Resting-state frontostriatal dysconnectivity and cognitive impairment in alcohol use disorder

Alcohol use disorder (AUD) involves persistent craving and cognitive deficits, reflecting an imbalance between reward/habit systems and cognitive control. This study used resting-state functional connectivity (rsFC) to identify prefrontal-striatal circuits related to cognitive and clinical dimensions in AUD.

Sixty-six male patients with AUD and 43 male healthy controls completed craving assessments, MATRICS Consensus Cognitive Battery testing, and resting-state fMRI. Seed-based rsFC analyses were conducted for the dorsolateral prefrontal cortex (DLPFC), nucleus accumbens, and dorsal striatum (DS). Group differences and correlations with cognition and craving were examined.

Compared with controls, patients with AUD showed poorer speed of processing, working memory, and reasoning/problem solving (all p < .05), but not verbal or visual learning. AUD was characterized by hypoconnectivity of DS and DLPFC with frontoparietal, temporal, and cerebellar regions. Within AUD, greater craving was associated with lower left DS-right supramarginal gyrus connectivity (r = -.267, p = .030). Poorer speed of processing was associated with greater right DLPFC-left orbital inferior frontal gyrus connectivity (r = -.289, p = .030). Poorer visual learning was associated with greater right DLPFC connectivity with the right middle temporal gyrus (r = -.268, p = .036) and right inferior temporal gyrus (r = -.259, p = .044).

AUD involves widespread DS- and DLPFC-related hypoconnectivity and distinct circuit-level associations with craving and cognition. These preliminary findings provide initial support for a dimensional circuit-based framework of AUD heterogeneity and suggest that right DLPFC-related connectivity may be relevant to cognitive dysfunction. However, these associations were exploratory and require independent replication before any intervention implications can be considered.