With advances in opto-/chemo-genetic stimulation techniques, preclinical studies have demonstrated that activity in frontal-striatal neural circuits has a causal influence on heavy alcohol drinking and relapse-like behavior. Similar findings using modern fMRI imaging techniques in humans have confirmed some of these findings. Clinically, however, we have not yet translated this research into a neural circuit based therapeutic technique for patients with alcohol use disorder (AUD). The long term goal of our multidisciplinary research team is to determine the optimal parameters through which non-invasive transcranial magnetic stimulation (TMS) can be used to improve alcohol drinking outcomes (abstinence, heavy drinking days) among individuals seeking behavioral treatment for AUD. Building on a foundation of several TMS brain target identification studies and a small double-blinded clinical trial in treatment-engaged AUD patients performed by our group in the Charleston Alcohol Research Center (ARC), here we propose a double-blind placebo controlled, randomized study to evaluate the efficacy of theta burst stimulation (TBS) to ventromedial prefrontal cortex (vmPFC) as a treatment to decrease drinking and brain reactivity to alcohol cues among treatment-seeking individuals with AUD. Individuals will be screened initially by the ARC Clinical Intake and Assessment Core, then given an opportunity to enroll in this study, provide informed consent, and be randomized to receive real or sham TBS to the vmPFC 36 sessions (3x/day on each of 3 days/week over 4 weeks, i.e., 12 days). Prior to randomization and again after 4 weeks of TBS treatment, they will receive a well-established and validated alcohol-cue stimulation BOLD fMRI procedure. The scientific premise of this ARC research proposal is that, by modulating the neural circuits that regulate alcohol cue-reactivity, it will be possible to increase alcohol abstinence rates and decrease heavy drinking days over a 4-month period. Accordingly, we will explore the relationship of TBS-induced changes in brain reactivity to alcohol cues as mediators of the TBS treatment response. Also, brain activation to natural reward and threat cues will be studies as a means to probe potential effects of TBS treatment on negative affect/emotionality associated with AUD. With our combined scientific expertise in brain stimulation, neuroimaging, clinical (and preclinical) alcohol-related research in the Charleston ARC, and AUD clinical trial expertise, MUSC is uniquely suited to develop this critical line of research. The outcomes of the proposed Aims will provide an evidence-based foundation for a multisite clinical trial and will hasten progress towards developing a new neural circuit-based treatment for individuals with AUD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
2P50AA010761-26
Application #
10055949
Study Section
Special Emphasis Panel (ZAA1)
Project Start
1996-12-01
Project End
2025-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
26
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29407
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
Kearney-Ramos, Tonisha E; Lench, Daniel H; Hoffman, Michaela et al. (2018) Gray and white matter integrity influence TMS signal propagation: a multimodal evaluation in cocaine-dependent individuals. Sci Rep 8:3253
Haun, Harold L; Griffin, William C; Lopez, Marcelo F et al. (2018) Increasing Brain-Derived Neurotrophic Factor (BDNF) in medial prefrontal cortex selectively reduces excessive drinking in ethanol dependent mice. Neuropharmacology 140:35-42
Schacht, Joseph P; Voronin, Konstantin E; Randall, Patrick K et al. (2018) Dopaminergic Genetic Variation Influences Aripiprazole Effects on Alcohol Self-Administration and the Neural Response to Alcohol Cues in a Randomized Trial. Neuropsychopharmacology 43:1247-1256

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