Date of Award

Spring 5-20-2023

Embargo Period

5-20-2028

Document Type

Dissertation - MUSC Only

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

First Advisor

Mark S. George

Second Advisor

Jeffrey J. Borckardt

Third Advisor

Jens H. Hensen

Fourth Advisor

Lisa M. McTeague

Fifth Advisor

Nathan C. Rowland

Abstract

Noninvasive brain stimulation, including transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), can effectively treat numerous psychiatric and neurological diagnoses, including depression, tobacco use disorder, obsessive compulsive disorder, and migraine headaches. However, despite FDA-approval for multiple TMS treatments, many patients still fail to respond to treatment. In addition, while tES is a promising technology, there are no FDA-approved treatments to date. In TMS and tES, developing more personalized and optimized dosing to ensure that each patient receives sufficient target engagement of the intended brain region could lead to higher and more consistent response rates across patients and diagnoses.

This dissertation is comprised of 10 studies exploring the utility of electric field (E-field) modeling to personalize and optimize stimulation approaches transdiagnostically using TMS and tES. E-field modeling accurately estimates the stimulation intensity at the cortical target using current flow models with experimentally derived tissue conductivity values. The present work includes the development of prospective E-field based dosing approaches, technical refinement of modeling methodology, and the use of E-field modeling to strategically derive novel tES electrode positioning that maximizes on-target stimulation intensity while minimizing off-target effects.

Regarding TMS, we found that the standard clinically applied 120% motor threshold intensity over the prefrontal cortex is insufficient to produce the same E-fields elicited over the motor cortex and with high inter-individual variability. In tES, one-size-fits-all 2mA stimulation produced a wide range of individual cortical stimulation intensities, and reverse-calculation E-field dosing can reduce the variability over 100x. The cortical intensity at the brain target is behaviorally meaningful, with older adult participants having significantly larger working memory improvements when they experienced higher E-fields from 2mA. Utilizing E-field modeling to derive novel tES electrode placement strategies in 3000 models, we found that smaller electrodes placed equidistant and surrounding the cortical target produces over double the on-target E-field as traditional approaches with a fraction of the off-target effects. Finally, our research has begun to address the technical hurdles necessary to implement prospective personalized E-field dosing. Using T1 and T2-weighted scans maximizes model accuracy, and outcome measure selection critically impacts modeling results, such that the average volume overlap between common outcome measure methods is only 6%.

In sum, E-field modeling is a useful approach to personalize and optimize TMS and tES. With the reverse-calculation dosing approach, data suggestive of a positive dose-response curve, and standardization of MR scan type and outcome measure selection between studies, future experiments can begin to test the therapeutic utility of individualizing E-field dosing prospectively.

Rights

Copyright is held by the author. All rights reserved.

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Available for download on Saturday, May 20, 2028

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