Optimization and application of kilohertz electrical stimulation nerve block to autonomic neural circuits

Abstract

Kilohertz Electrical Stimulation (KES) enables a rapid, reversible, and localized inhibition of peripheral nerve activity. Discovered in the early 1900’s, the utility and application of KES nerve block to treat symptoms of various disease states is nearly non-existent. Although a handful of clinical products utilize KES, it is highly debated and unknown if these products provide therapeutic benefit or, if they do, whether they do it by achieving a true conduction block of nerve activity or through other unknown mechanisms of action. Furthermore, many critical questions still re- main about the optimal electrodes, waveforms, and approaches necessary for clinical utility of KES nerve conduction block. In this thesis, I investigate multiple facets of KES nerve conduction block. In Part I, I present electrode optimizations that reduce energy requirements and ensure optimal KES nerve conduction block. I de- scribe critical geometry and materials considerations for electrode design, quantify charge characteristics of KES waveforms, and discuss how electrode characteristics can impact clinical device design. In Part II, I demonstrate the utility of KES in a variety of somatosensory and autonomic neural circuits to treat symptoms arising from immune and metabolic disorders. I show that KES nerve block can selectively block conduction in different fiber-types for selective inhibition of motor and sensory information. I then demonstrate the ability of KES nerve block to provide direction- specific stimulation of the vagus nerve for modulation of the innate immune system. Finally, I demonstrate the utility of KES nerve block for modulation of glucose metabolism. Collectively, the methods, tools, and results presented in this thesis significantly impact the design and clinical translation of KES therapies.