Chronic alcohol-induced brain states limit propagation of direct cortical stimulation

The impact of chronic alcohol consumption is evident in disruptions within prefrontal circuitries, resulting in cognitive and behavioral deficits that underlie lost control over drinking. Given the limited efficacy of current pharmacotherapy, we employed multifunctional bioelectronics to investigate the potential of direct electrical brain stimulation to rectify neural impairments in alcohol-dependent rats. Cortical stimulation counteracted the observed deficiencies in event-related brain potentials and neural oscillations following chronic alcohol consumption, particularly strengthening low-beta oscillations related to executive control. Stimulation efficacy thereby correlated with individual drinking patterns. In alcohol-dependent rats, stimulation-related neuroenhancement was spatially confined to the stimulation site, indicative of reduced neural connectivity as confirmed by a computational approach to directed functional connectivity patterns. Such state-dependent factors may contribute to the varying efficacy of brain stimulation observed in patients, ultimately suggesting personalized neuromodulation designs.