First-in-Human Trial Deploys Focused Ultrasound to Disrupt Auditory Hallucinations in Schizophrenia

Researchers at the University of California San Francisco have launched a pioneering clinical trial to treat auditory hallucinations in schizophrenia using targeted sound waves. The first-in-human Phase 1 study deploys low-intensity focused ultrasound to safely modulate deep brain circuits without requiring invasive surgery.[1][4]

The trial targets a persistent and devastating challenge in modern psychiatric care, as auditory hallucinations affect more than 70 percent of individuals diagnosed with schizophrenia. For many patients, these distressing symptoms remain entirely unresponsive to standard pharmacological interventions.[1][4]

Despite strict adherence to antipsychotic medications, approximately 40 percent of patients continue to experience persistent voices. This treatment-resistant population has long lacked viable medical alternatives, leaving a critical gap in mental health care that researchers are now attempting to close.[1]

"For many people with schizophrenia, hearing voices remains a persistent and distressing problem despite medication," said Dr. Karuna Subramaniam, a professor of psychiatry at UCSF and the lead investigator of the new trial. "Our goal is to determine whether LIFU can safely and noninvasively target the caudate."[1]

Targeting Deep Brain Circuits

The UCSF study, registered as NCT07710989, utilizes a non-invasive wearable device developed by Attune Neurosciences. The technology delivers low-intensity focused ultrasound, or LIFU, directly through the skull to reach specific subcortical structures with millimeter precision.[1][4]

Unlike traditional non-invasive brain stimulation methods such as transcranial magnetic stimulation, which primarily affect the brain's surface, LIFU can safely penetrate deeper regions. This unique capability allows researchers to directly target the caudate, a key region within the striatum heavily implicated in hallucination generation.[4][6]

Neuroimaging studies have consistently demonstrated abnormal functional connectivity between the striatum and the superior temporal cortex in patients who hear voices. This aberrant signaling creates a continuous loop of abnormal predictive processing that current neurotransmitter-based medications often fail to disrupt.[4][6]

The Phase 1 trial aims to enroll up to 12 participants who have experienced continuous mild or greater hallucinations for at least four weeks. Each patient will undergo a rigorous crossover design to evaluate the experimental therapy's safety, tolerability, and preliminary efficacy.[1][4]

Participants will receive five daily sessions of active LIFU targeting the caudate, followed by a designated washout period, and then five sessions of a sham control. The unfocused control condition delivers the exact same amount of acoustic energy to preserve the sensory experience without targeting a specific brain region.[1][4]

Early Clinical Responses

Preliminary responses from the initial patients enrolled in the UCSF trial have been highly encouraging for the research team. Investigators report that participants are experiencing noticeable and significant reductions in hallucination severity following the repeated ultrasound sessions.[1]

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One early participant described a profound shift in their daily experience following the acoustic therapy, noting simply to researchers, "My mind is really quiet." These initial observations suggest that the neuromodulation is successfully disrupting the abnormal corticostriatal communication responsible for the voices.[1]

To objectively measure these neurological changes, the clinical team is utilizing resting-state functional MRI scans captured before and immediately after the sonication sessions. The advanced imaging aims to confirm whether the active LIFU effectively reduces the abnormal coupling between the striatum and the auditory cortex.[1][4]

The convergence of symptom improvement with measurable changes in deep brain connectivity provides vital mechanistic proof-of-concept evidence. It suggests that the striatal circuit is not just a passive biomarker for psychosis, but a highly viable therapeutic target for future interventions.[6]

Parallel Success in Delusion Treatment

The UCSF trial arrives alongside parallel breakthroughs in acoustic neuromodulation for other severe symptoms of schizophrenia. A recent pilot study led by NYU Langone Health demonstrated that a similar ultrasound technique can safely alleviate psychotic delusions in treatment-resistant patients.[1][5]

Published in the journal npj Acoustics on October 20, 2026, the NYU trial targeted a different deep brain structure known as the globus pallidus interna. The study enrolled 10 outpatients with chronic schizophrenia or schizoaffective disorder who experienced persistent psychotic symptoms despite ongoing drug therapy.[5]

Guided by high-resolution structural MRI scans, the clinical team delivered ultrasound waves directly to the target region for a single 10-minute session. The researchers utilized precise 30-second on-and-off pulsing cycles to safely excite or suppress neural firing within the subcortical hub.[5]

The results revealed a clear and divergent clinical response between the active and control groups. Patients receiving the active ultrasound experienced an average 1.2-point reduction in delusion severity on standardized clinical rating scales, marking a statistically meaningful improvement.[5]

By contrast, when the exact same patients received the sham version of the treatment, their delusion scores actually worsened by an average of 0.4 points. The therapeutic reduction in delusion severity was successfully maintained across the entire seven-day post-treatment observation period.[5]

A Favorable Safety Profile

Across both the UCSF and NYU clinical trials, the safety profile of low-intensity focused ultrasound has remained highly favorable. The non-invasive nature of the procedure entirely eliminates the severe risks of infection and surgical complications associated with deep brain stimulation implants.[1][5][6]

Adverse events reported during the trials have been minor, self-limiting, and statistically similar between the active and sham conditions. Participants have occasionally noted transient headaches, mild fatigue, and brief fluctuations in psychotic distress, none of which required medical intervention.[5][6]

"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 Dr. Wei Qi, the lead author of the NYU study.[5]

The Focused Ultrasound Foundation, which is actively funding the UCSF trial, views these parallel developments as a significant medical milestone. The foundation notes that the technology offers a fundamentally novel approach by using mechanical acoustic energy rather than systemic chemical intervention.[1]

The Path Forward

While the initial clinical data is highly promising, researchers caution that these remain early-stage feasibility studies with inherently small sample sizes. The long-term therapeutic relevance of targeting the caudate or globus pallidus requires confirmation in much larger, adequately powered clinical trials.[6]

Future studies will need to address specific methodological challenges, such as bone-conducted auditory confounds that can sometimes compromise patient blinding during ultrasound delivery. Advanced brain imaging will also be necessary to customize the ultrasound intensity and precise targeting for each individual's unique neuroanatomy.[6]

If these early successes can be replicated and sustained over longer periods, focused ultrasound could eventually supplement or even replace standard antipsychotic medications for some patients. For now, the ongoing trials represent a crucial first step toward silencing the persistent voices that have long evaded medical science.[1][6]