Sex differences in functional connectivity and behavior in a mouse model of alcohol abuse disorder: functional implication of Nucleus Accumbens.

Motivation: The complexity of alcohol abuse disorder (AUD) challenges mechanistic insights and limits therapeutic innovation, underscoring the need for targeted investigations to unravel neural signatures of AUD subtypes. Goal(s): To identify brain functional connectivity (FC) fingerprints linked to alcohol-consumption and examine how they differ across phenotypic subtypes and sexes, in a murine AUD model. Approach: Employing a translational animal-model of AUD combined with multimodal-MRI for analysis of brain connectome. Results: Multimodal stationary and dynamic FC analysis revealed prominent sex-dimorphism in connectome upon alcohol consumption and identified Nucleus-Accumbens functional lateralization as key-mediator of neuroplasticity changes dependent on sex- and phenotypic subtypes. Impact: Combining behavioral and functional connectivity analyses, enabled the identification of connectome profiles by sex and AUD subtype. Emphasizing the lateralized role of the Nucleus Accumbens, nuanced by sex and AUD subtype. These insights inform targeted sex- and phenotype-adapted AUD interventions.