Abstract| Volume 16, ISSUE 1, P115-116, January 2023

A 12 step journey to find a (TMS) treatment for drug and alcohol addiction: from discovery science to clinical trials

      Nearly 3 million people die annually from alcohol abuse. While several pharmaceutical options are available, the side effects are high and medication is not well-tolerated. Through recent innovations in neuroimaging and neuromodulation we, as a scientific community, are now uniquely positioned to evaluate transcranial magnetic stimulation (TMS) as a novel, non-invasive therapeutic tool to help improve the lives of people with alcohol use disorder (AUD).
      This talk will cover a series of 12 decision making steps that led from discovery science to clinical trials in AUD. The talk will integrate studies from multiple laboratories and highlight moments that led us to rethink our hypotheses as well as findings that moved us forward. Briefly, our first step was to identify the neural circuits of interest (Target Identification). This led to a focus on frontal-striatal connectivity to the dorsolateral prefrontal cortex and the medial prefrontal cortex (MPFC). Using interleaved TMS-BOLD imaging, we then determined which target was more uniformly disrupted (Target Selection). Focusing on the MPFC, it became clear that neural architecture would be important to TMS dosing (Methods Refinement). Initial proof of principle data with a single session of TMS (Target Engagement) led to a double-blind sham controlled clinical trial. This created questions regarding the optimal “brain state” or provocation for TMS therapeutic approaches (Methods Refinement). As the field moves forward planning multisite trials, we have begun to appreciate the importance of gender, age, and the overlap between the TMS-induced electric field and the individual’s endogenous brain activity as salient factors in treatment response.
      This talk is designed to highlight a systematic path for TMS treatment development. This path is not strictly linear, not necessarily optimal, nor exclusive. It is however, an intentional, well-reasoned, and empirically-derived pathway which may serve as scaffolding for translating academic discovery into real-world therapeutic options.