Auricular Ultrasonic Vagus Nerve Stimulation: Effectiveness of Blinding and Occurrence of Adverse Effects in Healthy Volunteers
Bas Labree, Marcus Kaiser, Mohamad A. Pourhoseingholi, Derek J. Hoare, Magdalena Sereda
Brain Sciences 2025 · 10.3390/brainsci15090986
Abstract
Background/objectives Both invasive and non-invasive electrical stimulation of the vagus nerve have been studied as potential treatments for neurological conditions, with mixed results. Ultrasonic Vagus Nerve Stimulation (U-VNS), which non-invasively stimulates the auricular branch of the vagus nerve using ultrasound, may offer a more targeted and effective approach than electric currents. To facilitate future clinical trials of U-VNS, this study aimed to (1) investigate the effectiveness of blinding of a U-VNS device versus a sham device and (2) record the type, onset, and duration of any adverse effects resulting from U-VNS. Methods In this single-blind randomised controlled study, twenty healthy volunteers were randomly assigned to receive either a 30 min session of true U-VNS and a 30 min session of sham stimulation 1 week later, or vice versa. The effectiveness of blinding and the occurrence of adverse effects were measured using self-report questionnaires. Results James' Blinding Index showed that blinding using the sham device was highly effective in both the real U-VNS condition, BI = 0.9 (95% CI: 0.7-1.0), and the sham condition, BI = 1.0 (95% CI: 1.0-1.0). The adverse effects reported were mild, transient, and mostly related to sensations on the skin immediately under the transducer of the device. Conclusions A high level of blinding effectiveness can be achieved for U-VNS by using a sham device. Adverse effects are generally mild and transient. These findings will inform the design of future clinical trials of U-VNS.
Abstract via europepmc.
Exposures
Exposure 1: Real ultrasonic vagus nerve stimulation (U-VNS) via ZenBud device
Target: vagus nerve — “auricular branch of the vagus nerve”
Device: other named manufacturer · NeurGear · 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 | ✓✓✓⚑ |
It delivers low-intensity focused ultrasound to the auricular branch of the vagus nerve through several layers of skin (centre frequency 5.3 MHz, pulse repetition rate 41 hertz, 50% duty cycle, average intensity of 1.03 MPa). As a safety measure, the device shuts down automatically after running for 29 min. Participants sat in a quiet room with an investigator whilst undergoing stimulation (or sham) using the ZenBud device for 29 min; the abstract describes this as a '30 min session'.
Flags from extraction
exposures[0].unspecified_domain.pressure_kpa— The paper labels this value 'average intensity of 1.03 MPa', but MPa is a pressure unit not an intensity unit; recorded as a pressure (1030 kPa) since the stated units are MPa. Domain (free-field vs in-situ) is not specified by the paper, so placed in unspecified_domain.exposures[0].timing.sonication_duration_s— Abstract states sessions were '30 min', but the Methods/Procedure and device description both state the device runs for 29 min and auto-shuts-off after 29 min; 29 min (1740 s) used as the more specific/detailed value, with the discrepancy flagged.exposures[0].timing.pulse_duration_ms— PRF (41 Hz) and duty cycle (50%) are both stated, which could allow pulse duration to be computed, but the paper does not state pulse duration directly, so left not_reported per the no-arithmetic rule.readouts— This study assessed only blinding effectiveness and adverse effects via questionnaires, not a physiological or behavioural effect of stimulation, hence classified as none_reported.