Summary:
A small, randomized pilot study led by psychiatrists and biomedical engineers at NYU Langone Health found that a single non-invasive session of MRI-guided transcranial ultrasound stimulation (TUS) targeting the globus pallidus interna (GPi) safely reduced delusional symptoms in people living with schizophrenia and schizoaffective disorder. Ten minutes of focused ultrasound produced a statistically significant decrease in delusion severity that persisted through a one-week follow-up, with no serious adverse events reported.
Key Facts:
- Non-invasive deep brain targeting: MRI guidance allowed clinicians to deliver concentrated acoustic energy to the GPi, a subcortical basal ganglia structure implicated in psychosis, without surgery or implanted electrodes.
- Symptom improvement after a single session: Participants showed an average 1.2-point reduction in delusion severity on standardized psychiatric measures after active ultrasound, while scores increased slightly after the sham procedure; effects were observed across the seven-day follow-up.
- Well tolerated: Reported side effects were mild and transient—mainly headache and fatigue—and occurred at similar rates in both the active and sham conditions, supporting the short-term safety and tolerability of focused acoustic neuromodulation in this population.
Source: NYU Langone Health
Schizophrenia and schizoaffective disorder are chronic neuropsychiatric conditions that can profoundly disrupt daily life. Alongside hallucinations, many affected individuals experience firmly held false beliefs, or delusions. Although antipsychotic medications are the mainstay of treatment, about 30% of patients have symptoms that remain resistant to standard therapies, and current drugs can produce significant metabolic and neurological side effects.
This interdisciplinary pilot study demonstrates that focused acoustic waves can non-invasively reach and modulate deep brain circuits associated with psychosis, offering a potential new approach for treatment-resistant symptoms.
Published October 20 in npj Acoustics, the trial enrolled 10 outpatients with chronic schizophrenia or schizoaffective disorder who continued to experience psychotic symptoms despite medication. The study delivers the first clinical evidence that precisely targeted transcranial ultrasound stimulation can reduce the intensity of delusions by modulating subcortical circuitry.
Accessing Deep Brain Hubs Without Surgery
Transcranial ultrasound stimulation uses low-intensity, focused sound waves to influence neural activity within specific subcortical regions. Unlike transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS), which disperse electrical or magnetic fields and have limited depth specificity, focused ultrasound can reach small deep structures while minimizing effects on overlying cortex.
The research team targeted the globus pallidus interna (GPi), a central node in the cortico‑striatothalamo‑cortical circuit involved in movement, cognition, and emotion. Prior investigations by the study group had linked abnormal GPi activity to greater delusion severity and to poor response to medication, making it a logical target for neuromodulation.
Double-Blind Trial Demonstrates Symptom Relief
This double-blind, sham-controlled crossover trial gave each participant two sessions one week apart in randomized order: one active TUS session and one sham session. The sham procedure mimicked the active setup with the device positioned and powered on, but acoustic transmission was blocked so no therapeutic sound waves reached the brain.
Using high-resolution structural MRI for navigation, clinicians applied ultrasound to the right GPi for 10 minutes in 30-second on/off pulse cycles. Delusions and auditory hallucinations were assessed before, during, immediately after, one hour after, and at one and seven days following stimulation.
- Active ultrasound: Average delusion severity decreased by 1.2 points on standardized scales after TUS.
- Sham control: During the sham session, delusion scores increased slightly by an average of 0.4 points.
- Durable short-term effect: The reduction in delusions persisted across the full seven-day observation period.
Other measured outcomes, including auditory hallucination ratings and cognitive testing, did not show statistically significant changes in this small sample. Mild, transient adverse events—such as brief headaches, mild fatigue, and short fluctuations in psychotic distress—occurred in both active and sham sessions without serious complications.
“These results provide initial clinical proof that a single session of transcranial ultrasound can safely modulate a deep brain circuit linked to psychosis and reduce delusional severity,” said lead author Wei Qi, MD, of NYU Grossman School of Medicine.
The Future of Acoustic Neuromodulation in Psychiatry
The study opens a path for further research into acoustic neuromodulation as a psychiatric treatment, particularly for conditions that have shown limited response to current therapies.
Senior author Donald C. Goff, MD, noted that these promising early findings justify expanded trials to test multi-session regimens and longer-term outcomes. Future studies will aim to personalize acoustic models to account for individual skull thickness and brain anatomy, improving precision and consistency of target engagement in deep structures like the GPi.
Funding: The pilot study was supported by the Doris Duke Foundation Fund to Retain Clinical Scientists, the Brain & Behavior Research Foundation, and the Max G. Schlapp Mental Hygiene Fund.
Key study contributors from NYU Langone included Wei Qi, MD; Alon Gilad, ME; Michele Santacatterina, PhD; Spencer Brinker, PhD; Gillian Capichioni; Fumika Ando; Shy Shoham, PhD; and Donald C. Goff, MD.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The full journal paper was reviewed in preparing this summary.
- Additional explanatory context was provided by editorial staff.
About this neurotech and schizophrenia Research:
- Media Contact: Shira Polan
- Source: NYU Langone Health
- Image Credit: Image credited to Neuroscience News
- Original Research (Open Access): npj Acoustics (Oct 1, 2026). Title: “Transcranial ultrasound stimulation of the right globus pallidus interna in schizophrenia: A randomized, sham-controlled pilot study.” Authors: Wei Qi, Alon Gilad, Michele Santacatterina, Spencer Brinker, Gillian Capichioni, Fumika Ando, Shy Shoham & Donald C. Goff.
- DOI: 10.1038/s44384-026-00076-3
Abstract
Transcranial ultrasound stimulation of the right globus pallidus interna in schizophrenia: A randomized, sham-controlled pilot study
Abnormal function of the globus pallidus interna (GPi) has been associated with the severity of psychotic symptoms and with treatment response in schizophrenia. Transcranial ultrasound stimulation (TUS) is a noninvasive technique capable of precisely targeting deep brain structures.
This pilot study tested the safety, tolerability, and preliminary efficacy of MRI-guided TUS directed at the right GPi in a randomized, sham-controlled, crossover design. Ten outpatients (mean age 37.5; 50% female) with schizophrenia or schizoaffective disorder and persistent psychosis received one active TUS session and one sham session one week apart. TUS parameters included a 350 kHz transducer with a 100 Hz pulse repetition frequency and a 5% duty cycle, delivered within established safety limits. Primary outcomes included a delusion experience sampling assessment (DESA) and an auditory hallucination rating scale (AHRS), measured at multiple time points up to seven days after stimulation.
DESA scores declined significantly more after active TUS than after sham (p = 0.002, Cohen’s d = 0.68). Changes in AHRS and cognitive measures were not statistically significant in this small sample. Mild, transient adverse effects were observed in both conditions; none were serious. The findings indicate that GPi-targeted TUS is safe and well tolerated and that it may produce a short-term reduction in delusional severity, supporting the need for larger randomized trials to confirm and extend these results.
ClinicalTrials.gov: NCT05643196, registered 21 November 2022.