Summary:
A pilot clinical trial led by NYU Langone Health psychiatrists and biomedical engineers reveals that non-invasive transcranial ultrasound stimulation directed at the globus pallidus interna safely reduces delusions in individuals with schizophrenia and schizoaffective disorder. A single 10-minute session produced a clear, statistically meaningful decrease in delusion severity that persisted for up to one week compared to sham treatment, without significant adverse effects.
Key Facts:
- Non-Invasive Deep Circuit Modulation: Using MRI-guided transcranial ultrasound stimulation, researchers delivered focused acoustic energy to the globus pallidus interna, a deep basal ganglia hub linked to psychosis, without surgical incisions or implanted electrodes.
- Sustained Delusion Reduction: A single 10-minute ultrasound protocol lowered delusion severity by an average of 1.2 points on standardized clinical psychiatric scales, whereas scores rose by 0.4 points following sham exposure; therapeutic benefits lasted through the seven-day follow-up window.
- Favorable Safety Profile: Side effects were mild, transient, and equivalent between active and sham interventions (primarily mild fatigue and headache), demonstrating the feasibility of focused acoustic neuromodulation for treatment-resistant psychotic disorders.
Source: NYU Langone Health
Schizophrenia and schizoaffective disorder are chronic, complex neuropsychiatric conditions that severely impact daily functioning, often causing auditory and visual hallucinations alongside fixed, false beliefs known as delusions. While antipsychotic medications serve as the standard frontline treatment, an estimated 30% of patients experience persistent, treatment-resistant symptoms, and existing pharmacological options frequently carry heavy metabolic and neurological burdens.
Now, a pioneering cross-disciplinary study by psychiatrists and engineers at NYU Langone Health shows that acoustic waves can safely reach deep into the brain to alleviate these symptoms non-invasively.
Publishing October 20 in the journal npj Acoustics, the research team evaluated transcranial ultrasound stimulation (TUS) in 10 patients with chronic schizophrenia or schizoaffective disorder who experienced persistent psychotic symptoms despite ongoing drug therapy. The trial provides the first clinical evidence that focused acoustic neuromodulation can quiet psychotic delusions by precisely “tuning” subcortical circuits.
Accessing Deep Brain Hubs Without Surgery
Transcranial ultrasound stimulation uses gentle, low-intensity focused sound waves to excite or suppress neural firing in targeted subcortical structures. While transcranial magnetic stimulation (TMS) and direct current stimulation (tDCS) are established clinical tools, their electrical and magnetic fields disperse rapidly, making it difficult to modulate structures buried deep beneath the cerebral cortex without affecting overlying tissue.
“Unlike other emerging techniques that modulate brain circuits, transcranial ultrasound stimulation offers a unique opportunity to precisely target very small regions that affect thinking and behavior,” said co-senior author Shy Shoham, PhD, professor of neuroscience and ophthalmology at NYU Grossman School of Medicine and director of the Tech4Health Institute at NYU Langone.
The investigators targeted the globus pallidus interna (GPi), a key subcortical structure within the cortico-striato-thalamo-cortical loop that coordinates movement, cognition, and emotional processing. Prior work by lead author Wei Qi, MD, demonstrated that pathological hyperactivity and network dysregulation within this specific basal ganglia node are closely tied to delusion severity and medication non-responsiveness.
Double-Blind Trial Demonstrates Symptom Relief
In the double-blind, sham-controlled crossover trial, each participant received two experimental sessions spaced one week apart in randomized order: one active ultrasound treatment and one sham control. During the sham visit, the transducer device was positioned identically on the scalp and powered on, but acoustic transmission was physically blocked.
Guided by high-resolution structural MRI scans, the clinical team delivered ultrasound waves directly to the globus pallidus interna for 10 minutes using 30-second on/off pulsing cycles.
The results showed a clear divergent clinical response:
- Active Ultrasound: Patients experienced an average 1.2-point reduction in delusion severity on standardized clinical rating scales.
- Sham Control: When receiving the inert procedure, delusion scores worsened by an average of 0.4 points.
- Persistent Benefit: The therapeutic reduction in delusion severity was maintained across the entire seven-day post-treatment observation period.
Adverse events, including transient headaches, mild fatigue, and brief fluctuations in psychotic distress, were minor, self-limiting, and showed no significant difference between the active and sham conditions.
“Our results offer early evidence that a single session of transcranial ultrasound stimulation can safely ‘tune’ a brain circuit linked to psychosis and lead to a noticeable drop in delusions,” said lead author Wei Qi, MD, clinical assistant professor in the Department of Psychiatry at NYU Grossman School of Medicine.
The Future of Acoustic Neuromodulation in Psychiatry
The study opens new possibilities for treating psychiatric illnesses that have historically resisted therapeutic innovation.
“These promising early findings suggest that further work is needed to establish whether targeted ultrasound could one day supplement or even replace standard medicines for schizophrenia,” said senior author Donald C. Goff, MD, the Marvin Stern Professor of Psychiatry, vice chair of research in the Department of Psychiatry at NYU Grossman School of Medicine, and director of NYU Langone’s Schizophrenia Research Group. “This work also demonstrates that focused ultrasound can be used to examine brain circuits relevant to psychiatric illness.”
Building on these early results, the NYU Langone psychiatry and biomedical engineering teams are designing expanded clinical trials to assess whether multi-session ultrasound regimens produce deeper or more durable symptom remission. Future trials will also incorporate personalized acoustic modeling to calibrate sound-wave intensity to individual skull thickness and brain anatomy, optimizing target engagement in the deep brain.
Funding: Funding for the pilot study was provided by the Doris Duke Foundation Fund to Retain Clinical Scientists, the Brain & Behavior Research Foundation, and the Max G. Schlapp Mental Hygiene Fund.
Along with Drs. Qi, Goff, and Shoham, NYU Langone researchers involved in the study were Alon Gilad, ME; Michele Santacatterina, PhD; Spencer Brinker, PhD; Gillian Capichioni; and Fumika Ando.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurotech and schizophrenia Research:
- Media Contact: Shira Polan
- Source: NYU Langone Health
- Image Credit: Image credited to Neuroscience News
- Original Research is Open Access: npj Acoustics (Oct 1, 2026). “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
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 Ispta 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.
