Assessing the Impact of dTMS on Neural Targets Associated with Alcohol Use Disorder - ABSTRACT Background: Converging lines of evidence suggest that neuromodulation of the neural mechanisms underlying alcohol use disorder (AUD) are an innovative next step in improving treatment outcomes and reducing risk of relapse. Emerging research supports the salience network (SN) as a promising target to accomplish these goals. Deep transcranial magnetic stimulation (dTMS) is one type of neuromodulation technique that allows for deeper stimulation of cortical neurons, thus reaching core nodes of the SN, such as the dorsal anterior cingulate cortex (dACC). Objective: The aim of this proposal is to 1) evaluate the efficacy of active dTMS in increasing dACC activation and reducing drinking relative to a sham (placebo) condition, 2) to assess the trajectory of target engagement changes (i.e., increased dACC activation) that are evident after 15 sessions versus 30 sessions, and 3) evaluate the durability of the neural changes and how this might impact treatment outcomes (i.e., % days abstinent and % heavy drinking days). Methods/Design: We will enroll 100 adults with AUD into a 2-arm randomized, double-blind, sham-controlled mechanistic trial to confirm target engagement relative to sham, assess the impact of the protocol on drinking behaviors, and determine moderators of treatment response. Participants will be randomized in a 1:1 ratio to receive either 30 sessions of active 20Hz dTMS to the mPFC and dACC using the H7 coil, or an equivalent sham condition. Participants will receive 3 dTMS treatments per day for 10 consecutive business days (30 total treatment sessions) and will complete neuroimaging assessments at baseline, after one-half of treatment sessions, post-treatment and 1 month after treatment. Specific Aims: We aim 1) to evaluate the efficacy of active dTMS relative to sham dTMS in reducing 3-month post-treatment drinking rates and target engagement, 2) evaluate the relationship between degree of target engagement to drinking rates and identify individual variability in target engagement trajectory, and 3) to evaluate the association of target engagement durability of dTMS for relapse prevention. Impact: The proposed research will elucidate mechanisms of brain and behavior change, accelerate the development of new, device-based, treatment options and will be the basis for developing a large-scale, dose- varying, clinical trial to test new treatment strategies for AUD.
