Quantitative comparisons of block thresholds and onset responses for charge-balanced kilohertz frequency waveforms

Abstract

Objective. There is growing interest in delivering kilohertz frequency (KHF) electrical signals to block conduction in peripheral nerves for treatment of various diseases. Previous studies used different KHF waveforms to achieve block, and it remains unclear how waveform affects nerve block parameters. Approach. We quantified the effects of waveform on KHF block of the rat tibial nerve in vivo and in computational models. We compared block thresholds and onset responses across current-controlled sinusoids and charge-balanced rectangular waveforms with different asymmetries and duty cycles. Main results. Sine waves had higher block thresholds than square waves, but used less power at block threshold. Block threshold had an inverse relationship with duty cycle of rectangular waveforms irrespective of waveform asymmetry. Computational model results were consistent with relationships measured in vivo, although the models underestimated the effect of duty cycle on increasing thresholds. The axonal membrane substantially filtered waveforms, the filter transfer function was strikingly similar across waveforms, and filtering resulted in post-filtered rms block thresholds that were approximately constant across waveforms in silico and in vivo. Onset response was not consistently affected by waveform shape, but onset response was smaller at amplitudes well above block threshold. Therefore, waveforms with lower block thresholds (e.g. sine waves or square waves) could be more readily increased to higher amplitudes relative to block threshold to reduce onset response. We also observed a reduction in onset responses across consecutive trials after initial application of supra-block threshold amplitudes. Significance. Waveform had substantial effects on block thresholds, and the amplitude relative to block threshold had substantial effects on onset response. These data inform choice of waveform in subsequent studies and clinical applications, enhance effective use of block in therapeutic applications, and facilitate the design of parameters that achieve block with minimal onset responses.