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

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 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 performed by our group, here we propose a double-blind
placebo controlled, randomized study to evaluate the relative efficacy of 2 potential TMS
treatment strategies for AUD. Specifically, using the existing infrastructure of the MUSC Intensive
Outpatient Treatment Program, consenting participants will be randomized to receive real or sham
TMS delivered to the ventral medial prefrontal cortex (vmPFC), 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, vmPFC) 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 the proposed
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.

Grant Number: 5R01AA027705-06
NIH Institute/Center: NIH
Principal Investigator: Merideth Addicott