Neurofeedback for Depression

Overseen By Frederick Nitchie

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must not be taking: Psychoactive medications

Disqualifiers: Pregnancy, Neurological disorder, Alcohol abuse, others

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

Compensation: Varies

Number of Visits: Unknown

34 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new therapy that uses brain scans to help patients with depression change their focus from negative to positive. It targets people with Major Depressive Disorder who often dwell on negative thoughts. The therapy provides real-time feedback and adjusts tasks to reduce negative focus.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any psychoactive medications, including antidepressants, to participate in this trial.

What data supports the effectiveness of the treatment Active Closed Loop Real Time fMRI Neurofeedback for depression?

Research shows that patients with depression who used real-time fMRI neurofeedback to regulate brain areas linked to positive emotions experienced significant improvements in their symptoms. However, more studies are needed to confirm these findings and rule out placebo effects. ^{1 2 3 4 5}

Is neurofeedback using real-time fMRI safe for humans?

Real-time fMRI neurofeedback has been used in studies with patients experiencing depression, showing promising results without reported safety concerns. However, more research is needed to confirm its safety and effectiveness across larger groups and different conditions. ^{1 2 3 6 7}

How does the treatment Active Closed Loop Real Time fMRI Neurofeedback differ from other treatments for depression?

This treatment is unique because it uses real-time brain imaging to help patients learn to regulate their own brain activity, specifically targeting areas involved in emotion processing. Unlike traditional therapies that rely on medication or talk therapy, this approach provides immediate feedback to patients, allowing them to practice achieving a healthier brain state during the sessions. ^{1 2 3 4 7}

Research Team

Yvette I Sheline, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

Adults aged 18-65 with Major Depressive Disorder (MDD) as per DSM-5, scoring at least 16 on the MADRS scale for depression severity. Participants must have normal cognition, understand English, and consent to join. Excluded are pregnant women, those outside the age range or with MRI contraindications like metal implants or claustrophobia, neurological issues affecting brain data or causing depression, recent substance abuse, non-correctable vision loss, active suicide risk or current psychoactive medication use.

Inclusion Criteria

I am between 18 and 65 years old and have been diagnosed with major depressive disorder.

Participants must be able to read and understand English

Scoring at least a minimum score of 16 on Montgomery Asberg Depression Rating Scale (MADRS)

Exclusion Criteria

I am currently taking medication for my mental health or am in therapy.

Pregnancy (female participants)

Refusal to provide informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

R61 Phase

Participants undergo four training sessions with either active or sham neurofeedback, each session lasting 32 minutes

4 sessions

R33 Phase

Number of training sessions are contingent on R61 findings, involving either active or sham neurofeedback

Contingent on R61 findings

Follow-up

Participants are monitored for changes in depression severity and attentional mechanisms

5 years

Treatment Details

Interventions

• Active Closed Loop Real Time fMRI Neurofeedback
• Sham Closed Loop Real Time fMRI Neurofeedback

Trial Overview The trial is testing a new therapy using real-time fMRI neurofeedback aimed at reducing negative attention bias in MDD patients. It involves decoding a patient's attentional state and adjusting task stimuli accordingly. The study compares actual neurofeedback against sham feedback to determine its effectiveness.

Participant Groups

Group I: Active Neurofeedback Active Control 1 Intervention

R61 Phase: Four training sessions. Each training session contains 32 minutes of active neurofeedback runs. R33 Phase: Number of training sessions are contingent on R61 findings.

Group II: Sham Neurofeedback Placebo Group 1 Intervention

R61 Phase: Four training sessions. Each training session contains 32 minutes of sham (placebo) neurofeedback runs. R33 Phase: Number of training sessions are contingent on R61 findings.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

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]

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 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]

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]

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

Individual- and Connectivity-Based Real-Time fMRI Neurofeedback to Modulate Emotion-Related Brain Responses in Patients with Depression: A Pilot Study. [2022]

5. 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]

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

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

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

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