Phasic Neural Stimulation via Frequency-Modulated Kilohertz Signals: An Alternative to Amplitude Modulation
Kilohertz-frequency (kHz) electrical stimulation (1-100 kHz) is emerging as a powerful tool in both invasive and non-invasive neurostimulation applications, including functional electrical stimulation, spinal cord stimulation, and non-invasive brain stimulation. Most commonly these paradigms rely on amplitude modulation (AM-kHz)--achieved via burst or sinusoidal modulation--to produce phasic neural activation. Here, we propose, and validate, an alternative: frequency-modulated kilohertz stimulation (FM-kHz). This approach leverages the distinct strength-frequency dependence of kHz signals, whereby higher carrier frequencies are less efficient in depolarizing neurons than lower frequencies. By sweeping between sub- and suprathreshold frequencies, at a constant amplitude, FM-kHz generates a phasic neural activation envelope analogous to AM-kHz, without requiring amplitude modulation. Using both computational modelling and experimental data from Locusta migratoria (N5 nerve) and the human median nerve, we demonstrate that FM-kHz stimulation: 1. Produces reliable phasic evoked responses at the FM frequency; 2. Enables two degrees of control over stimulation--via FM frequency and frequency deviation. Across models tested, FM-kHz thresholds followed the same increasing strength-frequency relationship as AM-kHz, with FM-kHz requiring modestly higher thresholds at the upper end of the tested frequency range. These findings position FM-kHz as a viable and potentially advantageous alternative to AM-kHz strategies for future neuromodulation devices, and conceptually ground strength-frequency dependence as the key parameter in interpreting the effects of kHz electrical stimulation.