Quantifying the Effects of Kilohertz Frequency Electrical Signals on Small Autonomic Nerve Fibers: Computational Modeling and In Vivo Electrophysiology AKA Applying Fast Signals to Slow Nerves

There is growing interest in treating diseases through electrical stimulation and block of peripheral autonomic nerves, especially the vagus nerve (VN). Applications include treatment of epilepsy, depression, obesity, heart failure, rheumatoid arthritis, and Crohn’s disease. Development of these neuromodulation therapies requires understanding the excitation properties of the small myelinated and unmyelinated autonomic fibers that constitute the VN. Further, effective neuromodulatory therapies require the capability to block unwanted neural activity, as well as the ability to generate controlled activation. The studies herein quantify autonomic axon responses to conventional pulse stimulation and to kilohertz frequency (KHF) signals, which can produce neural conduction block. Through this examination of axonal responses to a range of electrical signals, we strengthen the foundation upon which neuromodulatory therapies are built.