Aaron Loh, Grace Attalla, Ghazaleh Darmani, Can Sarica, Alexandre Boutet, Jurgen Germann, Gavin Elias, Steven Su, Houyou Fan, Sarah A. Iskin, Julianna Pijar, Jason Yuen, George M. Ibrahim, Mojgan Hodaie, Suneil K. Kalia, Robert Chen, Andrés Sebastian Castillo Lozano
BACKGROUND: Transcranial ultrasound stimulation (TUS) enables non-invasive neuromodulation of cortical and subcortical brain regions. Technological advances have facilitated rapid expansion of the field in recent years. However, the overall scope, methodological trends, and reporting practices of human TUS research remain unclear. OBJECTIVE: To characterize the global landscape of registered clinical trials using TUS for neuromodulation, including their design features, indications, targets, device platforms, and dissemination. METHODS: A systematic search of major international registries (ClinicalTrials.gov, WHO ICTRP, EUCTR, ChiCTR, CRiS, ANZCTR, JPRN, ISRCTN, and CTRI) was performed through September 2025. Interventional studies using low-intensity ultrasound for brain neuromodulation were included. Data were extracted on indication, target, device, design, enrollment, sponsorship, and publication linkage. RESULTS: A total of 177 unique clinical trials were identified. Registrations have increased sharply over time, with 27 trials registered between 2014 and 2019, and 150 trials registered in the last 5 years. The United States (52%) and China (18%) lead activity. Psychiatric disorders were the most common indication (32%), followed by healthy volunteer studies (16%), pain (11%), cognitive (11%), and movement disorder (9%) studies. Among trials specifying a target, over half (51%) targeted subcortical regions. A considerable proportion of studies were randomized, multi-arm, and double-blinded (40%). Device information was reported in 32% of trials, identifying 11 distinct commercial and prototype systems. Of completed trials, 37% were linked to a peer-reviewed publication. CONCLUSIONS: TUS clinical research is expanding rapidly but remains heterogeneous in design, targets, and device reporting. Enhanced transparency in trial registration and parameter documentation will facilitate the development of stronger study designs and encourage the field to direct its efforts toward understudied areas.