Neurofeedback for Depression

Overseen By Lisa Stupar

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Kymberly Young

Must be taking: Antidepressants

Must not be taking: Antipsychotics, Anticonvulsants, Stimulants, others

Disqualifiers: Cardiovascular, Substance use, Brain injury, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to assist individuals with major depressive disorder using brain feedback technology. Participants engage in sessions designed to boost positive emotions by focusing on happy memories while receiving real-time feedback on their brain activity. The trial includes two groups: one receiving real feedback (Amygdala real-time fMRI neurofeedback) and the other viewing feedback from another participant for comparison. Suitable candidates for this trial have major depressive disorder, are currently experiencing depression, and either aren't on medication or are stable on an antidepressant. As an unphased trial, this study offers a unique opportunity to explore innovative treatment options for depression.

Will I have to stop taking my current medications?

If you are stable on an antidepressant, you can continue taking it during the study. However, if you are taking antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications that might affect brain blood flow, you may need to stop them at least 3 weeks before participating.

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

Research has shown that real-time brain scans used to provide feedback on the amygdala have been safely tested in both healthy individuals and those with depression. In these studies, participants learned to boost brain activity by recalling positive memories. This approach has, in some cases, reduced symptoms of depression.

The method's safety appears promising. Reviews of several studies have not identified major safety issues or harmful effects from the feedback process itself. Participants generally tolerate it well, suggesting it might be a safe option for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about amygdala real-time fMRI neurofeedback for depression because it offers a unique approach compared to traditional treatments like antidepressants and psychotherapy. Unlike these standard options, this method uses real-time brain imaging to help patients actively regulate their own brain activity, specifically in the amygdala, which is linked to emotions. By empowering individuals to upregulate their amygdala during positive autobiographical memory recall, this technique may provide a more personalized and immediate way to improve mood and emotional well-being. Plus, it offers a non-invasive alternative that doesn't rely on medication, which can be appealing to those who experience side effects from drugs.

What evidence suggests that amygdala real-time fMRI neurofeedback is effective for depression?

This trial will compare two approaches: Amygdala real-time fMRI neurofeedback and Sham feedback. Studies have shown that using real-time brain scans for feedback can aid individuals with depression. This technique enables control over brain activity, particularly in the amygdala, which governs emotions. Research indicates that this method can reduce depressive symptoms by training the brain to respond more effectively to positive memories. Specifically, one study found that depressive symptoms improved for up to 12 weeks after using this feedback technique. Another study confirmed the amygdala's key role in recovering from depression. Overall, early findings suggest that this approach could be a promising treatment for major depressive disorder. ^{1 2 6 7 8}

Who Is on the Research Team?

Kymberly Young, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with Major Depressive Disorder (MDD) who are either not on medication or have been stable on antidepressants for at least 4 weeks. Participants must be able to consent and complete questionnaires in English. Those with unstable health conditions, pregnant or breastfeeding women, individuals taking certain medications like antipsychotics or stimulants, and those with severe substance use disorders cannot join.

Inclusion Criteria

I have been diagnosed with major depression and am currently feeling depressed.

Able to give written informed consent prior to participation

I am not on antidepressants or have been stable on them for at least 4 weeks.

Exclusion Criteria

I have been diagnosed with a psychotic, bipolar, or organic mental disorder.

I have eye problems or trouble seeing even with glasses or contacts.

I cannot fill out forms in English.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two rtfMRI-nf sessions, one week apart, to increase amygdala response to positive memories

2 weeks

2 visits (in-person)

Follow-up

Participants complete the BDI-II monthly for one year following completion of the neurofeedback intervention

12 months

Monthly assessments (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Amygdala real-time fMRI neurofeedback
• Sham feedback

Trial Overview The study tests if a type of brain scan feedback called rtfMRI-nf can help people by increasing the amygdala's response to positive memories as a treatment for depression. Participants will receive either actual neurofeedback or sham (fake) feedback as part of the study.

How Is the Trial Designed?

Group I: Amygdala real-time fMRI neurofeedback Experimental Treatment 1 Intervention

Amygdala neurofeedback - attempt to upregulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Two sessions will be performed one week apart.

Group II: Sham feedback Placebo Group 1 Intervention

Yoked sham - participants will see the amygdala activity of another subject who completed the intervention. Two sessions will be performed one week apart.

