BACKGROUND: Peripheral nerve stimulation is used in both clinical and fundamental research for therapy and exploration. At present, non-invasive peripheral nerve stimulation still lacks the penetration depth to reach deep nerve targets and the stimulation focality to offer selectivity. It is therefore rarely employed as the primary selected nerve stimulation method. We have previously demonstrated that a new stimulation technique, temporal interference stimulation, can overcome depth and focality issues. METHODS: Here, we implement a novel form of temporal interference, bilateral temporal interference stimulation, for bilateral hypoglossal nerve stimulation in rodents and humans. Pairs of electrodes are placed alongside both hypoglossal nerves to stimulate them synchronously and thus decrease the stimulation amplitude required to activate hypoglossal-nerve-controlled tongue movement. RESULTS: Comparing bilateral temporal interference stimulation with unilateral temporal interference stimulation, we show that it can elicit the same behavioral and electrophysiological responses at a reduced stimulation amplitude. Traditional transcutaneous stimulation evokes no response with equivalent amplitudes of stimulation. CONCLUSIONS: During first-in-man studies, temporal interference stimulation was found to be well-tolerated, and to clinically reduce apnea-hypopnea events in a subgroup of female patients with obstructive sleep apnea. These results suggest a high clinical potential for the use of temporal interference in the treatment of obstructive sleep apnea and other diseases as a safe, effective, and patient-friendly approach. TRIAL REGISTRATION: The protocol was conducted with the agreement of the International Conference on Harmonisation Good Clinical Practice (ICH GCP), applicable United States Code of Federal Regulations (CFR) and followed the approved BRANY IRB File # 22-02-636-1279.

Central European Institute of Technology Brno University of Technology Brno 61200 Czech Republic

Department of Biomedical Engineering Linköping University Linköping 58185 Sweden

ENT and Allergy Associates 1500 Route 112 Port Jefferson Station New York 11776 USA

Institute de Neurosciences des Systèmes INSERM Aix Marseille Université Marseille 13005 France

International Clinical Research Center St Anne's University Hospital Brno Brno 60200 Czech Republic

IT'IS Foundation for Research on Information Technologies in Society Zurich 8004 Switzerland

Laboratory of Organic Electronics Linköping University Campus Norrköping Norrköping 602 21 Sweden

Somnial Inc 25 Health Sciences Dr Stony Brook New York USA

Bioelectron Med. 2024 Jan 24;10(1):5. doi: 10.1186/s42234-023-00139-w. PubMed

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