Fundamental limitations of kilohertz-frequency carriers in afferent fibre recruitment with transcutaneous spinal cord stimulation.

Kilohertz-frequency (KHF) waveforms are gaining traction in transcutaneous spinal cord stimulation (tSCS) for motor recovery after paralysis. However, the mechanisms by which these fast-alternating currents depolarize proprioceptive afferent and motor efferent fibres remain unknown. To address this gap, we conducted a study in 28 participants showing, through peripheral nerve stimulation experiments and computational modelling, that KHF waveforms negatively impact the processes required to electrically induce action potentials, thereby increasing response thresholds and biasing recruitment towards motor efferent fibres. While these results translate to tSCS, we also demonstrate that lumbar tSCS still results in the preferential recruitment of proprioceptive afferent fibres, whereas cervical tSCS favours recruitment of motor efferent fibres, regardless of the waveform used. Given the assumed importance of proprioceptive afferent stimulation in motor recovery, our work suggests that the use of KHF waveforms warrants careful consideration in the context of neurorehabilitation applications, particularly for cervical tSCS. We posit that a thorough analysis of the mechanisms mediating responses elicited by novel tSCS approaches is crucial for understanding their potential to restore motor function after paralysis.