Paper

Virtual prototyping of non-invasive spinal cord electrical stimulation targeting upper limb motor function

Diaz-Pier, Sandra, Keesey, Rodolfo, Seáñez, Ismael, Cassoudesalle, Hélène, De Freitas, Roberto, Minassian, Karen, Gemar, Vincent, Milosevic, Matija, Neufeld, Esra, Wagner, Fabien, Rowald, Andreas, Hofstötter, Ursula, Hu, Zhaoshun, Sasaki, Atsushi, Brihmat, Nabila, Alashqar, Abdallah, Seong-Ryong Koh

2026

Overview

Transcutaneous spinal cord stimulation (tSCS) applied over the cervical or lumbar spinal cord facilitates motor function after paralysis. However, emerging electrophysiological evidence indicates mechanistic differences between cervical and lumbar tSCS and across different cervical tSCS paradigms. To clarify these discrepancies, we developed and validated a multi-scale, whole-body computational model of tSCS-induced volume conduction, axonal recruitment, and synaptic transmission. Across 24 cervical and four lumbar tSCS paradigms, simulations showed that somatosensory afferents consistently exhibit lower stimulation thresholds than motor efferents. In turn, region-specific synaptic transmission differences may explain electrophysiological discrepancies between cervical and lumbar tSCS. Across cervical tSCS paradigms, substantial volume conduction and axonal recruitment differences were observed that explain electrophysiological discrepancies. Specifically, clinically-prevalent paradigms, including those with anodes placed over the clavicles or iliac crests, engaged peripheral nerves in addition to spinal roots. This effect was amplified by multiphasic waveforms, which introduced recruitment sites near the anodes. By integrating simulations with electrophysiological recordings in 14 able-bodied individuals, we investigated previously unexplored cervical tSCS paradigms on their capacity to recruit somatosensory afferents relative to motor threshold.Competing Interest StatementA.R., F.W., K.M., E.N. hold several patents related to spinal cord stimulation. E.N. is minority shareholder and part-time employee of ZMT, which commercializes the Sim4Life platform.Funder Information DeclaredBundesministerium für Forschung, Technologie und Raumfahrt, 01ZZ2016Fondation pour la Recherche Médicale, https://ror.org/04w6kn183Institut pour la Recherche sur la Moelle Epinière et l'Encéphale, https://ror.org/04wsmmg28GPR inhibition programNational Institutes of Health, K01NS127936Personalized Health & Related Technologies

• Publisher: Cold Spring Harbor Laboratory Press
• Subject: Anodes / Conduction / Electrical stimuli / Nerve conduction / Paralysis / Peripheral nerves / Recruitment / Sensory neurons / Somatosensory system / Spinal cord / Synaptic transmission