Mechanisms of Low-intensity Focused Ultrasound Targeting Striatal Circuits Underlying Auditory Hallucinations in Schizophrenia
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Caudate-superior temporal cortical (STC) connectivity
Study Overview
Brief 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.
Detailed 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 a promising therapeutic target. The current study builds on these findings by evaluating whether non-invasive neuromodulation of the caudate can normalize striatal-temporal network function and improve hallucination symptoms.
Study Objective:
This first-in-human, early Phase 1 investigator-initiated clinical trial will evaluate the safety, feasibility, tolerability, target engagement, and preliminary mechanistic effects of repeated-session low-intensity focused ultrasound (LIFU) targeting the caudate, a key striatal region implicated in auditory hallucinations in schizophrenia. The study will determine whether individualized LIFU can safely modulate deep corticostriatal circuits and reduce hallucination-related functional connectivity abnormalities while improving psychotic hallucination symptoms.
Study Design:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 64 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18-64 years of age, inclusive of all gender identities
- •Current DSM-5 diagnosis of schizophrenia
- •Persistent clinically-significant auditory hallucinations
- •No contraindications for MRI, confirmed via standard safety screening procedures
- •No neurological disorder
- •Clinically stable (outpatient past 12 weeks; same dose medications in 4 weeks)
- •Females will be tested for pregnancy and pregnant women will be excluded.
Exclusion Criteria
- •Clinically significant neurological disorder or MRI incompatibility
Arms & Interventions
Sham Sonication
Sham Unfocused Sonication
Intervention: LIFU (Device)
Active LIFU
Active LIFU targeting teh caudate
Intervention: LIFU (Device)
Outcomes
Primary Outcomes
Caudate-superior temporal cortical (STC) connectivity
Time Frame: Baseline and Post-Treatment ( Day 5)
We will compare functional connectivity using Fisher r-to-z values from the CONN toolbox between the caudate and STC after LIFU compared to baseline and the sham unfocused sonication condition
Auditory Hallucinations
Time Frame: Baseline and Post-Treatment (Weekly follow-up for 8 weeks)
We will compare hallucinations after LIFU to caudate with baseline and the sham unfocused sonication condition using the Visual Analog Scale (VAS) and Auditory Vocal Hallucination Rating Scales (AVHRS).
Secondary Outcomes
- Clinical Positive and Negative Symptoms(Baseline and Post-Treatment (Weekly follow-up for 8 weeks))