Waveform-based modulation of non-invasive peripheral nerve stimulation

Abstract

Electromagnetic peripheral nerve stimulation (PNS) has many wide-reaching diagnostic and therapeutic applications ranging from assessment of nerve injury to rehabilitation therapy and pain management. Non-invasive electrical stimulation techniques using surface electrodes are preferred when possible. However, due to the highly spatially local fields produced by electrode-to-electrode current flow, deeper stimulation targets such as spinal cord, nerve roots, and ganglia currently require surgically implanted electrodes. In magnetostimulation, the electric field is induced by the time-varying magnetic field which penetrates the body, enabling non-invasive stimulation at depth. While magnetostimulation of nerves in magnetic resonance imaging should be avoided to ensure patient comfort and safety, magnetostimulation is the primary mechanism of action in non-invasive transcranial magnetic stimulation and has been reported to have benefits over traditional electrical peripheral nerve stimulation. The induced electric field is highly shaped by the body and so generating targeted, specific magnetostimulation requires an in depth understanding of the dynamics of the electric potential across the axon membrane through complex mechanisms including charge build up at the axon’s membrane and charge redistribution along the axon over time. This motivates the need for detailed analysis of how temporal modulation of the waveform including the application of multiple frequency waveforms might alter the nerve membrane state and its excitation threshold.

In this dissertation I characterize magnetostimualtion axon excitability as a function of stimulus waveform, present experimental high frequency stimulation thresholds, and propose waveform-based methods to exploit the biophysical properties of axons and reduce excitation. This work shows that a deeper understanding of axonal excitation can lead to informed waveform design and better control of magnetostimulation. This work may be useful in MRI where the detailed knowledge of anatomy and electric field induction can be used to prevent stimulation and also in clinical neurostimulation where better understanding of excitation may enable increased targeting and neuromodulation.