Neurofeedback for Depression

(CNF-RNT Trial)

Overseen By Aki Tsuchiyagaito, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Laureate Institute for Brain Research, Inc.

Must not be taking: Cardiovascular, Psychotropic, others

Disqualifiers: Traumatic brain injury, Cardiovascular, Psychosis, Schizophrenia, Substance use, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to assist individuals with major depressive disorder (MDD) who frequently experience negative thinking patterns. Researchers use a technique called real-time fMRI neurofeedback, which provides feedback signals to the brain to help alter connections in specific brain areas. Participants are divided into two groups: one receives real feedback (active neurofeedback), while the other receives fake feedback (sham neurofeedback) for comparison. This trial targets young adults diagnosed with MDD who struggle with repetitive negative thoughts. Those who have experienced depression and often brood may find this trial suitable. As an unphased trial, it offers a unique opportunity to contribute to innovative research and potentially benefit from cutting-edge treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot start new psychotropic medications or therapy for depression or anxiety less than a month before joining. Also, you cannot use more than three psychotropic medications or certain cardiovascular medications.

What prior data suggests that real-time fMRI neurofeedback is safe for treating depression?

Research has shown that real-time fMRI neurofeedback is generally well-tolerated. Studies have found this feedback to be safe for treating mental health conditions like depression. Most research comparing real neurofeedback to sham treatments has identified no major safety concerns. Participants typically manage the treatment well, with few reporting significant side effects. This suggests that the neurofeedback used in this trial is typically safe for individuals with major depressive disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about neurofeedback for depression because it offers a non-invasive way to potentially improve mental health by directly targeting brain activity. Unlike traditional treatments like antidepressants or therapy, which often require time to show effects, neurofeedback provides immediate feedback on brain function, helping individuals recognize and modify their repetitive negative thought patterns. This approach could lead to faster symptom relief by enhancing the brain's connectivity in real-time, offering a novel mechanism of action compared to existing options.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that real-time brain activity feedback, known as rtfMRI-nf, holds promise for treating depression. In this trial, participants will receive either Active neurofeedback, which provides feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity, or Sham neurofeedback, which provides artificially generated feedback signals. In one study, 75% of participants reported feeling better four weeks after treatment. Another study found that up to 100% of people with major depression showed behavioral improvements. These results suggest that this type of feedback may help reduce negative thinking in depression by altering brain connectivity. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for young adults with major depressive disorder (MDD) who often have repetitive negative thoughts. Participants must be within a certain age range, typically considered 'young adult', and should meet specific criteria for MDD and high levels of such thoughts.

Inclusion Criteria

I am able to understand and willing to sign a consent form.

I have been diagnosed with major depression according to DSM-5.

I often find myself dwelling on my problems.

Exclusion Criteria

Current psychosis

Severe claustrophobia

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo real-time fMRI neurofeedback sessions to modulate brain connectivity related to repetitive negative thinking

1 week

2 visits (in-person)

Follow-up

Participants are monitored for changes in functional connectivity and depression severity

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Active neurofeedback
• Sham neurofeedback

Trial Overview

The study tests if real-time fMRI neurofeedback can influence brain networks to reduce repetitive negative thinking in depression. It's a randomized trial comparing active neurofeedback targeting specific brain areas versus sham (fake) feedback.

How Is the Trial Designed?

Group I: Active neurofeedback Experimental Treatment 1 Intervention

Receiving feedback signals from the repetitive negative thinking (RNT)-related brain functional connectivity

Group II: Sham neurofeedback Placebo Group 1 Intervention

Receiving artificially generated feedback signals.

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

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This study aimed to delineate the whole-brain mechanisms underpinning the effects of rtfMRI-NF on repetitive negative thinking in depression.

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