Amygdala-orbitofrontal functional connectivity mediates the relationship between sensation seeking and alcohol use among binge-drinking adults

Background: Decreased amygdala-orbitofrontal cortex (OFC) neural functional connectivity (FC) positively predicts alcohol use among adolescents. Low amygdala-OFC FC is also associated with poor emotion regulation, a trait robustly linked to alcohol use. Thus, decreased amygdala-OFC connectivity may represent a risk factor for the development of alcohol use disorder (AUD) via impaired emotion regulation or reward processing. In this study, we examined amygdala-OFC FC among young adult binge drinkers at high risk for AUD. We also tested if amygdala-OFC FC mediates the relationship between externalizing personality traits and alcohol use. Methods: Healthy male and female (n = 39) binge drinkers completed a resting state fMRI scan and the Eysenck Impulsive Personality questionnaire. We utilized seed-based connectivity of the left and right amygdala to prefrontal regions as well as mediation analysis. Results: Individuals with higher weekly alcohol use displayed decreased right amygdala-OFC FC. Furthermore, high trait venturesomeness, but not impulsivness, was associated with decreased right amygdala-OFC FC. Finally, right amygdala-OFC FC mediated the relationship between trait venturesomeness and weekly drinking; individuals with high trait venturesomeness displayed decreased right amygdala-OFC FC, which in turn predicted greater weekly drinking. Conclusions: Our findings corroborate and extend the adolescent literature by showing that decreased amygdala-OFC FC is associated with higher alcohol consumption among adults at elevated risk for AUD. This study also demonstrates for the first time that this neural profile reflects a tendency to sensation seeking. In sum, our findings suggest that amygdala-OFC FC may be an objective neural target for alcohol use prevention and intervention.