Auricular Ultrasonic Vagus Nerve Stimulation: Effectiveness of Blinding and the Occurrence of Adverse Effects in People with Tinnitus
Poppy Hinton, Bas Labree, Marcus Kaiser, Mohamad A. Pourhoseingholi, Magdalena Sereda
Brain Sciences 2026 · 10.3390/brainsci16060586
Abstract
Background/Objectives : Vagus Nerve Stimulation (VNS) has been suggested as a treatment for tinnitus, but its effect on the condition remains unclear. Ultrasonic Vagus Nerve Stimulation (U-VNS) involves non-invasive stimulation of the auricular branch of the vagus nerve, potentially providing an alternative to traditional VNS. To pre-emptively address some of the methodological challenges of future trials investigating U-VNS, a highly blindable sham device is needed. This study aimed to (1) investigate the effectiveness of blinding of a U-VNS device and (2) record any adverse effects, including any negative effects on tinnitus loudness, alongside their onset and duration. Methods : In this single-blind randomized controlled study, 20 volunteers with chronic tinnitus received two 29 min sessions of true U-VNS followed by sham U-VNS, or vice versa. Sessions were a week apart, and in a randomized order. The effectiveness of blinding and adverse effects, including changes in tinnitus loudness, were measured using self-report questionnaires. Results : James' Blinding Index revealed that blinding was highly effective in both the real U-VNS condition, BI = 0.79, 95% CI (0.61-0.92), and the sham condition, BI = 0.76, 95% CI (0.60-0.89). Adverse effects were uncommon and mild, primarily consisting of sensations on the skin beneath the transducer. For most participants, tinnitus loudness either decreased or stayed the same in both conditions. Conclusions : A high level of blinding was achieved, suggesting that the ZenBud sham device may be suitable as an effective placebo control in future trials. Adverse effects were uncommon and mild. These findings will help inform the design of future clinical trials to evaluate the safety and efficacy of U-VNS.
Abstract via europepmc.
Exposures
Exposure 1: Active U-VNS via ZenBud device to the auricular branch of the vagus nerve
Target: vagus nerve — “auricular branch of the vagus nerve”
Device: other named manufacturer · NeurGear Inc. · ZenBud ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 5,300 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 12.1951 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 41 | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 1,740 | ✓✓✓ |
| 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 | |
| Pressure, domain unspecified (kPa) | 1,030 | ✓✓✓⚑ |
The device turns off automatically after 29 min, and is designed to imitate a standard headset. Participants underwent either active U-VNS or sham stimulation using the ZenBud device, which lasted for approximately 29 min, during which time they sat in a quiet room with the investigator.
Flags from extraction
exposures[0].unspecified_domain.pressure_kpa— Paper calls this value an 'average intensity' but reports it in MPa (a pressure unit) rather than W/cm²; recorded as pressure since the unit is a pressure unit. Domain (free field vs in situ) is not stated.exposures[0].timing.pulse_duration_ms— PRF (41 Hz) and duty cycle (50%) are stated but no pulse duration is given in the text, so pulse duration is left not_reported rather than computed.blinding— Only participants were blinded; investigator blinding was not possible because the active and sham transducers sat on different ears.