate. More work is needed to better characterize objective habit formation in the human alcohol laboratory with additional laboratory-, alcohol-specific, imaging- and ambulatory-based alcohol use metrics.