Frontal-Striatal Reward Circuit Neuromodulation and Alcohol Self-Administration

Overview

This will be a single site randomized, 2-session, within-subject cross-over design pilot study. 20 enrolled (of 30 consented) subjects reporting varying levels of binge and high intensity drinking, defined as at least 2 episodes of drinking 4 (for women) or 5 (for men) drinks on an occasion over the last 5 weeks, (unless determined by PI that drinking history meets study objectives), will be enrolled. Subjects will be randomized to undergo one session of repetitive transcranial magnetic stimulation (rTMS) or sham immediately followed by the investigators rate control intravenous (IV) alcohol self-administration (ASA) paradigm. Subjects will then return 7-14 days later and undergo the same sequence of events with the opposite intervention (i.e. rTMS or sham) from session 1.

This pilot study intends to address the critical unmet need to develop novel treatments for alcohol use disorder (AUD), such as repetitive transcranial magnetic stimulation (rTMS), that directly impact drinking behavior. Binge drinking and high intensity drinking, or consumption meeting at least binge criteria, is a high-risk alcohol self-administration (ASA) pattern associated with the binge-intoxication stage of AUD and the rewarding effects of alcohol. The investigators propose to quantify the impact of medial prefrontal cortex (mPFC) rTMS on ASA using the investigators novel "rate-control" paradigm. The rate control paradigm allows subjects to determine how quickly their breath alcohol concentration (BrAC) will change (increase, decrease, or stay the same) over the next 3-5 minute epoch, at the end of which brief computer-assisted assay of craving for alcohol and subjective response attributed to alcohol's effect on stimulation, sedation, liking and well-being in a manner comparable to the Brief Biphasic Alcohol Effects Scale (BAES). Each assay requires less than 20 seconds to complete and will be administered during the last \~0.5 minutes of alcohol delivery but before selection of the next rate of exposure. The ensemble provides detailed self-administered time course of alcohol exposure and corresponding time-stamped series of quantified perceptions for analysis. This approach has demonstrated sensitivity in associating self-reported high intensity drinking and the time until a binge alcohol exposure of 80 milligrams per decilitre (mg/dL). The investigators premise is that clinically impactful neuromodulation should change ASA. Coupling rTMS to a laboratory-assessed ASA paradigm could document causal changes in drinking behavior attributable to modulation of specific neural circuits. The goal of this project is to generate preliminary data supporting the investigators central hypothesis - rTMS targeting to the mPFC, a primary cortical input to the frontal-striatal reward (FSR) circuit, will decrease the rate of alcohol self-administration.