Longitudinal investigation of TMS as a tool to improve alcohol treatment outcomes

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With advances in optogenetic stimulation techniques, preclinical studies have demonstrated that activity in frontal-striatal neural circuits has a causal influence on heavy drinking and alcohol reinstatement. Clinically, however, we have not yet translated this research into a neural circuit based therapeutic technique for patients with alcohol use disorder (AUD). The long term goal of our multidisciplinary research team is to determine the optimal parameters through which non- invasive theta burst stimulation (TBS – a patterned form or transcranial magnetic stimulation) can be used to improve alcohol drinking outcomes (abstinence, heavy drinking days) among individuals seeking behavioral treatment for AUD. Building on a foundation of several target identification studies and a small double blinded clinical trial in treatment-engaged AUD patients by our group, here we propose a double-blind placebo controlled, randomized study to evaluate the relative efficacy of 2 potential TBS treatment strategies for alcohol use disorder. Specifically, using the existing infrastructure of the MUSC Intensive Outpatient treatment Program, consenting participants will be randomized to receive real or sham TBS delivered to the ventral medial prefrontal cortex (mPFC), or dorsolateral prefrontal cortex (dlPFC) for 20 sessions (2x/day, 10 days) immediately before their daily intensive outpatient therapy sessions. The scientific premise of this 5 year R01 proposal is that, by modulating the neural circuits that regulate alcohol cue-reactivity (Strategy 1, Aim 1, mPFC) or executive control (Strategy 2, Aim 2, dlPFC) it will be possible to increase alcohol abstinence rates and decrease heavy drinking days over a 4 month period. With our combined scientific expertise in brain stimulation (Hanlon, neuroimaging (Schacht and Hanlon), alcohol use disorder research (Schacht, Anton, Book), and clinical practice with AUD patients (Book, Smith) our research team at MUSC is uniquely suited to develop this critical line of research. The outcomes of these Aims will provide an evidence-based foundation for a multisite clinical trial and will hasten progress towards developing a new neural circuit based treatment for patients with AUD.