Audio Visual HallucinationsNCT03504579
Rt-fMRI Neurofeedback and AH in Schizophrenia
A study testing rt-fMRI neurofeedback in people with Audio Visual Hallucinations and Neurofeedback, run by Harvard Medical School (HMS and HSDM) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Audio Visual Hallucinations, Neurofeedback, Schizophrenia
- What is being tested?
- rt-fMRI neurofeedback
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2018to 30 Jun 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- a diagnosis of schizophrenia or schizoaffective disorder based on SCID interview (DSM-5) and
- the presence of auditory hallucinations (PANSS, item 3, score ≥4) with frequency of AH being at least once daily;
- age between 18-55 years;
- estimated IQ of above 80 as measured by WASI;
- English as the primary language;
- right-handed as determined by the Edinburgh Handedness Inventory (scoring + 60; Oldfield, 1971);
- an ability and desire to participate in the testing program as explained by an experimenter and confirmed with a written consent form.
Who cannot join
- history of ECT for the last 5 years;
- history of neurological illness or a traumatic head injury, defined as loss of consciousness for more than 5 minutes and/or structural sequelae following head trauma;
- history of severe or moderate alcohol (AUD) or substance use disorder (SUD) in the past five years, or mild AUD or SUD within the last year, according to DSM-5;
- the use, in the preceding year of steroids or barbiturates, which can affect cognitive function;
- hearing, vision or upper body impairment
- alcohol use in the last 24 hours;
Trial locations and contacts
1 site in 1 country.
United States1 site
Veterans Administration Health Care System
Brockton, Massachusetts, 02301
About this study
Official title: Real-time fMRI Feedback as a Tool to Mitigate Auditory Hallucinations in Schizophrenia
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.
Read the detailed description
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.
- Being tested
- rt-fMRI neurofeedback
- Keywords
- rt-fMRI, MRI, schizophrenia, auditory hallucinations, neurofeedback
- Medical subject headings
- Schizophrenia, Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rt-fMRI neurofeedbackOther
use of real time fMRI neurofeedback to achieve targeted brain changes
| Study group | Role | What they receive |
|---|---|---|
| rt-fMRI neurofeedback aimed at STG | Experimental | One session of rt-fMRI neurofeedback from the patient's STG. Receives: Other: rt-fMRI neurofeedback |
| sham rt-fMRI | Sham comparator | One session of rt-fMRI neurofeedback from the patient's motor cortex. Receives: Other: rt-fMRI neurofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
rt-fMRI neurofeedback from STG
changes in BOLD activation in STG
Measured: 1-2 weeks, post rt-fMRI session
Secondary outcomes (1)
rt-fMRI neurofeedback from mPFC
changes in BOLD activation in mPFC
Measured: 1-2 weeks, post rt-fMRI session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2018
- Study start1 Mar 2018
- Primary completion30 Mar 2022
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Audio Visual HallucinationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In the R61 phase of the study,changes in a target brain region(s) will be demonstrated after the rt-fMRI based neurofeedback session.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harvard Medical School (HMS and HSDM)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Margaret Niznikiewicz, Harvard Medical School (HMS and HSDM)
- Investigators
- margaret niznikiewicz, ph.d, Principal investigator, VA Boston Healthcare Systemsusan whitfield-Gabrieli, Ph.D., Principal investigator, Massachusetts Institute of Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03504579
- Sponsor's protocol ID
- 7304878-01
- Status last verified
- Nov 2022
- First submitted
- 29 Mar 2018
- Last updated
- 29 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40236821Morfini 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.
PubMed 38968807
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-time fMRI Feedback as a Tool to Mitigate Auditory Hallucinations in Schizophrenia
- ClinicalTrials.gov ID
- NCT03504579
- Acronym / sponsor ID
- 7304878-01
- Keywords
- rt-fMRI, MRI, schizophrenia, auditory hallucinations, neurofeedback
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Harvard Medical School (HMS and HSDM)University, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 30 Mar 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 20 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- In the R61 phase of the study,changes in a target brain region(s) will be demonstrated after the rt-fMRI based neurofeedback session.
| Arm | Type | Receives |
|---|---|---|
| rt-fMRI neurofeedback aimed at STG | Experimental | Other: rt-fMRI neurofeedbackOne session of rt-fMRI neurofeedback from the patient's STG. |
| sham rt-fMRI | Sham comparator | Other: rt-fMRI neurofeedbackOne session of rt-fMRI neurofeedback from the patient's motor cortex. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- a diagnosis of schizophrenia or schizoaffective disorder based on SCID interview (DSM-5) and
- the presence of auditory hallucinations (PANSS, item 3, score ≥4) with frequency of AH being at least once daily;
- age between 18-55 years;
- estimated IQ of above 80 as measured by WASI;
- English as the primary language;
Key exclusion criteria (6 listed)
- history of ECT for the last 5 years;
- history of neurological illness or a traumatic head injury, defined as loss of consciousness for more than 5 minutes and/or structural sequelae following head trauma;
- history of severe or moderate alcohol (AUD) or substance use disorder (SUD) in the past five years, or mild AUD or SUD within the last year, according to DSM-5;
- the use, in the preceding year of steroids or barbiturates, which can affect cognitive function;
- hearing, vision or upper body impairment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rt-fMRI neurofeedbackuse of real time fMRI neurofeedback to achieve targeted brain changes | Other | rt-fMRI neurofeedback aimed at STG, sham rt-fMRI |
Primary outcome
rt-fMRI neurofeedback from STG
Time frame: 1-2 weeks, post rt-fMRI session
changes in BOLD activation in STG
1 secondary outcome
rt-fMRI neurofeedback from mPFC
Time frame: 1-2 weeks, post rt-fMRI session
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Derived from this study: PubMed 40236821Zhang 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.
- Derived from this study: PubMed 38968807Morfini 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
margaret niznikiewicz, ph.d principal investigator
VA Boston Healthcare System
susan whitfield-Gabrieli, Ph.D. principal investigator
Massachusetts Institute of Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rt-fMRI neurofeedback in people with Audio Visual Hallucinations and Neurofeedback, run by Harvard Medical School (HMS and HSDM) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rt-fMRI neurofeedback from STG (time frame: 1-2 weeks, post rt-fMRI session). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03504579, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2022.