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

Area of Science:

• Neuroscience
• Biomedical Engineering
• Electrical Engineering

Background:

• Kilohertz frequency (KHF) electrical stimulation shows promise for treating diseases by blocking peripheral nerve conduction.
• Previous research utilized various KHF waveforms, but their specific impact on nerve block parameters remains unclear.

Purpose of the Study:

• To quantify how different KHF electrical waveforms affect nerve block thresholds and onset responses.
• To compare the efficacy of sinusoidal and rectangular waveforms in blocking nerve conduction in vivo and in silico.

Main Methods:

• In vivo experiments on rat tibial nerves and computational modeling were used to compare block thresholds and onset responses.
• Current-controlled sinusoidal and charge-balanced rectangular waveforms with varying duty cycles and asymmetries were tested.

Main Results:

• Sine waves exhibited higher block thresholds than square waves but required less power. Rectangular waveform block thresholds inversely correlated with duty cycle.
• Computational models aligned with in vivo findings, though they underestimated duty cycle effects. Axonal membrane filtering resulted in similar post-filtered RMS block thresholds across waveforms.
• Onset response was less affected by waveform shape but decreased at higher amplitudes and with repeated trials.

Conclusions:

• Waveform significantly influences nerve block thresholds, while amplitude relative to threshold impacts onset response.
• These findings guide waveform selection for KHF neurostimulation in research and clinical settings.
• Optimizing waveform parameters can enhance therapeutic efficacy and minimize undesirable onset responses.