Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS) offers great potential as a noninvasive neuromodulation technique with expanding therapeutic potential across a range of neurological and systemic indications. Yet despite strong clinical interest, the mechanistic foundations of taVNS remain incompletely understood. In contrast to the invasive form of vagus nerve stimulation (VNS), taVNS has seen more limited parametric characterization, with many studies relying on parameters adopted from invasive protocols without systematic validation at the noninvasive level. This dissertation focuses on developing a more comprehensive understanding of the underlying mechanisms of taVNS. It extends existing literature by leveraging intracranial electrophysiology to directly quantify neural responses to both traditional electrical taVNS and a novel vibrotactile modality. Furthermore, it broadens the scope of mechanistic research to consider the central nervous system in its entirety by probing responses in spinal motoneuron excitability. Using stereotactic electroencephalography (sEEG), we first investigated local activity in deep brain regions across a range of stimulation intensities. We observed increased gamma power during 1.0 and 1.5 mA active taVNS in several limbic regions, predominantly concentrated in the left hemisphere. Additionally, we observed that this increased gamma power was sustained throughout the duration of stimulation in both the insula and orbitofrontal cortex (OFC). Notably, lower intensity stimulation (0.5 mA) resulted in a subtle decrease in gamma power in some regions. These contrasting, amplitude-specific responses provide rationale for the critical role parameter selection plays in the efficacy of neuromodulation and may partially explain the variability of results present in VNS and taVNS literature. To establish a more generalizable method of noninvasive vagal activation, we next designed and built a custom earpiece intended to stimulate the cymba concha mechanically via vibration. We again used sEEG recordings to investigate brain responses across five vibration frequencies, observing significant increases in global low-frequency coherence during 6, 20, and 40 Hz stimulation. These findings support the use of vibrotactile stimulation as a viable alternative modality for noninvasive VNS, motivating further investigation into behavioral, clinical, and sham-controlled mechanistic studies. Finally, to complement the two studies focusing on brain responses to taVNS, we also investigated the role of spinal circuits, and more specifically spinal motoneuron excitability, in mediating the effects of taVNS. Addressing a notable gap in the literature, we designed a protocol using evoked electromyography (EMG) to measure changes in motoneuron excitability in healthy individuals during concurrent taVNS. In this pilot study, we did not observe significant changes in motoneuron excitability, quantified via F-wave persistence and amplitude, across either active taVNS or sham stimulation. However, notable individual variability suggests that a larger sample size may reveal more subtle or context-dependent spinal effects. Collectively, this dissertation reveals the nuanced interactions between taVNS and the central nervous system, underscoring the need for continued mechanistic research. Careful optimization of stimulation parameters – including intensity and modality – will be essential for realizing the full therapeutic potential of taVNS.

Committee Chair

Eric Leuthardt

Committee Members

Benjamin Philip; Daniel Moran; Ismael Seáñez; Peter Brunner

Degree

Doctor of Philosophy (PhD)

Author's Department

Biomedical Engineering

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

8-18-2025

Language

English (en)

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Available for download on Saturday, August 15, 2026

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