Obstructive Sleep Apnea Improves with Non‑invasive Hypoglossal Nerve Stimulation Using Temporal Interference

Florian Missey, Malin Silverå Ejneby, Ibrahima Ngom, Mary J. Donahue, Jan Trajlinek, Emma Acerbo, Boris Botzanowski, Antonino M. Cassarà, Esra Neufeld, Eric D. Glowacki, Lee Shangold, William M. Hanes and Adam Williamson, Bioelectronic Medicine 2023, Volume 9, Article No. 18, online 09 August 2023; doi: 10.1186/s42234-023-00120-7

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 (TI) stimulation, can overcome depth and focality issues. In this research work, we implement a novel form of TI, bilateral TI 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. Comparing results from bilateral TI stimulation with unilateral TI 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. During this first-in-man studies, TI 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 TI in the treatment of obstructive sleep apnea and other diseases as a safe, effective, and patient-friendly approach.

The scientific and technical impact of the study can be summarized as:

• This study is one of the first to demonstrate the successful application of the TI concept for peripheral nerve stimulation
• The results indicate the promising potential of TI stimulation as a non-invasive means of treating sleep apnea
• In silico modeling proved valuable in assessing and optimizing the exposure and experimental design