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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new therapy for individuals with major depressive disorder (MDD). It employs real-time brain imaging to help change participants' focus on negative thoughts, potentially reducing depression symptoms. Participants will receive either the actual neurofeedback sessions (Active Closed Loop Real Time fMRI Neurofeedback) or a placebo version (Sham Closed Loop Real Time fMRI Neurofeedback) for comparison. This study suits those diagnosed with depression who are not currently on antidepressants or in therapy and do not have conditions affecting brain function. Participants must understand English and be able to undergo MRI scans. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in mental health treatment.

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 prior data suggests that this neurofeedback technique is safe for treating depression?

Research has shown that real-time fMRI neurofeedback therapy is generally safe. This therapy involves monitoring brain activity and providing feedback to the patient. Studies have found it can be used without serious side effects. For instance, a review found it to be a safe option for those who do not respond well to traditional depression treatments. Other research indicates that this type of neurofeedback works better than some standard treatments without causing significant negative effects. Overall, evidence suggests that fMRI neurofeedback is well-tolerated and does not lead to major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using neurofeedback for depression because it offers a new, non-invasive way to potentially regulate brain activity. Unlike traditional treatments like antidepressant medications and psychotherapy, this technique uses real-time fMRI to provide feedback on brain function, helping patients consciously adjust their neural patterns. This innovative approach could provide a quicker, personalized method to manage depression, targeting specific brain regions involved in mood regulation. Additionally, the use of both active and sham neurofeedback helps determine the true effectiveness of neurofeedback, paving the way for more tailored interventions in mental health care.

What evidence suggests that this neurofeedback therapy is effective for depression?

Research has shown that real-time fMRI neurofeedback, a therapy that helps the brain change its activity to reduce depression, holds promise for treating major depressive disorder (MDD). In this trial, participants will join either the Active Neurofeedback arm or the Sham Neurofeedback arm. Studies have found that real-time fMRI neurofeedback can lessen negative attention bias, which often worsens depression. This method uses brain scans to assess a person's current mental state and then adjusts tasks to improve it. Early results suggest this approach can be effective, especially for those who haven't responded well to traditional treatments. Overall, past patients have demonstrated varied but positive responses, making it a hopeful option for managing depression. ^{1 2 6 7 8}

Who Is on the Research Team?

Yvette I Sheline, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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

Participants must be able to read and understand English

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

My thinking and memory skills are normal.

Exclusion Criteria

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

Pregnancy (female participants)

Refusal to provide informed consent

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Active Neurofeedback Active Control 1 Intervention

R61 Phase: Three 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: Three 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+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12264674/

Effectiveness of fMRI-based Neurofeedback Therapy on ... This systematic review explores the efficacy of fMRI-based neurofeedback as an alternative treatment for individuals with depression who do not respond well ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07159061

NCT07159061 | Neurofeedback to Treat Depression - 2 This real-time fMRI neurofeedback therapy uses cloud-based pattern classification to decode a patient's attentional state and dynamically modulate task stimuli ...

3. nature.com nature.com/articles/s41380-024-02880-3

Clinical response to neurofeedback in major depression ... This study investigated whole-brain response patterns during rtfMRI-NF training to explain interindividual variability in clinical efficacy in MDD.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05169346?tab=history&a=6

Record History | ver. 6: 2022-12-08 | NCT05169346 ... This study tests the efficacy of a new psychotherapeutic strategy for reducing negative attention bias (and therefore depression severity) in participants with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2451902224003112

Closed-Loop Systems and Real-Time Neurofeedback in ... In this review, we explore the use of closed-loop systems and real-time neurofeedback to influence, augment, or promote mindfulness interventions.

6. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/radiol.231143

Functional MRI Neurofeedback Outperforms Cognitive ... Real-time fMRI neurofeedback therapy led to a greater reduction in tinnitus distress than the current standard treatment of CBT.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763420306953

The efficacy of real-time functional magnetic resonance ... We present the first meta-analysis of rtfMRI-NF for psychiatric disorders, evaluating its impact on brain and behavioral outcomes.

8. withpower.com withpower.com/trial/phase-depression-10-2024-3611c

Meditative Neurofeedback for Depression (MediNF Trial) Research on neurofeedback, including Meditative Neurofeedback, suggests it is generally safe for humans, with studies showing it can be used without serious ...