Background: Compulsive alcohol use, the tendency to continue alcohol seeking and taking despite negative consequences, is a hallmark of alcohol use disorder. Preclinical rodent studies have suggested a role for the medial prefrontal cortex, anterior insula, and nucleus accumbens in compulsive alcohol seeking. It is presently unknown whether these findings translate to humans. We used a novel functional magnetic resonance imaging paradigm and tested the hypothesis that heavy drinkers would compulsively seek alcohol despite the risk of an aversive consequence, and that this behavior would be associated with the activity of frontostriatal circuitry.
Methods: Non-treatment-seeking heavy and light drinkers (n = 21 per group) completed a functional magnetic resonance imaging paradigm in which they could earn alcohol or food points at various threat levels (i.e., various probabilities of incurring an aversive consequence). Brain function was evaluated when individuals had the opportunity to earn reward points at the risk of an aversive consequence, an electric shock on the wrist.
Results: Compared with light drinkers, heavy drinkers attempted to earn more aversion-paired alcohol points. Frontostriatal circuitry, including the medial prefrontal cortex, anterior insula, and striatum, was more active in this group when viewing threat-predictive alcohol cues. Heavy drinkers had increased connectivity between the anterior insula and the nucleus accumbens. Greater connectivity was associated with more attempts to earn aversion-paired alcohol points and self-reported compulsive alcohol use scores.
Conclusions: Higher activation of frontostriatal circuitry in heavy drinkers may contribute to compulsive alcohol seeking. Treatments that disrupt this circuitry may result in a decrease in compulsive alcohol use.
Trial registration: ClinicalTrials.gov NCT02119624.
Keywords: Alcohol use disorder; Anterior insula; Compulsivity; Medial prefrontal cortex; Neuroimaging; Nucleus accumbens.
Published by Elsevier Inc.