Research Component 4: McTeague Liu & Book

mPFC Theta Burst Stimulation as a Treatment Tool for Alcohol Use Disorder: Effects on Drinking and Incentive Salience

Principal Investigator: Lisa McTeague, Ph.D.
Co-Investigator: Hesheng Liu, Ph.D.
Co-Investigator: Sarah W. Book, M.D.

This research component builds on previous work in the ARC that involved examining the capacity of transcranial magnetic stimulation (TMS) to blunt alcohol cue-induced brain activation (fMRI) and measures of craving in individuals with AUD. This project extends this work to evaluate the therapeutic potential of this novel intervention in a clinical outpatient treatment setting. Treatment-seeking individuals with AUD recruited via the ARC Clinical Intake & Assessment Core will receive a 4-week treatment regimen of theta burst stimulation (TBS) targeting the mPFC. Alcohol drinking (self-report and biomarker indices) will be assessed at monthly follow-ups, and neuroimaging indices (pre- vs. post-treatment) will be used to assess alcohol reward-blunting and negative affect components of AUD. Hypotheses to be tested are that mPFC-targeted TBS, compared to sham control, will: (a) improve AUD treatment (drinking) outcomes; (b) reduce alcohol cue reactivity and reward circuit (cortico-limbic-striatal) functional connectivity; and (c) normalize enhanced reward circuit reactivity to alcohol vs. naturalistic reward cues and enhanced reactivity to aversive (threat) cues. The overall goal is to evaluate the efficacy of mPFC-targeted TBS in improving AUD treatment outcomes and determine whether neurocircuit-based reductions in incentive salience bias to alcohol cues mediate the clinical outcomes.

Specific Aims of the project include:

• Test the hypothesis that active TBS to vmPFC, relative to sham, will result in fewer heavy drinking days and more abstinence days, as indicated by both self-report and objective (biomarker) measures.
• Test the hypothesis that at baseline participants will demonstrate increased activation foremost in vmPFC and striatal regions (i.e., reward circuitry) during exposure to alcohol cues, and that active relative to sham stimulation will result in reduced alcohol (cue) reward circuit activation (ventral striatum, vmPFC), an effect that will mediate TMS effects on drinking outcomes.
• Test the hypothesis that active compared to sham TBS, will “normalize” motivational neurocircuit responses, as evidenced by reduced responses to alcohol cues to a level similar to naturalistic reward cue reactivity, along with reduced reactivity to naturalistic threat cues.