Topical Review: Electrophysiology equipment for reliable study of kHz electrical stimulation

Abstract

Characterizing the cellular targets of kHz (1–10 kHz) electrical stimulation remains a pressing topic in neuromodulation because expanding interest in clinical application of kHz stimulation has surpassed mechanistic understanding. The presumed cellular targets of brain stimulation do not respond to kHz frequencies according to conventional electrophysiology theory. Specifically, the low‐pass characteristics of cell membranes are predicted to render kHz stimulation inert, especially given the use of limited‐duty‐cycle biphasic pulses. Precisely because kHz frequencies are considered supra‐physiological, conventional instruments designed for neurophysiological studies such as stimulators, amplifiers, and recording microelectrodes do not operate reliably at these high rates. Moreover, for pulsed waveforms, the signal frequency content is well above the pulse repetition rate. Thus, the very tools used to characterize the effects of kHz electrical stimulation may themselves be confounding factors. We illustrate custom equipment design that supports reliable electrophysiological recording during kHz‐rate stimulation. Given the increased importance of kHz stimulation in clinical domains and compelling possibilities that mechanisms of actions may reflect yet undiscovered neurophysiological phenomena, attention to suitable performance of electrophysiological equipment is pivotal.

Signal filtering (attenuation) caused by electrophysiology devices. (A) Illustration of the performance of an isolator during kHz pulsed stimulation verified using a resistive, capacitive, or electrode (non‐linear) load and high precision ammeter and voltmeter. (B) represents amplifiers performance (in response to 1 mV sinusoidal input), and (C) shows experimental testing of attenuation with frequency by applying sinusoidal current to an experimental lead in a saline bath and measuring voltage. (D) Illustration of significant waveform distortion (below 100 kHz) from conventional stimulator and isolator, amplifier, and microelectrode (A, B, and C), which can only be corrected by a custom circuitry here.2

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