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Auditory hallucinations in schizophrenia are one of the major symptoms of this disease and a major source of psychological discomfort. They are often difficult or impossible to treat with existing methods. This study will test the use of real-time fMRI neurofeedback to mitigate auditory verbal hallucinations in patients whose hallucinations are resistant to medication. Half of the patients will receive real time fMRI neurofeedback from a brain region involved in auditory hallucinations and half will receive it from motor cortex.
Auditory verbal hallucinations (AH) have long been a hallmark of schizophrenia (SZ) and are one of its major diagnostic features. They are difficult to manage with existing treatment options. Here, neurofeedback will be used to regulate the superior temporal gyrus (STG) activation which will not only lead to activation changes in the STG, but also to changes in the default mode network (DMN).
The investigators will study SZ patients with medication resistant AH in the rt-fMRI intervention arm and in the sham-rt-fMRI arm. In both arms, the task and the rt-fMRI session structure will be identical. The SZ-intervention group will receive feedback from the STG while SZ-sham group will receive feedback from the motor cortex. In addition, 2 functional fMRI tasks will examine the effect of rt-fMRI neurofeedback and of sham-rt-fMRI on brain response.
The investigators will randomly assign 48 SZ patients to either SZ-intervention (n=24) or SZ-sham-rtfMRI (n=24). The STG targeted neurofeedback is predicted to bring changes in brain regions involved in AH (STG and DMN) in SZ-intervention group only. The R61 GO criterion will be BOLD signal reduction in the STG, and resting state connectivity reduction between MPFC-PCC, post rt-fMRI-feedback in SZ-intervention group.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rt-fMRI neurofeedback aimed at STG | Experimental | One session of rt-fMRI neurofeedback from the patient's STG. |
|
| sham rt-fMRI | Sham Comparator | One session of rt-fMRI neurofeedback from the patient's motor cortex. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rt-fMRI neurofeedback | Other | use of real time fMRI neurofeedback to achieve targeted brain changes |
|
| Measure | Description | Time Frame |
|---|---|---|
| rt-fMRI neurofeedback from STG | changes in BOLD activation in STG | 1-2 weeks, post rt-fMRI session |
| Measure | Description | Time Frame |
|---|---|---|
| rt-fMRI neurofeedback from mPFC | changes in BOLD activation in mPFC | 1-2 weeks, post rt-fMRI session |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| margaret niznikiewicz, ph.d | VA Boston Healthcare System | Principal Investigator |
| susan whitfield-Gabrieli, Ph.D. | Massachusetts Institute of Technology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Veterans Administration Health Care System | Brockton | Massachusetts | 02301 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40236821 | Derived | Zhang J, Tusuzian E, Morfini F, Bauer CCC, Stone L, Awad A, Shinn AK, Niznikiewicz MA, Whitfield-Gabrieli S. Brain Structural and Functional Neuroimaging Features are Associated With Improved Auditory Hallucinations in Patients With Schizophrenia After Real-Time fMRI Neurofeedback. Depress Anxiety. 2025 Apr 8;2025:2848929. doi: 10.1155/da/2848929. eCollection 2025. | |
| 38968807 |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jun 2, 2023 | |
| Reset | Feb 1, 2024 | |
| Release | May 17, 2024 | |
| Reset | Jun 12, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jun 2, 2023 | Feb 1, 2024 | |||
| May 17, 2024 |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D006212 | Hallucinations |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
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In the R61 phase of the study,changes in a target brain region(s) will be demonstrated after the rt-fMRI based neurofeedback session.
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| Morfini F, Bauer CCC, Zhang J, Whitfield-Gabrieli S, Shinn AK, Niznikiewicz MA. Targeting the superior temporal gyrus with real-time fMRI neurofeedback: A pilot study of the indirect effects on self-referential processes in schizophrenia. Schizophr Res. 2024 Aug;270:358-365. doi: 10.1016/j.schres.2024.06.036. Epub 2024 Jul 4. |
| Jun 12, 2024 |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |