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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA010761-23
Application #
9404940
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
23
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
Laguesse, Sophie; Morisot, Nadege; Shin, Jung Hoon et al. (2017) Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward. Neuron 96:145-159.e8
Cannady, Reginald; McGonigal, Justin T; Newsom, Ryan J et al. (2017) Prefrontal Cortex KCa2 Channels Regulate mGlu5-Dependent Plasticity and Extinction of Alcohol-Seeking Behavior. J Neurosci 37:4359-4369
Anderson, Rachel I; Becker, Howard C (2017) Role of the Dynorphin/Kappa Opioid Receptor System in the Motivational Effects of Ethanol. Alcohol Clin Exp Res 41:1402-1418
Witkiewitz, Katie; Wilson, Adam D; Pearson, Matthew R et al. (2017) Temporal Stability of Heavy Drinking Days and Drinking Reductions Among Heavy Drinkers in the COMBINE Study. Alcohol Clin Exp Res 41:1054-1062
Litten, Raye Z; Falk, Daniel E; O'Malley, Stephanie S et al. (2017) Letter to Editor in Response to Johnson's Commentary (2017) on the Witkiewitz and Colleagues (2017) Article. Alcohol Clin Exp Res 41:1381-1382
Rinker, Jennifer A; Fulmer, Diana B; Trantham-Davidson, Heather et al. (2017) Differential potassium channel gene regulation in BXD mice reveals novel targets for pharmacogenetic therapies to reduce heavy alcohol drinking. Alcohol 58:33-45
Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J et al. (2017) Ethanol Dependence Abolishes Monoamine and GIRK (Kir3) Channel Inhibition of Orbitofrontal Cortex Excitability. Neuropsychopharmacology 42:1800-1812
Trantham-Davidson, Heather; Centanni, Samuel W; Garr, S Corrin et al. (2017) Binge-Like Alcohol Exposure During Adolescence Disrupts Dopaminergic Neurotransmission in the Adult Prelimbic Cortex. Neuropsychopharmacology 42:1024-1036
Rinker, Jennifer A; Mulholland, Patrick J (2017) Promising pharmacogenetic targets for treating alcohol use disorder: evidence from preclinical models. Pharmacogenomics 18:555-570
Stewart, Scott H; Reuben, Adrian; Anton, Raymond F (2017) Relationship of Abnormal Chromatographic Pattern for Carbohydrate-Deficient Transferrin with Severe Liver Disease. Alcohol Alcohol 52:24-28

Showing the most recent 10 out of 179 publications