Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.

Bioelectronics Materials and Devices Lab Central European Institute of Technology Brno University of Technology Purkyňova 123 Brno 61200 Czech Republic

EMUNE AB Nanna Svartz väg 6A Solna 171 65 Sweden

Foundation for Research on Information Technologies in Society Zeughaustrasse 43 Zurich 8004 Switzerland

Institut de Neurosciences des Systèmes INSERM UMR_1106 Aix Marseille Université Marseille France

Laboratory of Immunobiology Center for Bioelectronic Medicine Department of Medicine Solna Karolinska Institutet Stockholm Sweden

Laboratory of Organic Electronics Campus Norrköping Linköping University Norrköping Sweden

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