Neurofeedback for Depression

Recruiting at 1 trial location

Overseen By Yael Jacob

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: CNS active medications

Disqualifiers: Schizophrenia, Psychotic disorders, Substance use, others

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

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help people with major depressive disorder (MDD) by reducing repetitive negative thinking, known as rumination. It uses a special type of brain training called Network Neurofeedback (also known as Neurofeedback Therapy or EEG Neurofeedback) to adjust brain activity linked to these thought patterns. Participants will receive either real-time feedback on their brain activity or a sham (placebo-like) version. This trial may suit those experiencing a depressive episode who struggle with frequent negative thoughts. As an unphased trial, it offers a unique opportunity to explore innovative treatments for MDD.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that affect the central nervous system at least one week before the MRI scan.

What prior data suggests that this neurofeedback protocol is safe for patients with major depressive disorder?

Research shows that real-time fMRI neurofeedback is generally well-tolerated. Studies have found that this therapy can help with various conditions, including depression. For example, one study found that it significantly improved symptoms in patients with major depressive disorder (MDD).

These studies have reported no major serious side effects, suggesting that the treatment is safe for most people. However, like any treatment, some individuals might experience mild discomfort, such as tiredness after a session. This is common with many types of therapy and usually not a cause for concern.

Overall, evidence suggests that fMRI neurofeedback is a promising and safe option for those seeking new ways to manage depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about network neurofeedback for depression because it offers a unique approach by using real-time brain activity data to potentially rewire brain patterns. Unlike standard depression treatments, which often rely on medication or talk therapy, network neurofeedback is non-invasive and focuses on the brain's own activity to promote mental health. This technique specifically targets the MOFC-precuneus connection, which is believed to play a key role in mood regulation. By providing immediate feedback based on the individual's brain activity, it could help patients achieve faster and more personalized results compared to traditional treatments.

What evidence suggests that this neurofeedback protocol is effective for reducing rumination in depression?

Research has shown that fMRI-based neurofeedback can help people with depression by altering brain function and improving connections between different brain areas. Studies have found that this technique might reduce repetitive negative thinking, common in depression. In this trial, participants in the Active Neurofeedback arm will receive real-time data depicting their own MOFC-precuneus brain activity while in the scanner. One study discovered that real-time fMRI neurofeedback led to greater improvement in patients compared to traditional treatments. This method targets specific brain areas involved in negative thoughts, aiming to enhance their positive effects. While more research is needed, early results are promising for those seeking new treatment options. ^{2 4 6 7 8}

Who Is on the Research Team?

Yael Jacob

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with major depressive disorder currently experiencing a depressive episode. They must understand English well enough to consent and participate in the study. Excluded are those with unstable medical conditions, recent CNS-active meds use, pregnancy, high suicide/homicide risk, involuntary psychiatric admission, active substance abuse within 6 months, or history of certain mental disorders.

Inclusion Criteria

Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process

Exclusion Criteria

Any current or history of schizophrenia or other psychotic disorder, neurodevelopmental disorder, or neurocognitive disorder for patients, active substance use disorder within the past 6 months

Pregnancy

I haven't taken any brain-affecting meds in the last week and don't have unstable health issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neurofeedback Treatment

Participants receive real-time fMRI neurofeedback to up-regulate MOFC influence on the precuneus

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in rumination and depressive symptoms

30 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Network Neurofeedback

Trial Overview The trial tests a new neurofeedback technique using high-resolution MRI to reduce rumination in depression by enhancing brain connectivity between specific regions. Participants will receive real-time feedback from an MRI machine to potentially modulate their brain activity more precisely than traditional methods.

How Is the Trial Designed?

Group I: Active Neurofeedback Active Control 1 Intervention

Participants randomized to Active neurofeedback will receive real-time data depicting MOFC-precuneus brain activity while in the scanner.

Group II: Sham Neurofeedback Placebo Group 1 Intervention

Participants randomized to the Sham neurofeedback control group will receive the feedback of a prior scanned participant's active MOFC-precuneus up-regulation and not their own brain activity. This condition will still visually resemble the active conditions.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

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 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]

A study involving 608 participants across 28 experiments found that including a pre-training no-feedback run significantly improves neurofeedback performance, likely by helping participants become familiar with the setup and tasks.

Patients showed better neurofeedback performance than healthy participants, possibly due to higher motivation and the need to regulate dysfunctional brain signals, suggesting that tailoring neurofeedback interventions for clinical populations could enhance their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis. Haugg, A., Renz, FM., Nicholson, AA., et al.[2021]

A novel closed-loop neurofeedback procedure was tested on 15 participants with major depressive disorder and 12 healthy controls, showing that it can help reduce negative attentional bias in those with depression.

Participants with major depressive disorder experienced a decrease in depression severity after neurofeedback training, suggesting this technique could be a promising treatment for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cloud-Based Functional Magnetic Resonance Imaging Neurofeedback to Reduce the Negative Attentional Bias in Depression: A Proof-of-Concept Study. Mennen, AC., Turk-Browne, NB., Wallace, G., et al.[2022]

In a proof-of-concept study involving eight patients with depression, those who used fMRI-based neurofeedback to enhance brain activity in areas linked to positive emotions showed significant improvement in their depression symptoms, as measured by the Hamilton Rating Scale for Depression.

A control group that practiced the same cognitive strategies without neurofeedback did not experience any clinical improvement, suggesting that the neurofeedback technique may be a promising new approach for enhancing treatment outcomes in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time self-regulation of emotion networks in patients with depression. Linden, DE., Habes, I., Johnston, SJ., et al.[2022]

A real-time fMRI neurofeedback system was developed to help patients with depression achieve a 'happiness emotional brain state' by training them to match their neural activity to that of a healthy participant, showing improvements in classifier accuracy and clinical symptoms after 4 training sessions over 2 weeks.

Seven female patients with mild to moderate depression experienced significant clinical improvements, as measured by standardized evaluations and self-reports, which persisted even 10 days after the intervention, indicating potential for this noninvasive approach in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-time fMRI neurofeedback system for the clinical alleviation of depression with a subject-independent classification of brain states: A proof of principle study. Pereira, JA., Ray, A., Rana, M., et al.[2022]

In a study of 20 drug-free patients with mild to moderate depression, both real-time fMRI neurofeedback and cognitive behavioral therapy (CBT) were effective in reducing depressive symptoms, but neurofeedback was not found to be superior to CBT.

The neurofeedback group showed a continuous improvement in self-regulation skills over the treatment sessions, indicating a potential learning effect, while a trend suggested that CBT might lead to greater overall improvement in depression symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback compared to cognitive behavioral therapy in a pilot study for the treatment of mild and moderate depression. Mel'nikov, MY., Bezmaternykh, DD., Savelov, AA., et al.[2023]

Real-time fMRI can help patients learn to self-regulate brain circuits related to emotion and depression, showing promise as a new approach to treating affective disorders.

Initial results from fMRI-based neurofeedback (fMRI-NF) in depression are encouraging, but further clinical trials are needed to establish its efficacy and to develop practical applications for everyday use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback and networks of depression. Linden, DE.[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]

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]

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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