Who Is Running the Clinical Trial?

Kymberly Young

Lead Sponsor

Trials

4

Recruited

440+

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Healthy individuals can learn to self-regulate the activity of the amygdala using real-time fMRI neurofeedback, leading to significant increases in blood oxygen level dependent (BOLD) signals during training.

This training not only enhances amygdala activation but also improves functional connectivity within a broader brain network, indicating potential therapeutic applications for neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-regulation of amygdala activation using real-time FMRI neurofeedback. Zotev, V., Krueger, F., Phillips, R., et al.[2021]

Training patients with major depressive disorder to enhance their amygdalar responses to positive memories using real-time fMRI neurofeedback led to increased amygdalar activity when viewing happy faces and decreased activity for sad faces, indicating a shift in emotional processing.

The training also improved participants' ability to identify positive emotional stimuli and reduced their reaction times to positive faces, suggesting that this neurofeedback approach may have effects similar to those of antidepressant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder. Young, KD., Misaki, M., Harmer, CJ., et al.[2019]

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]

The study demonstrated that healthy participants could effectively down-regulate activity in the right amygdala using real-time functional MRI (rtfMRI) neurofeedback while exposed to negative emotional stimuli, suggesting a potential method for emotion regulation.

This approach, which involved four training sessions with six participants, indicates that rtfMRI neurofeedback could be a promising tool for treating emotional disorders by targeting the overactive amygdala, which is often dysregulated in such conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time neurofeedback using functional MRI could improve down-regulation of amygdala activity during emotional stimulation: a proof-of-concept study. Brühl, AB., Scherpiet, S., Sulzer, J., et al.[2021]

Real-time fMRI neurofeedback (rtfMRI NF) allows individuals to voluntarily down-regulate the amygdala, which is linked to improved connectivity with the ventromedial prefrontal cortex (vmPFC) during emotional processing, as shown in a study with 16 healthy participants.

The study suggests that this increased connectivity may enhance emotion regulation, indicating that rtfMRI NF could be a promising tool for helping patients with severe emotion dysregulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity. Paret, C., Ruf, M., Gerchen, MF., et al.[2017]

Real-time functional MRI neurofeedback (rtfMRI-nf) training has shown promise in helping individuals, both healthy and those with depression, to regulate brain activity in the amygdala, which may enhance positive memory recall.

While initial studies indicate that rtfMRI-nf could help alleviate symptoms of major depressive disorder, further research with larger participant groups is needed to confirm its effectiveness as a clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: A review. Young, KD., Zotev, V., Phillips, R., et al.[2020]

In a study involving 35 adults with major depressive disorder, real-time fMRI neurofeedback (rtfMRI-nf) training to enhance amygdala responses during positive memory recall led to significant reductions in depressive symptoms and higher remission rates at 6 months and 1 year follow-up compared to a control group.

The combination of rtfMRI-nf and cognitive behavioral therapy (CBT) encouraged participants to focus more on positive thoughts and behaviors, suggesting that this approach may enhance the effectiveness of standard CBT in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression. Compère, L., Siegle, GJ., Riley, E., 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/PMC6035103/

Amygdala Real-Time fMRI Neurofeedback for Major ... In this review, we summarize the results of several studies that have developed and applied neurofeedback training to healthy and depressed individuals with ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0005796724000500

Amygdala real-time fMRI neurofeedback upregulation in ... Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial ...

3. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2017.16060637

Randomized Clinical Trial of Real-Time fMRI Amygdala ... These data support a role of the amygdala in recovery from depression. Depression is a common and disabling condition (1). With ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02709161

Effects of Amygdala Neurofeedback on Depressive ... The purpose of this study is to determine the clinical efficacy of augmenting cognitive-behavioral therapy with real-time functional magnetic resonance imaging ...

5. nature.com nature.com/articles/s41398-025-03382-8

a systematic review of real-time fMRI neurofeedback ... Previous studies have demonstrated that this approach allows individuals to gain self-regulation of most brain regions, including the amygdala [ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7724376/

A systematic review of fMRI neurofeedback reporting and ... Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder.

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A randomised controlled trial of amygdala fMRI ... BrainSTEADy, which aims to test whether amygdala-fMRI-neurofeedback specifically reduces emotion instability in BPD beyond nonspecific benefit.

8. 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.