Robert J. Butera, Ph.D. (Georgia Institute of Technology, School of ECE and Dept. of BME)
Laura O’Farrell, DVM, Ph.D. (Georgia Institute of Technology, GTRC)
Arthur English, Ph.D. (Emory University, Dept. of Cell Biology)
Chris Rozell, Ph.D. (Georgia Institute of Technology, School of ECE)
Thomas Burkholder, Ph.D. (Georgia Institute of Technology, School of Applied Physiology)
Optimization and Application of Kilohertz Electrical Stimulation to Autonomic Neural Circuits
More than half a century after the first implantation of a cardiac pacemaker (1958), there is a renewed interest in the ability to electrically stimulate biological tissues, specifically peripheral nerves, to relieve clinical conditions. In their most common form, these implanted devices deliver brief bursts of electrical pulses at various frequencies (< 130 Hz) to peripheral nerves, the spinal cord, or the brain to activate nearby excitable tissues. By doing so, these therapies treat symptoms related to disorders such as epilepsy, depression, and obesity. In stark contrast to this burst of neural activation induced by low frequency stimulation is the ability to completely inhibit neural activity using continuous, kilohertz frequency electrical stimulation. When applied to peripheral nerves, kilohertz electrical stimulation creates a localized block of peripheral nerve activity, thus inhibiting propagation of activity between neural elements (e.g., ganglia, spinal circuits, the brain) and end-targets (e.g., organs, muscles).
Although implemented in a handful of clinical devices, a significant number of parameters remain to be investigated for achieving a safe and effective nerve block using kilohertz electrical stimulation. Furthermore, the application of kilohertz electrical stimulation to block propagating activity in autonomic neural circuits, specifically as it relates to maintaining homeostasis, remains an uncharted territory. The goal of this thesis was thus two-fold - i) optimize kilohertz electrical stimulation parameters for safe and effective clinical implementation and ii) investigate the utility of kilohertz electrical stimulation nerve block in autonomic neural circuits involved in homeostatic regulation.
In the first part, I briefly discuss optimized electrode geometries that increase the battery life of implanted devices, as well as the electrochemical behavior of electrodes at kilohertz frequencies. In the second part, I discuss application of kilohertz electrical stimulation nerve block to autonomic neural circuits involved in regulation of systemic inflammation and glycemia. I demonstrate the therapeutic benefits of inhibiting nerve activity in each physiological circuit and discuss potential mechanisms underlying the observed therapeutic benefits.
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Meeting ID: 291990472