Transcranial ultrasound stimulation of the right globus pallidus interna in schizophrenia: A randomized, sham-controlled pilot study

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.