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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to develop a technique called real time fMRI neurofeedback. This technique uses a regular MRI scanner, except that special software allows the researchers to measure activity in participants brain, using fMRI, and then give information, in the form of a feedback signal, which indicates brain activity in real time, while in the MRI scanner. The larger goal of this study is to develop ways to help people, including those with depression, better regulate brain activity. The researchers think that this may be helpful in managing psychiatric symptoms. This study design has three phases, however, only two phases (phase 2 and 3) are considered to be a clinical trial. Phase 2 (part 2) was registered and is NCT05934604. This is the phase 3 (part 3) for this project and is funded by the National Institutes of Health.

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 data supports the effectiveness of the treatment fMRI Neurofeedback for Depression?

Research suggests that real-time fMRI neurofeedback (rt-fMRI NF) may help people with depression by allowing them to control brain areas linked to emotions. Some studies show it can change brain activity patterns, but more research is needed to confirm its effectiveness and long-term benefits. ^{1 2 3 4 5}

Is fMRI neurofeedback safe for humans?

Research on fMRI neurofeedback, including studies on depression, suggests it is generally safe for humans. However, more studies are needed to fully understand its long-term effects and any potential adverse effects. ^{2 3 4 5 6}

How does the treatment fMRI Neurofeedback for Depression differ from other treatments for this condition?

fMRI Neurofeedback for Depression is unique because it uses real-time brain imaging to provide feedback, helping patients learn to regulate specific brain areas associated with emotion processing, unlike traditional treatments that do not involve direct brain activity monitoring. ^{1 2 3 4 6}

Research Team

Stephan Taylor, MD

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. Switzerland 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. [2022]

2. United States 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Time fMRI Neurofeedback Training as a Neurorehabilitation Approach on Depressive Disorders: A Systematic Review of Randomized Control Trials. [2022]

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

Clinical Application of Real-Time fMRI-Based Neurofeedback for Depression. [2021]

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

Connectivity based Real-Time fMRI Neurofeedback Training in Youth with a History of Major Depressive Disorder. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Guide to Literature Informed Decisions in the Design of Real Time fMRI Neurofeedback Studies: A Systematic Review. [2020]