fMRI Neurofeedback for Schizophrenia with Auditory Hallucinations

Overseen By Clemens Bauer, phd

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Harvard Medical School (HMS and HSDM)

Disqualifiers: Neurologic illness, Major head trauma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 sessions

104 Participants Needed

Trial Summary

What is the purpose of this trial?

Neurofeedback intervention aimed to regulate the superior temporal gyrus (STG) activation and default mode network (DMN) connectivity as well as to reduce the auditory hallucinations (AH) schizophrenia patients with medication resistant AH.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators.

What data supports the effectiveness of the treatment sham-rt-fMRI-Neurofeedback for schizophrenia with auditory hallucinations?

Research shows that real-time fMRI neurofeedback can help people with schizophrenia who experience auditory hallucinations by teaching them to control brain activity in specific areas, like the superior temporal gyrus. This approach has led to reduced hallucination symptoms in some patients, suggesting it could be a promising alternative for those who don't respond to traditional medications. ^{1 2 3 4 5}

Is fMRI neurofeedback safe for humans?

fMRI neurofeedback is generally considered safe for humans, as it is a non-invasive technique that has been used in various studies without significant safety concerns reported. However, individual experiences may vary, and more research is needed to fully understand its long-term safety. ^{1 2 4 5 6}

How is the treatment 'fMRI Neurofeedback for Schizophrenia with Auditory Hallucinations' different from other treatments?

This treatment is unique because it uses real-time fMRI neurofeedback to help patients with schizophrenia learn to control brain activity in specific areas associated with auditory hallucinations, offering a non-drug alternative for those who do not respond to traditional antipsychotic medications. ^{1 2 4 5 7}

Research Team

margaret niznikiewicz

Principal Investigator

Boston VA Research Institute, Inc.

Eligibility Criteria

This trial is for individuals with schizophrenia or schizoaffective disorder who experience auditory hallucinations that haven't improved with medication. They must be diagnosed using DSM-5 criteria and have a verbal IQ above 70. People cannot join if they've had major head trauma, neurological illness, electroconvulsive therapy, or substance abuse issues within the last five years.

Inclusion Criteria

My hearing voices are not getting better with medication.

I have been diagnosed with schizophrenia or schizoaffective disorder.

Exclusion Criteria

You have misused alcohol or drugs in the last five years.

Your ability to understand and use language is below a certain level.

You are dependent on alcohol or drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 sessions of real-time fMRI neurofeedback targeting the superior temporal gyrus (STG) or sham feedback from the motor cortex

5 sessions

Follow-up

Participants are monitored for changes in auditory hallucinations and brain connectivity post-intervention

0-4 weeks

Treatment Details

Interventions

• sham-rt-fMRI-Neurofeedback
• stg-rt-fMRI-Neurofeeback

Trial Overview The study tests neurofeedback interventions targeting the superior temporal gyrus (STG) to manage activation and connectivity in the brain's default mode network (DMN), aiming to reduce auditory hallucinations in participants resistant to standard treatments.

Participant Groups

Group I: stg-rt-fMRI Experimental Treatment 1 Intervention

will receive feedback from the STG

Group II: sham-rt-fMRI Placebo Group 1 Intervention

will receive feedback from the motor cortex

Who Is Running the Clinical Trial?

Harvard Medical School (HMS and HSDM)

Lead Sponsor

Trials

208

Recruited

1,421,000+

Boston VA Research Institute, Inc.

Lead Sponsor

Trials

24

Recruited

10,800+

Northeastern University

Collaborator

Trials

103

Recruited

72,600+

Mclean Hospital

Collaborator

Trials

221

Recruited

22,500+

Cambridge Health Alliance

Collaborator

Trials

65

Recruited

22,400+

Findings from Research

Auditory-verbal hallucinations (AVH) can cause significant distress in individuals with schizophrenia, and traditional antipsychotic medications often fail to help about 30% of these patients, highlighting the need for new treatment approaches.

Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) is being explored as a potential treatment for AVH, allowing individuals to gain voluntary control over their brain activity, which could lead to new therapeutic strategies for managing these distressing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances. Humpston, C., Garrison, J., Orlov, N., et al.[2021]

Auditory-verbal hallucinations (AVHs) affect over 25% of patients who do not respond to traditional treatments, highlighting the need for innovative therapies like fMRI-based neurofeedback (fMRI-NF) that allows patients to gain control over their brain activity.

