SPARC: Effect of Waveform on Kilohertz Frequency Nerve Block

Abstract

There is growing interest in delivering kilohertz frequency (KHF) electrical signals to block conduction in autonomic nerves as a therapy to treat various diseases. Previous computational modeling, preclinical, and clinical studies used multiple different KHF waveforms to achieve block of the sciatic, vagus, and pudendal nerves. However, it remains unclear how the choice of waveform affects clinically relevant nerve block parameters. To address this knowledge gap, we quantified the effects of waveform on KHF block in vivo for the rat sciatic nerve, as well as in computational models of the rat sciatic nerve and the human vagus nerve. We compared block thresholds and onset responses across KHF sinusoids and charge‐balanced rectangular waveforms with different symmetries and duty cycles.Block thresholds were strongly dependent on the waveform shape. Experimentally, symmetric rectangular waveforms with full duty cycles had lower current thresholds for block than sinusoids, but they used slightly more power at threshold. Further, lower duty cycles yielded higher block thresholds, such that the log‐transformed block thresholds increased in an approximately linear manner as duty cycle decreased. The results from computational models were consistent with the in vivo block threshold relationships, although the models underestimated the increase in threshold with decreased duty cycle.While waveform selection had a clear and distinct effect on thresholds, it did not consistently affect in vivo onset response. Onset magnitude was similar across waveforms when normalized to block threshold. We also observed a history‐dependent reduction in onset response across all waveforms, from earlier trials with larger onset responses to later trials with reduced onsets during the course of a given experiment.Waveform had substantial effects on block thresholds but not on onset response. These quantitative data inform choice of waveform in subsequent studies and clinical applications. Such an understanding of the direct effects of KHF signal parameters on neural activity will enhance its effective use in therapeutic applications and facilitate the design of KHF stimulation parameters that achieve block with minimal undesired onset responses.Support or Funding InformationNIH SPARC OT2 OD025340