Low-Intensity Pulsed Ultrasound Neuromodulation of the Hypoglossal Nerve for the Treatment of Sleep Apnea: An Animal Study
Thi-Thuyet Truong, Yi-Hsiang Chuang, Hsin Huang, Onanong Mee-Inta, Yu-Min Kuo, Jeng-Wen Chen, Wen-Tai Chiu, Chih-Chung Huang
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2026 · 10.1109/tnsre.2025.3640964
Abstract
Electrical stimulation of the hypoglossal nerve is an established therapy for obstructive sleep apnea, as activation of tongue muscles helps maintain airway patency during sleep. However, surgical implantation of electrodes carries inherent risks and limits broader application. In this study, we investigated a non-invasive approach using low-intensity pulsed ultrasound neuromodulation to stimulate the hypoglossal nerve and evaluated its effect on tongue muscle activity and upper-airway function. A 1-MHz ultrasound transducer was applied to the cervical region of anesthetized mice to deliver acoustic stimulation. Electromyography recordings from tongue muscles demonstrated that ultrasound effectively induced muscle activation via hypoglossal nerve neuromodulation. In addition, oxygen saturation and tongue displacement were monitored to assess functional improvements in upper-airway patency and to ensure safety with respect to tissue integrity and thermal effects. The results confirmed that ultrasound stimulation successfully modulated nerve activity and elicited tongue movements without evidence of tissue damage. These findings suggest that ultrasound-based neuromodulation offers a promising, safe, and non-invasive alternative for obstructive sleep disorder treatment.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS to hypoglossal nerve (US1 to US3)
Target: peripheral nerve — “hypoglossal nerve (HN)”
Device: Olympus / Panametrics · Olympus, Waltham, MA, USA · A314S ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 15, 60swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Ispta, domain unspecified (W/cm²) | 0.354, 0.51, 0.667swept | ✓✓✓⚑ |
Tone burst of 500 us, 50% duty cycle, PRF 1 kHz, applied at Ispta 354, 510 and 667 mW/cm2 (US1-US3) for 15-60 s until a response was observed, within non-stimulation, stimulation and post-stimulation phases.
Flags from extraction
exposures[0].unspecified_domain.ispta_w_cm2— Ispta values given without stating domain; hydrophone measurement in front of the transducer is described but not tied to these valuesexposures[0].timing.sonication_duration_s— 15-60 s 'until a response was observed'; the paper also notes up to 5 min continuous stimulation for temperature testsexposures[0].target— Hypoglossal nerve has no specific target id; mapped to peripheral_nerven_subjects— 18 mice aged 4-12 weeks stated; per-experiment numbers not given (at least three animals)