Fig. 1

Experimental protocol for long-term (1 year) alcohol consumption and neuromodulation in the ADE rat model. (A) Alcohol was freely available for the first 8 weeks, followed by periods of free access and deprivation of variable lengths to prevent habituation. (B) Following the final (8th) alcohol drinking cycle, the animals were habituated to the recording setup and underwent stereotactic surgery to implant the neuroprosthetic interface above the medial PFC encompassing anterior cingulate (ACC), prelimbic (PrL) and infralimbic (IL) cortices. The stimulation electrode was located 3.2 mm anterior to bregma. Bilateral stimulation was delivered epidurally as biphasic, charge-imbalanced rectangular pulses (100 µA/-80 µA, 130 Hz, 100 µs pulse width) for 20 min right before recording. (C) Animals underwent initial electrocorticographic (ECoG) recordings during a passive two-tone auditory oddball paradigm 2 weeks following the last consumption of alcohol and three days postsurgery, with a subsequent session following stimulation another three days later. (D) Exemplary grand average data derived from the frontocentral stimulation electrode site, illustrating deviant-minus-standard difference ERP (left) and ERO (right) (analyzed as event-related spectral perturbation (ERSP) in decibels (dB)) across delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz) and gamma (> 30 Hz) frequency ranges before (top) and after (bottom) neuromodulation, highlighting stimulation-induced neuroenhancement. ERP figures further illustrate habituation to frequent standard sounds, as indicated by the flattened neural response, which remains unaffected by stimulation.