Title: Electromagnetic Field Modeling of Transcranial Electric and Magnetic Stimulation
Description: The proliferation of noninvasive transcranial electric and magnetic brain stimulation techniques and applications in recent years has led to important insights into brain function and pathophysiology of brain-based disorders. Transcranial electric and magnetic stimulation encompasses a wide spectrum of methods that have developed into therapeutic interventions for a variety of neurological and psychiatric disorders. Although these methods are at different stages of development, the physical principle underlying these techniques is the similar. Namely, an electromagnetic field is induced in the brain either via current injection through scalp electrodes or via electromagnetic induction. The induced electric field modulates the neuronal transmembrane potentials and, thereby, neuronal excitability or activity. Therefore, knowledge of the induced electric field distribution is key in the design and interpretation of basic research and clinical studies. This work aims to delineate the fundamental physical limitations, tradeoffs, and technological feasibility constraints associated with transcranial electric and magnetic stimulation, in order to inform the development of technologies that deliver safer, and more spatially, temporally, and patient specific stimulation.

Part I of this dissertation expounds on the issue of spatial targeting of the electric field. Contrasting electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) configurations that differ markedly in efficacy, side effects, and seizure induction efficiency could advance our understanding of the principles linking treatment parameters and therapeutic outcome and could provide a means of testing hypotheses of the mechanisms of therapeutic action. Using the finite element method, we systematically compare the electric field characteristics of existing forms of ECT and MST. We introduce a method of incorporating a modality-specific neural activation threshold in the electric field models that can inform dosage requirements in convulsive therapies. Our results indicate that the MST electric field is more focal and more confined to the superficial cortex compared to ECT. Further, the conventional ECT current amplitude is much higher than necessary for seizure induction. One of the factors important to clinical outcome is seizure expression.

However, it is unknown how the induced electric field is related to seizure onset and propagation. In this work, we explore the effect of the electric field distribution on the quantitative ictal electroencephalography and current source density in ECT and MST. We further demonstrate how the ECT electrode shape, size, spacing, and current can be manipulated to yield more precise control of the induced electric field. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Next, we demonstrate how the electric field induced by transcranial magnetic stimulation (TMS) can be controlled. We present the most comprehensive comparison of TMS coil electric field penetration and focality to date. The electric field distributions of more than 50 TMS coils were simulated. We show that TMS coils differ markedly in their electric field characteristics, but they all are subject to a consistent depth--focality tradeoff. Specifically, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electric field spread.

Figure-8 type coils are fundamentally more focal compared to circular type coils. Understanding the depth--focality tradeoff can help researchers and clinicians to appropriately select coils and interpret TMS studies. This work also enables the development of novel TMS coils with electronically switchable active and sham modes as well as for deep TMS. Design considerations of these coils are extensively discussed. Part II of the dissertation aims to quantify the effect of individual, sex, and age differences in head geometry and conductivity on the induced neural stimulation strength and focality of ECT and MST. Across and within ECT studies, there is marked unexplained variability in seizure threshold and clinical outcomes. It is not known to what extent the age and sex effects on seizure threshold are mediated by interindividual variation in neural excitability and/or anatomy of the head. Addressing this question, we examine the effect on ECT and MST induced field characteristics of the variability in head diameter, scalp and skull thicknesses and conductivities, as well as brain volume, in a range of values that are representative of the patient population.

Variations in the local tissue properties such as scalp and skull thickness and conductivity affect the existing ECT configurations more than MST. On the other hand, the existing MST coil configurations show greater sensitivity to head diameter variation compared to ECT. Due to the high focality of MST compared to ECT, the stimulated brain volume in MST is more sensitive to variation in tissue layer thicknesses. We further demonstrate how individualization of the stimulus pulse current amplitude, which is not presently done in ECT or MST, can be used as a means of compensating for interindividual anatomical variability, which could lead to better and more consistent clinical outcomes. Part III of the dissertation aims to systemically investigate, both computationally and experimentally, the safety of TMS and ECT in patients with a deep-brain stimulation system, and propose safety guidelines for the dual-device therapy. We showed that the induction of significant voltages in the subcutaneous leads in the scalp during TMS could result in unintended and potentially dangerous levels of electrical currents in the DBS electrode contacts.

When applying ECT in patients with intracranial implants, we showed that there is an increase in the electric field strength in the brain due to conduction through the burr holes, especially when the burr holes are not fitted with nonconductive caps. Safety concerns presently limit the access of patients with intracranial electronic devices to therapies involving transcranial stimulation technology, which may preclude them from obtaining appropriate medical treatments. Gaining better understanding of the interactions between transcranial and implanted stimulation devices will demarcate significant safety risks from benign interactions, and will provide recommendations for reducing risk, thus enhancing the patient's therapeutic options.