The development of fMRI-NF protocols can be enhanced by targeting specific brain areas involved in AVHs, using both 'trait markers' for persistent vulnerabilities and 'state markers' for real-time activity during hallucinations, which could lead to effective new treatments for those with refractory symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating Neurocognitive Models of Auditory-Verbal Hallucinations into Therapy: Using Real-time fMRI-Neurofeedback to Treat Voices. Fovet, T., Orlov, N., Dyck, M., et al.[2020]

A new rtfMRI neurofeedback method targeting brain connectivity in areas related to mental disorders, like schizophrenia, was tested in a study with 38 healthy participants, showing strong links between brain connectivity and breathing patterns.

The study found that controlling for respiratory artefacts is crucial for accurate results in rtfMRI neurofeedback, with global signal regression (GSR) proving to be the most effective method for correcting these artefacts during real-time data analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Just a very expensive breathing training? Risk of respiratory artefacts in functional connectivity-based real-time fMRI neurofeedback. Weiss, F., Zamoscik, V., Schmidt, SNL., et al.[2021]

Neurofeedback (NF) using real-time fMRI shows promise in reducing the severity of auditory verbal hallucinations (AVHs) in three patients with treatment-resistant schizophrenia, as they learned to self-regulate activity in the anterior cingulate cortex (ACC).

While all patients reported some subjective improvement in AVH symptoms and mood during NF training, individual responses varied, highlighting the need for personalized approaches in future NF studies to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Treatment-Resistant Auditory Verbal Hallucinations in Schizophrenia with fMRI-Based Neurofeedback - Exploring Different Cases of Schizophrenia. Dyck, MS., Mathiak, KA., Bergert, S., et al.[2020]

In a study involving 10 schizophrenia patients with pharmacology-resistant auditory hallucinations, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB) effectively taught them to modulate brain activity in the superior temporal gyrus, leading to a significant reduction in hallucination scores.

A single 21-minute session of rt-fMRI NFB resulted in decreased activation of the superior temporal gyrus when ignoring a stranger's voice, indicating that this non-invasive technique could be a promising alternative treatment for those suffering from persistent auditory hallucinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction: Part 1: Superior temporal gyrus -Preliminary evidence. Okano, K., Bauer, CCC., Ghosh, SS., et al.[2023]

A meta-analysis of 31 clinical trials on neurofeedback using real-time fMRI (RT-fMRI-NF) showed significant improvements in depressive symptoms, with large effect sizes both immediately after training (g = 0.81) and at follow-up (g = 1.19).

While RT-fMRI-NF demonstrated medium effects on anxiety (g = 0.44) and emotion regulation (g = 0.48), the overall effectiveness in managing psychiatric symptoms is still uncertain due to high variability among studies, indicating a need for more rigorous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback as a new treatment for psychiatric disorders: A meta-analysis. Pindi, P., Houenou, J., Piguet, C., et al.[2022]

Patients with schizophrenia and auditory verbal hallucinations (AVH) were able to successfully down-regulate activity in the left posterior superior temporal gyrus (STG) using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) over a 2-week training period involving four MRI sessions.

Post-training, there was an increase in functional connectivity between the left STG and other speech-related brain regions, which correlated with a reduction in AVH symptoms, suggesting that rtfMRI-NF could be a promising therapeutic approach for managing AVH in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback to down-regulate superior temporal gyrus activity in patients with schizophrenia and auditory hallucinations: a proof-of-concept study. Orlov, ND., Giampietro, V., O'Daly, O., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Translating Neurocognitive Models of Auditory-Verbal Hallucinations into Therapy: Using Real-time fMRI-Neurofeedback to Treat Voices. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Just a very expensive breathing training? Risk of respiratory artefacts in functional connectivity-based real-time fMRI neurofeedback. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting Treatment-Resistant Auditory Verbal Hallucinations in Schizophrenia with fMRI-Based Neurofeedback - Exploring Different Cases of Schizophrenia. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction: Part 1: Superior temporal gyrus -Preliminary evidence. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback as a new treatment for psychiatric disorders: A meta-analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback to down-regulate superior temporal gyrus activity in patients with schizophrenia and auditory hallucinations: a proof-of-concept study. [2022]