fMRI Neurofeedback for Depression

Overseen By Stephan Taylor, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must be taking: Antidepressants

Disqualifiers: Bipolar, Schizophrenia, OCD, others

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

Compensation: Varies

Number of Visits: 3

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new technique using an MRI scanner to help people with depression regulate their brain activity. Participants receive real-time feedback on their brain activity during an fMRI scan, which might help manage psychiatric symptoms. There are two groups: one receives actual feedback (fMRI with real-time feedback), and the other receives placebo-like feedback (fMRI with sham-controlled feedback). This trial suits individuals diagnosed with Major Depressive Disorder who have been stable on medication, if any, for four weeks and can handle small spaces without anxiety. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve future depression treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on antidepressants, you must be on a stable dosage for at least 4 weeks before participating.

What prior data suggests that this fMRI neurofeedback technique is safe for use in humans?

Research shows that real-time fMRI neurofeedback has been explored for its impact on the brain and behavior in people with mental health conditions. This technique uses an MRI machine to display brain activity in real-time, helping individuals learn to manage their brain patterns.

Studies have not identified any major safety concerns with this method. Participants generally handle it well, and there have been no significant reports of harmful side effects. It resembles a regular MRI, which is a safe and common medical procedure.

So far, real-time fMRI neurofeedback appears safe for people. However, more research is needed to fully understand its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about fMRI neurofeedback for depression because it offers a new, non-invasive way to potentially manage symptoms by allowing patients to see and learn to control their brain activity in real time. Unlike traditional treatments that often rely on medication or talk therapy, this approach uses advanced imaging technology to provide immediate feedback, helping individuals recognize and modify thought patterns associated with depression. The use of real-time feedback is particularly promising as it empowers patients to actively participate in their mental health care, potentially leading to faster and more personalized treatment outcomes.

What evidence suggests that this fMRI neurofeedback technique is effective for depression?

Research shows that real-time fMRI neurofeedback, a treatment in this trial, may help people with depression. Studies have found that this method can significantly reduce depression symptoms. In one study, participants who received real-time feedback showed substantial improvement later on. This technique uses brain scans to provide immediate information, helping individuals learn to control their brain activity. Evidence suggests it could be an effective option for those who haven't responded well to other treatments. Overall, early research is hopeful about its potential for managing depression. Participants in this trial may receive either real-time neurofeedback or sham-controlled feedback to evaluate the effectiveness of this approach. ^{1 2 4 6 7}

Who Is on the Research Team?

Stephan Taylor, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for adults with Major Depressive Disorder who are not pregnant, can handle small spaces without anxiety, have been on a stable antidepressant dose for 4 weeks, and don't have metal implants that affect MRI scans. They must also be of a size to fit in the scanner and willing to consent. Participants should not have serious neurological issues or certain psychiatric conditions like bipolar disorder.

Inclusion Criteria

You have no metals, implants or metallic substances on your body that could be affected by a strong magnetic field or interfere with imaging.

Your size must be suitable for scanning with the gantry.

I have been on a stable dose of antidepressants for at least 4 weeks.

Exclusion Criteria

I have no serious brain-related health issues or conditions like liver failure that could affect my brain.

I have never had a severe head injury.

I do not have bipolar disorder, schizophrenia, OCD, an active eating disorder, or PTSD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Assessment and Training

Participants undergo initial assessment and training, including practice tasks using a mock scanner

1 week

1 visit (in-person)

Neurofeedback Training

Participants complete real-time fMRI neurofeedback sessions to practice tasks and measure brain activity

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in brain activity and psychiatric symptoms after neurofeedback training

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FMRI with real time feedback
• FMRI with sham controlled feedback

Trial Overview

The study tests real-time fMRI neurofeedback versus sham feedback to help manage depression by teaching participants to regulate brain activity. It's part of a larger project funded by the National Institutes of Health and follows an earlier phase (NCT05934604).

How Is the Trial Designed?

Group I: Real-time neurofeedback Experimental Treatment 1 Intervention

Subjects will complete three visits with one or two fMRI sessions after initial assessment and training visit. The first session will be to introduce practice tasks using the mock scanner. In the second visit participants will have an fMRI. The study team will review the fMRI results to decide if participants will continue on the study (must exhibit a specific pattern of activation) and have the second fMRI at the third visit.

