Effects of Very Low-Intensity Transcranial Ultrasound Stimulation on Corticospinal Excitability and Motor Performance in Healthy Individuals
Minoru Motoyama, Tomofumi Yamaguchi, Mizuki Hamasuna, Kotaro Kawashima, Natsuki Katagiri, Shigeo Tanabe, Shuhei Shibukawa, Toshiyuki Fujiwara
Ultrasound in Medicine & Biology 2025 · 10.1016/j.ultrasmedbio.2025.07.009
Abstract
Objective Transcranial ultrasound stimulation (TUS) is an emerging noninvasive brain-stimulation tool that is used to modulate neural circuits in humans. We investigated the effects of the application of very low-intensity TUS to the primary motor cortex on corticospinal excitability and motor performance in healthy individuals. Methods This crossover, randomized, single-blind study included 24 healthy volunteers. In Experiment 1, participants underwent three interventional conditions designed to evaluate the effects of different TUS intensities (16.0 mW/cm², 8.0 mW/cm², and sham) on corticospinal excitability, which was assessed by measuring the motor-evoked potential (MEP) amplitudes elicited by transcranial magnetic stimulation (TMS). In Experiments 2 and 3, participants underwent two interventional conditions to assess the effects of very low-intensity TUS (16.0 mW/cm² and sham) on spinal excitability (Experiment 2) and motor performance (Experiment 3). Spinal excitability was evaluated by measuring the F/M wave amplitude ratios and F-wave persistence using electrical stimulation of the ulnar nerve whereas motor performance was evaluated by asking the participants to complete a simple reaction-time (RT) task to measure RTs. Results MEP amplitudes significantly decreased immediately after 16.0 mW/cm² TUS, and 15 min after both 16.0 and 8.0 mW/cm² TUS. F/M wave amplitude ratios and F-wave persistence showed no significant changes. RTs significantly increased during both 16.0 mW/cm² and sham TUS, although no significant differences were found between the conditions. Conclusions Very low-intensity TUS decreased corticospinal excitability without altering spinal excitability or motor performance in healthy individuals.
Abstract via europepmc.
Exposures
Exposure 1: Unfocused 30 kHz continuous TUS over right M1
Target: primary motor cortex — “right M1”
Device: other named manufacturer · World Brain · Ultra-ma ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 30 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | 100 | ✓✓✓⚑ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | ⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 0.00318, 0.00635swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.00318, 0.00635swept | ✓✓✓ |
Continuous, unfocused sonication at 30 kHz: 300 ms sonications every 3 s (inter-stimulation interval) for a total of 20 min, at two intensities (16.0 and 8.0 mW/cm2 free-field Isp) plus sham.
Flags from extraction
exposures[0].free_field.isppa_w_cm2— Paper reports spatial peak intensity 'Isp' of 16.0 and 8.0 mW/cm2 (free-field), not Isppa by name; recorded in the Isppa field and converted to W/cm2. For continuous wave Isppa and Ispta coincide, but Ispta is left not_reported because the paper states this only for the simulated 8.0 mW/cm2 case.exposures[0].in_situ.isppa_w_cm2— k-Wave simulated at M1: Isppa 6.35 and 3.18 mW/cm2 (paper also gives simulated Isp 12.97 and 6.49 mW/cm2). The paper itself notes Isppa is lower than Isp, which is unusual for continuous wave.exposures[0].timing.waveform— Continuous, unfocused sonication of 300 ms repeated every 3 s for 20 min; recorded as continuous with the 300 ms burst as the sonication duration.exposures[0].timing.duty_cycle_pct— DC 100% stated in the same sentence as the 30 kHz and 300 ms parameters.auditory_control— Sham played a masking sound through earphones; participants wore earphones during TUS too, but whether the masking sound was also played during active TUS is not stated.exposures[0].device.family— Ultra-ma by World Brain (Tokyo); not a listed manufacturer so other_manufacturer.