ABSTRACT: Alcohol misuse is associated with thalamic dysfunction. The thalamus comprises subnuclei that relay and integrate information between cortical and subcortical structures. However, it is unclear how the subnuclei contribute to thalamic dysfunctions in problem drinking. We investigated resting-state functional connectivity (rsFC) of thalamic subregions in 107 nondependent drinkers (57 women), using masks delineated by white matter tractography. Thalamus was parceled into motor, somatosensory, visual, premotor, frontal association, parietal association, and temporal association subregions. Whole-brain linear regression, each against Alcohol Use Disorders Identification Test (AUDIT) and positive alcohol expectancy (AE) score with age as a covariate, was performed for each seed, for men and women combined, and separately. Overall, problem drinking was associated with increased thalamic connectivities, whereas AE was associated with a mixed pattern of increased and decreased connectivities. Motor, premotor, somatosensory, and frontal association thalamic connectivity with bilateral caudate head was positively correlated with AUDIT score in men and women combined. Connectivity of the right caudate head with frontal association and premotor thalamus was also positively correlated with AE score in men and women combined. In contrast, motor and premotor thalamic connectivity with a number of cortical and subcortical structures showed sex differences in the correlation each with AUDIT and AE score. In mediation analyses, AE score completely mediated the correlation between thalamic caudate connectivity and AUDIT score, whereas the model where AE contributed to problem drinking and, in turn, altered thalamic caudate connectivity was not supported. To conclude, thalamic subregional rsFCs showed both shared and distinct changes and sex differences in association with problem drinking and AE. Increased thalamic caudate connectivity may contribute to problem drinking via enhanced AE. The findings suggest the importance of examining thalamic subdivisions and sex in investigating the functional roles of thalamus in problem drinking.
