Immediate excitatory effect of transcranial ultrasound intensity on the human primary motor cortex: a double-blind, sham-controlled and crossover study
Shu Cheng, Moxian Chen, Shan Liang, Yanpin Zhao, Xiaojing Long, De Meng, Feifei Zhu, Jing Zhang, Zhongfei Bai, Lijuan Ao
Frontiers in Human Neuroscience 2026, 20 · 10.3389/fnhum.2026.1884060
Abstract
Objective To systematically characterize the intensity-dependent effects of low-intensity transcranial ultrasound stimulation (TUS) on excitability in the human primary motor cortex (M1) and to identify an effective intensity threshold for inducing immediate excitatory changes. Methods In a randomized, double-blind, sham-controlled crossover design, twenty-five healthy right-handed adults (mean age, 24.0 ± 3.3 years) received 20 min of 500 kHz TUS to their M1 hotspot. Five sessions were conducted, each employing a different spatial peak pulse average intensity (ISPPA: 3, 6, 9, or 12 W/cm 2 or sham stimulation in the free-field). Corticospinal and intracortical excitability were assessed immediately before and after sonication using single and paired-pulse transcranial magnetic stimulation (TMS) protocols to measure motor-evoked potential (MEP) amplitudes, short and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and cortical silent period (cSP). Results A clear intensity-dependent effect was observed. Only sonication at 12 W/cm 2 significantly increased MEP amplitudes ( p = 0.036), indicating enhanced corticospinal excitability. TUS also significantly shortened the cSP duration at intensities of 6 ( p = 0.039), 9 ( p = 0.036), and 12 ( p = 0.003) W/cm 2 compared with pre-TUS. Notably, these changes occurred without any significant modulation of intracortical measures (SICI, LICI, and ICF) across all conditions. The observed excitatory effect was not correlated with baseline MEP amplitude or gender. Conclusion Our findings demonstrate that TUS modulates human M1 excitability in a selective and intensity-dependent manner, identifying an ISPPA of 12 W/cm 2 as a critical threshold for driving corticospinal potentiation. This provides a rational basis for parameter selection in future TUS protocols and advances its development as a precision tool for therapeutic applications in neurological disorders. Clinical trial registration Identifier, ChiCTR2600125507.
Abstract via europepmc.
Exposures
Exposure 1: Active TUS to M1 hotspot (ISPPA 3, 6, 9, 12 W/cm2)
Target: primary motor cortex — “M1 hotspot”
Device: other named manufacturer · GreenValley BrainTech Medical Technology Co. Ltd. ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.3 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 200 | ✓✓✓ |
| Duty cycle (%) | 6pulse duration × PRF gives 6% | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 3, 6, 9, 12swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.18, 0.36, 0.54, 0.72swept | ✓✓✓ |
| 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 |
Pulse Duration (PD) = 0.3 ms, Pulse Repetition Interval (PRI) = 5 ms, Pulse Train Duration (PTD) = 1 s, Inter-Stimulus Interval (ISI) = 5 s, Sonication Period (SP) = 6 s, PRF = 200 Hz, DC = 6%. Each 1-s pulse train was delivered every 6 s, with total sonication delivered for 20 minutes per session.
Flags from extraction
sham_type— Sham delivered minimum-dosage acoustic energy (ISPPA = 0.08 W/cm2 in free field) rather than a fully inactive transducer, blocked output, or sound-only condition; classified as 'other'.exposures[0].in_situ— Paper states intensities were quantified only in free water and explicitly notes they do not account for skull attenuation/phase aberration; no in-situ estimate was given.exposures[0].device.model— Manufacturer given (GreenValley BrainTech Medical Technology Co. Ltd.) but no specific model name/number stated.