Alcohol Use Disorder (AUD) is prevalent, devastating, and difficult to treat. High relapse rates are likely due to factors that affect neural circuits that govern craving and cognitive control. There is growing interest in the utilization of prefrontal cortex repetitive transcranial magnetic stimulation (TMS) as a novel, non-invasive, non- pharmacologic approach to decreasing craving among individuals with alcohol use disorder (AUD). At this early stage of development, however, it is unclear if the best TMS strategy is to (1) attenuate activity in the medial prefrontal cortex (mPFC, which is involved in craving), or (2) amplify activity in the dorsolateral prefrontal cortex (dlPFC, which is involved in cognitive control). Several laboratories have demonstrated that a single session of 10 Hz TMS over the dlPFC leads to a decrease in craving for alcohol, nicotine, and cocaine. We have demonstrated that a single session of continuous theta burst (cTBS) TMS over the mPFC can also decrease craving, as well as the brain response to drug cues in cocaine users and alcohol users. The overarching goal of this proposal is to determine which of these brain stimulation strategies is more effective in decreasing functional activity (measured by BOLD signal) in limbic regions involved in alcohol craving (Aim 1), and decreasing self-reported craving (Aim 2). This will be achieved through a double-blind, sham-TMS controlled within-subject crossover study of individuals with AUD. Using functional MRI, the neural response to alcohol-cues (a task identical to that used in Research Project #2- Anton/Schacht) will be measured within 10 minutes after the participant receives a dose of continuous theta burst TMS to the mPFC, 10 Hz TMS to the dlPFC, or sham rTMS. Additionally, the effects of these TMS strategies on cortical neurochemistry will be measured using magnetic resonance spectroscopy (exploratory Aim 3), enabling us to relate the outcomes of these aims with complementary neurochemical information. The outcomes of this project will provide an evidence-based foundation for cortical target selection in future clinical trials of TMS as an innovative treatment strategy for individuals with AUD.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Medical University of South Carolina
United States
Zip Code
Zamudio-Bulcock, Paula A; Homanics, Gregg E; Woodward, John J (2018) Loss of Ethanol Inhibition of N-Methyl-D-Aspartate Receptor-Mediated Currents and Plasticity of Cerebellar Synapses in Mice Expressing the GluN1(F639A) Subunit. Alcohol Clin Exp Res 42:698-705
Cannady, Reginald; Rinker, Jennifer A; Nimitvilai, Sudarat et al. (2018) Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior. Handb Exp Pharmacol 248:311
Harlan, Benjamin A; Becker, Howard C; Woodward, John J et al. (2018) Opposing actions of CRF-R1 and CB1 receptors on VTA-GABAergic plasticity following chronic exposure to ethanol. Neuropsychopharmacology 43:2064-2074
Hanlon, Colleen A; Dowdle, Logan T; Henderson, J Scott (2018) Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. Pharmacol Rev 70:661-683
Hanlon, Colleen A; Dowdle, Logan T; Gibson, Nicole B et al. (2018) Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex. Transl Psychiatry 8:186
Gioia, Dominic A; Xu, Minfu; Wayman, Wesley N et al. (2018) Effects of drugs of abuse on channelrhodopsin-2 function. Neuropharmacology 135:316-327
Anton, Raymond F; Latham, Patricia K; Voronin, Konstantin E et al. (2018) Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence. Alcohol Clin Exp Res 42:751-760
Anderson, Ethan M; Larson, Erin B; Guzman, Daniel et al. (2018) Overexpression of the Histone Dimethyltransferase G9a in Nucleus Accumbens Shell Increases Cocaine Self-Administration, Stress-Induced Reinstatement, and Anxiety. J Neurosci 38:803-813
Osterndorff-Kahanek, Elizabeth A; Tiwari, Gayatri R; Lopez, Marcelo F et al. (2018) Long-term ethanol exposure: Temporal pattern of microRNA expression and associated mRNA gene networks in mouse brain. PLoS One 13:e0190841
Stewart, Scott H; Reuben, Adrian; Anton, Raymond F (2018) Reply: Carbohydrate Deficient Transferrin in Patients with Cirrhosis: A Tale of Bridges. Alcohol Alcohol 53:351-352

Showing the most recent 10 out of 209 publications