Neurofeedback for Depression

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

Trial Summary

What is the purpose of this trial?

This trial helps patients with major depressive disorder reduce negative thinking. By observing their brain's function, patients can learn to change how their brain works, potentially reducing symptoms of depression.

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 data supports the effectiveness of the treatment Network Neurofeedback for depression?

Research shows that real-time fMRI neurofeedback, a type of brain training, can help people with depression improve their symptoms by teaching them to control brain areas linked to positive emotions. Studies have found that patients using this method showed significant improvement in depression symptoms compared to those who did not receive neurofeedback. ^{1 2 3 4 5}

Is neurofeedback safe for treating depression?

Current research on neurofeedback, including real-time fMRI neurofeedback, suggests it is generally safe for humans, but more studies are needed to fully understand its safety, especially regarding long-term effects and potential adverse reactions. ^{3 4 6 7 8}

How is the treatment Network Neurofeedback different from other treatments for depression?

Network Neurofeedback is unique because it uses real-time brain imaging to help patients learn to control specific brain areas linked to depression, like the amygdala, which is involved in emotion processing. Unlike traditional treatments, it focuses on self-regulation of brain activity through feedback, potentially offering a personalized approach to managing depressive symptoms. ^{3 4 9 10 11}

Research Team

Yael Jacob

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Pregnancy

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

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

Real-time self-regulation of emotion networks in patients with depression. [2022]

2. Switzerland 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Neurofeedback and networks of depression. [2021]

4. 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]

5. Germany 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. [2023]

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

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis. [2021]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

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

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

10. 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]

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

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