Transcranial ultrasound stimulation of the right globus pallidus interna in schizophrenia: A randomized, sham-controlled pilot study
Wei Qi, Alon Gilad, Michele Santacatterina, Spencer Brinker, Gillian Capichioni, Fumika Ando, Shy Shoham, Donald C. Goff
npj Acoustics 2026 · 10.1038/s44384-026-00076-3
Abstract
Functional abnormalities of the globus pallidus interna (GPi) are linked to psychosis severity and treatment response in schizophrenia. Transcranial ultrasound stimulation (TUS) is a noninvasive method for precisely targeting deep brain structures. The effects of GPi-targeted TUS on psychosis had not been examined. We conducted a random-order, sham-controlled, crossover pilot study assessing safety, tolerability, and preliminary efficacy of right GPi TUS for psychotic symptoms. Ten outpatients (mean age 37.5; 50% female) with schizophrenia or schizoaffective disorder and persistent psychosis received one TUS and one sham session, one week apart. TUS was MRI-guided, targeting right GPi with a 350 kHz transducer (100 Hz pulse repetition frequency, 5% duty cycle, in situ I spta 400 mW/cm²). Outcomes-delusion experience sampling assessment (DESA) and auditory hallucinations rating scale (AHRS)-were measured before, during, and immediately, 1 h, 1, and 7 days after stimulation. DESA scores decreased significantly more after TUS than sham ( p = 0.002, Cohen's d = 0.68); AHRS and cognition changes were not significant. Mild transient adverse effects occurred in both conditions; none were serious. GPi-targeted TUS was safe, well-tolerated, and associated with a preliminary reduction in delusional severity, warranting further study in larger, randomized trials. ClinicalTrials.gov: NCT05643196, registered 21 November 2022.
Abstract via europepmc.
Exposures
Exposure 1: Right GPi TUS (350 kHz)
Target: globus pallidus internus — “right globus pallidus interna (GPi)”
Device: custom-built · custom-made single-element fixed-depth 350 kHz transducer with plano-concave Delrin lens (STEMiNC SMD85T6R111 element) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓⚑ |
| Free-field pressure (kPa) | 1,340 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 60.1 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 3 | ✓✓✓⚑ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 500 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 7.9 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.4 | ✓✓✓ |
0.5 ms rectangular pulses at a 100 Hz PRF (10 ms pulse repetition interval, 5% duty cycle); the 10-min protocol consisted of ten cycles of 30 s on and 30 s off. One TUS and one sham session one week apart.
Flags from extraction
blinding— Participants and all team members except the bioengineer were blinded, but the authors state the study should not be considered fully double-blinded and 6 of 10 guessed the condition correctly.exposures[0].in_situ.pressure_kpa— In situ values are derived by derating free-water output with a maximum skull transmission coefficient (upper bound) and a brain attenuation of 0.5 dB/cm/MHz over 6 cm; the abstract and results also give an estimated through-skull Ispta range of 0.29-0.4 W/cm2.exposures[0].timing.sonication_duration_s— Ten cycles of 30 s on and 30 s off over 10 min; 30 s is the length of each uninterrupted train.exposures[0].free_field.ispta_w_cm2— Free-water Ispta (3 W/cm2) is read from LaTeX-garbled text.n_sessions_per_subject— One active and one sham session, one week apart; 2 total sessions.exposures[0].device.family— Custom single-element transducer fabricated by the authors around a STEMiNC piezo element; no commercial transducer maker named.