Date of Award

1-1-2022

Embargo Period

4-22-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

College

College of Graduate Studies

First Advisor

Colleen A. Hanlon

Second Advisor

Jens H. Jensen

Third Advisor

Mark S. George

Fourth Advisor

Lisa M. McTeague

Fifth Advisor

Jennifer A. Rinker

Sixth Advisor

Carmela M. Reichel

Abstract

Alcohol Use Disorder (AUD) is the third leading cause of preventable death in the United States. While there are several treatment options available, none of these interventions specifically target the neural circuits known to contribute to alcohol use, abstinence, and relapse. In the following chapters, this dissertation will introduce transcranial magnetic stimulation (TMS) as a potential neural-circuit based therapeutic tool for AUD. Following a brief introduction to the neural circuitry involved in AUD (Chapter 1), Chapter 2 reviews the results of a multimodal randomized, double-blind, sham-controlled trial evaluating 10 sessions of TMS delivered to the frontal pole as a therapeutic tool for AUD. In this study, active TMS significantly reduced brain reactivity to alcohol cues and improved 3-month sobriety rates relative to sham, however there was high degree of individual variability in response to treatment. To explore neurobiological sources of variability that may influence TMS efficacy, Chapters 3 and 4 address three unique aspects of brain structure in AUD: grey and white matter integrity (Chapter 3) and scalp-to-cortex distance (Chapter 4). Chapter 3 demonstrates that individuals with AUD have lower cortical grey and white matter volume in areas frequently targeted with TMS, suggesting a greater dose of TMS may be needed to modulate cortical-striatal circuits. Chapter 4 demonstrates that while scalp-to-cortex distances (and TMS induced electric fields) are not significantly different between individuals with AUD and controls, overall, males have a longer scalp-to-cortex distance than females. This suggests that men may need a higher intensity of stimulation to achieve a comparable electric field strength at the cortex. Following the observations from Chapters 3 and 4, we conclude with a secondary analysis of Chapter 2. Additionally, we explore the influence of individual patterns of brain reactivity to alcohol cues as a factor associated with treatment response. The results demonstrated that individuals with overlapping electrical field and patterns of brain reactivity to alcohol cues were significantly more likely to remain sober at 3 months. Collectively, these findings provide strong evidence that TMS is an effective treatment for AUD and that integrating individual brain function and structure may robustly enhance treatment response.

Rights

All rights reserved. Copyright is held by the author.

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