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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with schizophrenia who experience auditory hallucinations (hearing voices) that do not improve with medication. The trial uses neurofeedback to teach participants to control specific brain areas linked to these hallucinations. Participants are divided into two groups: one receives real-time fMRI neurofeedback targeting the superior temporal gyrus (stg-rt-fMRI-Neurofeedback), a brain area involved in hearing, while the other receives sham feedback from a different brain area for comparison. Individuals diagnosed with schizophrenia or schizoaffective disorder who continue to experience auditory hallucinations despite medication may be suitable for this study. As an unphased trial, this study provides a unique opportunity to explore innovative treatment methods for those seeking alternatives to traditional medication.

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 prior data suggests that this neurofeedback intervention is safe for schizophrenia patients with auditory hallucinations?

Research has shown that real-time fMRI neurofeedback is generally safe for people. This non-invasive technique does not involve surgery or entering the body. Studies with patients who have schizophrenia have found it to be well-tolerated. For instance, one study provided feedback to the superior temporal gyrus (STG), which helped reduce symptoms like hearing voices. Another study demonstrated that this method can change brain activity without causing harm.

These studies have reported no serious side effects. Current data suggests the treatment's safety is promising. However, as with any new treatment, staying informed and consulting healthcare professionals is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about fMRI neurofeedback for schizophrenia with auditory hallucinations because it offers a novel approach by targeting brain activity directly. Unlike typical antipsychotic medications that alter neurotransmitter levels, this method allows patients to receive real-time feedback on their brain's superior temporal gyrus (STG) activity, potentially helping them gain control over their hallucinations. This technique could provide an alternative for patients who don't respond well to medication, and it offers a non-invasive option with fewer side effects. Additionally, the sham comparator group, receiving feedback from the motor cortex, helps ensure the effectiveness of this targeted neurofeedback. This innovative approach could revolutionize the way we treat auditory hallucinations in schizophrenia.

What evidence suggests that this trial's neurofeedback treatments could be effective for reducing auditory hallucinations in schizophrenia?

Research shows that using real-time fMRI neurofeedback to target the superior temporal gyrus (STG) can help reduce auditory hallucinations in people with schizophrenia. In this trial, participants in the STG-rt-fMRI arm will receive feedback from the STG. Studies have found that this feedback can help patients learn to control activity in this area, leading to fewer hallucinations and improved connections in brain areas related to hearing and other functions. One study found that this method can lower activity in the main hearing part of the brain, which may help reduce hallucination symptoms. Overall, these findings suggest that this treatment could be effective for those who do not respond to medication for hearing voices. Meanwhile, participants in the sham-rt-fMRI arm will receive feedback from the motor cortex, serving as a comparator to evaluate the effectiveness of the targeted STG approach. ^{1 3 6 7 8}

Who Is on the Research Team?

margaret niznikiewicz

Principal Investigator

Boston VA Research Institute, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

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Real-time fMRI feedback impacts brain activation, results in ... A single session of real-time fMRI neurofeedback significantly reduced activation in the superior temporal gyrus (STG) post neurofeedback.