The Effect of High Frequency rTMS to the Medial Prefrontal Cortex in Alcohol Use Disorder

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Project Summary In this application for a K23 Mentored Patient Oriented Research Career Development Award, Dr. Jonathan Wai proposes a comprehensive clinical study and training plan for development of an independent researcher with expertise in device-based treatments and neuroimaging for alcohol use disorder (AUD). This proposal seeks to study the effects of repetitive transcranial magnetic stimulation (rTMS) on alcohol self-administration and in vivo brain GABA levels in non-treatment seeking human participants with AUD. Previous studies have shown that AUD is associated with broad dysfunction in the prefrontal cortices, as well as decreased prefrontal GABA concentrations. Additionally, rTMS has been shown to increase prefrontal GABA in treatment studies with depressed patients, with the increase in GABA associated with clinical improvement. Early work using rTMS for AUD has shown that rTMS can decrease craving and reported alcohol use. Thus, rTMS to the prefrontal cortex may serve as a potential treatment for AUD, either alone or as an adjunct to existing treatments. We plan to conduct two sham-controlled, double-blinded, randomized human laboratory alcohol self- administration studies during the award period. For Study 1, AUD participants will be admitted to a research unit and randomized to receive active (n=22) or sham (n=22) rTMS. Participants will have an alcohol self- administration session and neuroimaging with magnetic resonance spectroscopy (MRS) before and after three weeks of rTMS. We will compare the number of choices for alcohol and brain GABA levels in AUD participants receiving active vs. sham rTMS. Study 2 (n=20) will be a pilot study using the same procedures, with the addition of naltrexone in both active and sham rTMS groups. In conducting this study and pursuing coursework and supervision from his mentors (Drs. Diana Martinez, Suzette Evans, and Christoph Juchem) and collaborators (Drs. Markus Heilig, Abraham Zangen, and Hanga Galfalvy), Dr. Wai will engage in an individualized training program to develop expertise in 1) Research with clinical rTMS, 2) Clinical research methods, 3) MRS acquisition and analysis methods, 4) Advanced biostatistics, and 5) Grant writing and management.