Safety and efficacy of low intensity transcranial ultrasound stimulation for depression: A single-blind randomized controlled clinical study
Xin Cai, Wei Sun, Xiaodan Zheng, Ningding Ding, Mingshan Luo, Yiting Tu, De Meng, Yang Liu, Shuangfei Ding, Bo Yuan, Xiaojing Long
Journal of Affective Disorders 2026, 394, 120666 · 10.1016/j.jad.2025.120666
Abstract
Aims This study aimed to confirm the safety and effectiveness of transcranial ultrasound stimulation (TUS) in treating depression by targeting a subregion of the left dorsolateral prefrontal cortex (dlPFC). Methods A single-blind, randomized, sham-controlled clinical study was conducted involving 24 patients with depression in the TUS group and 12 in the sham group. Participants underwent psychiatric assessments and functional MRI scans. We employed an MR-compatible transducer, integrating dual navigation through optical guidance and MR acoustic radiation force imaging, to accurately target Brodmann area 46 (BA46) of the left dlPFC. The treatment group received active TUS, while the sham group received identical treatment without energy output, followed by actual TUS treatment. Results Following treatment, the TUS group exhibited significant improvements in depression and anxiety scores, as well as sleep quality, with benefits lasting up to four weeks. The sham group showed minor improvements after sham stimulation, but these became significant after subsequent real TUS treatment. Functional connectivity analysis revealed changes in the TUS group, particularly in connectivity with regions implicated in emotion processing, including the subgenual anterior cingulate cortex, ventral posterior cingulate cortex, and precuneus, all of which correlated with symptom improvements. Adverse effects of TUS were minimal and well-tolerated. Conclusion This study underscores the potential of low-intensity TUS as a safe and effective treatment for depression, with the capacity to modulate neural activity in targeted brain areas. Future research should emphasize optimizing TUS parameters and exploring its effects on other brain regions linked to depression.
Abstract via europepmc.
Exposures
Exposure 1: TUS to left dlPFC subregion BA46
Target: dorsolateral prefrontal cortex — “Brodmann area 46 (BA46) of the left dlPFC”
Device: other named manufacturer · GreenValley BrainTech (Shenzhen) Co. Ltd. · GVBT-1-H001 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 20pulse duration × PRF gives 20% | ✓✓✓ |
| Sonication duration (s) | 0.1 | ✓✓✓ |
| Free-field pressure (kPa) | 730 | ✓?⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 16.87 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.169 | ✓✓✓ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 410 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
The transducer was driven by an electronic control system to produce pulses with an operating frequency of 500 kHz, a pulse duration of 200us, a pulse repetition interval of 1 ms, and a pulse train duration of 100 ms. Each pulse train was delivered every 2 s for 20 min. Participants underwent 10 visits over a 12-day period, during which they received either active TUS or sham stimulation in the Brodmann area 46 (BA46) of the left dlPFC.
Flags from extraction
n_subjects— Paper never states a combined total of subjects exposed to real ultrasound (TUS group 24 + sham group 12 who crossed over to real TUS); group sizes listed instead.exposures[0].free_field.pressure_kpa— Paper gives 1.45 MPa peak-to-peak in one sentence and 0.73 MPa 'free-field peak negative pressure' in another for what appears to be the same measurement; the peak-negative value (0.73 MPa / 730 kPa) explicitly labelled 'free-field' was used here.auditory_control— Paper describes only a general procedural effort ('technically modifying the transducer assembly to standardize vibroacoustic characteristics') that does not match a specific auditory-control category; coded as other.exposures[0].device.family— GreenValley BrainTech is not one of the named manufacturers in the vocabulary; coded as commercial_other.