For one participant in a San Francisco study, the voices that had filled the day grew softer after focused ultrasound: “I feel it’s very peaceful.” The change is an early observation, not proof of a treatment, but it points to a new way researchers hope to help people whose hallucinations persist despite medication.
Auditory hallucinations—hearing voices other people do not hear—affect more than 70% of people with schizophrenia. About 40% continue to experience them even while taking antipsychotic medicines. At the University of California, San Francisco (UCSF), a research team is testing whether low-intensity focused ultrasound can safely reach a deep brain area linked to these experiences.
The first-in-human Phase I trial is led by Karuna Subramaniam, a professor of psychiatry. It uses a noninvasive wearable device made by Attune Neurosciences to direct ultrasound toward the caudate, a region within a larger brain structure called the striatum. Researchers are enrolling up to 12 participants to study safety and feasibility, as well as whether repeated sessions can reduce hallucinations for longer.
Each participant is scheduled to receive five daily sessions of active ultrasound and five sessions of a sham treatment, with a break between the two sets. The sham uses the same amount of ultrasound energy and is intended to feel like treatment, but does not focus the energy on a specific brain target. Comparing the conditions can help the team tell whether any change comes from targeting the caudate rather than from expectations or other general effects of taking part.
Researchers will also use resting-state functional MRI scans before and after treatment. These scans show how activity in different brain areas is connected while a person is at rest. The team will track the severity of voices, other psychiatric symptoms and mood, along with safety, comfort and possible side effects.
The trial follows preliminary findings published in the journal Brain Stimulation. In that earlier work, one session of focused ultrasound led to significant reductions in hallucinations, but the effects were temporary. Now the UCSF team is asking whether repeated sessions can make any relief last longer.
Some participants in the ongoing study have already reported that the voices eased after repeated treatment. One person, who had described voices as constant and disruptive, later said they were softer and seemed to be moving into the background. Such accounts are encouraging, but the study is small and still underway; they cannot yet show how often the treatment works or how long any benefit lasts.
Focused ultrasound is also being studied in a separate trial at NYU Langone Health. That team used a different device to target another brain region, the globus pallidus, and reported a modest but clear reduction in delusions among people with schizophrenia or schizoaffective disorder. The UCSF trial will add evidence about a different target and symptom. As enrollment continues, its results should help researchers judge whether this approach is safe and whether a larger study is warranted.