Group II: Sham controlled feedback Placebo Group 1 Intervention

Subjects will complete three visits with one or two fMRI sessions after initial assessment and training visit. The first session will be to introduce practice tasks using the mock scanner. In the second visit participants will have an fMRI. The study team will review the fMRI results to decide if participants will continue on the study (must exhibit a specific pattern of activation) and have the second fMRI at the third visit.

FMRI with real time feedback is already approved in United States, European Union for the following indications:

Approved in United States as Real-time fMRI Neurofeedback for:

• Depression
• Psychiatric symptoms management

Approved in European Union as rt-fMRI NF for:

• Depression
• Emotional dysregulation

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Real-time functional magnetic resonance imaging-based neurofeedback (rt-fMRI-NF) shows promise in altering brain activity and reducing symptoms of depression, but most studies have focused on healthy participants rather than clinical populations.

The review suggests that future rt-fMRI-NF studies should incorporate better feedback methods, use clinical samples, and include appropriate control groups to enhance the reproducibility and effectiveness of neurofeedback interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Guide to Literature Informed Decisions in the Design of Real Time fMRI Neurofeedback Studies: A Systematic Review. Fede, SJ., Dean, SF., Manuweera, T., et al.[2020]

Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) shows a medium-sized effect on neural activity during training and a large effect on neural activity after training, indicating its potential to influence brain function in psychiatric disorders.

Behavioral outcomes from rtfMRI-NF, such as symptom reduction, show a small effect size, suggesting that while rtfMRI-NF can impact brain activity, its effects on behavior may be less pronounced and require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of real-time functional magnetic resonance imaging neurofeedback for psychiatric illness: A meta-analysis of brain and behavioral outcomes. Dudek, E., Dodell-Feder, D.[2022]

In a study involving 10 individuals with a history of major depressive disorder (MDD) and 12 healthy controls, real-time fMRI neurofeedback (rtfMRI-nf) targeting the connectivity between the amygdala and prefrontal regions showed potential for enhancing emotional regulation, particularly in healthy individuals who exhibited increased frontal cortex activation during training.

Participants with a history of MDD demonstrated a trend towards decreased functional connectivity over the training runs, and while the overall group experienced a reduction in negative emotions, the MDD group specifically showed a significant decrease in positive emotions after the neurofeedback sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Connectivity based Real-Time fMRI Neurofeedback Training in Youth with a History of Major Depressive Disorder. He, X., Moreno, DR., Hou, Z., et al.[2023]

In a pilot study involving 16 patients with major depressive disorder (MDD) and 19 healthy controls, real-time functional MRI neurofeedback (rtfMRI NF) training showed changes in brain connectivity, particularly between the insula and dorsolateral prefrontal cortex, indicating potential neurobiological impacts of the intervention.

Despite these neurobiological changes, the rtfMRI NF training did not lead to significant improvements in depressive symptoms as measured by psychometric scores, suggesting that while the technique may influence brain activity, it may not yet translate to clinical efficacy in symptom reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual- and Connectivity-Based Real-Time fMRI Neurofeedback to Modulate Emotion-Related Brain Responses in Patients with Depression: A Pilot Study. Maywald, M., Paolini, M., Rauchmann, BS., et al.[2022]

Real-time functional magnetic resonance imaging-based neurofeedback (rt-fMRI NF) is a promising technique for treating depression by training individuals to self-regulate brain areas like the amygdala, which is often overactive in response to negative stimuli.

Initial randomized controlled trials show promising results for rt-fMRI NF in improving emotional processing, but further research is needed to determine the best methods, target regions, and training durations for lasting clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Application of Real-Time fMRI-Based Neurofeedback for Depression. Mathiak, K., Keller, M.[2021]

A systematic review of 11 reports from four randomized control trials found that real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-nf) training showed a tendency to improve clinical depression scores, but the overall effect was not statistically significant (SMD -0.32).

While changes in brain activation patterns were observed after rt-fMRI-nf training, the evidence regarding its effectiveness for treating clinical depression remains of low certainty, indicating that more high-quality studies are needed to assess its impact on quality of life and other outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time fMRI Neurofeedback Training as a Neurorehabilitation Approach on Depressive Disorders: A Systematic Review of Randomized Control Trials. González Méndez, PP., Rodino Climent, J., Stanley, JA., et al.[2022]

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