Mechanisms of Low-intensity Focused Ultrasound Targeting Striatal Circuits Underlying Auditory Hallucinations in Schizophrenia
University of California, San Francisco
Summary
Individuals with schizophrenia often experience persistent auditory hallucinations despite treatment with antipsychotic medications. Research suggests that abnormal communication between the striatum and the auditory cortex contributes to hallucinations. This first-in-human, proof-of-concept Phase 1 study will evaluate the safety, feasibility, and preliminary effects of repeated-session low-intensity focused ultrasound (LIFU), a non-invasive neuromodulation technique targeting the striatum. The study will examine whether LIFU can safely modulate brain circuits involved in hallucinations, reduce abnormal communication between the striatum and auditory cortex, and improve auditory hallucination symptoms.
Description
Background: Auditory hallucinations affect approximately 70% of individuals with schizophrenia and often persist despite antipsychotic treatment, contributing substantially to disability and reduced quality of life. Neuroimaging studies have consistently demonstrated abnormal functional connectivity between the striatum and superior temporal cortex, implicating corticostriatal circuitry in the generation and maintenance of hallucinations. Among striatal regions, the caudate has been associated with aberrant self-monitoring, abnormal predictive processing, and hallucination severity, making it…
Eligibility
- Age range
- 18–64 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. 18-64 years of age, inclusive of all gender identities 2. Current DSM-5 diagnosis of schizophrenia 3. Persistent clinically-significant auditory hallucinations 4. No contraindications for MRI, confirmed via standard safety screening procedures 5. No neurological disorder 6. Clinically stable (outpatient past 12 weeks; same dose medications in 4 weeks) 7. Females will be tested for pregnancy and pregnant women will be excluded. Exclusion Criteria: Clinically significant neurological disorder or MRI incompatibility
Interventions
- DeviceLIFU
MRI-guided, neuronavigated low-intensity focused ultrasound (LIFU) delivered to the caudate target will be compared to sham unfocused sonication delivered using the same device and procedures as the active intervention but without focal ultrasound energy to the target.
Location
- University of California, San FranciscoSan Francisco, California