A network-based brain stimulation paradigm for alcohol use disorder with co-occurring major depressive disorder: a...

Alcohol use disorder (AUD) is frequently complicated by co-occurring major depressive disorder (MDD), a comorbidity associated with greater clinical severity, elevated relapse risk, and poorer treatment outcomes than either condition alone. Despite the prevalence and burden of this dual diagnosis, interventions that simultaneously address alcohol use and depressive symptoms show limited effectiveness. Converging evidence from neuroimaging and translational research indicates that AUD and MDD share disruptions across large-scale brain networks involved in salience processing, attentional control, and affect regulation. In this Mini Review, we synthesize the literature on transcranial magnetic stimulation (TMS) in AUD, highlighting dominant region-centric paradigms (including those adapted from major depressive disorder), methodological heterogeneity, and ongoing uncertainties regarding optimal targets and mechanisms of action. We then outline a network-based framework centered on the ventral attention network (VAN) as an alternative neuromodulation approach for AUD with co-occurring MDD. Drawing on attention neuroscience and systems-level models of addiction, we emphasize the temporoparietal junction as a theoretically grounded and neuromodulation-accessible entry point for probing VAN responsivity and plasticity. By reframing TMS as a mechanistic probe of network dynamics rather than solely as a therapeutic intervention, this perspective provides a foundation for developing more precise, biologically grounded approaches to addressing heterogeneity and relapse vulnerability in this clinically complex population.