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

Trial Summary

What is the purpose of this trial?

The goal of this study is to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as a stand-alone intervention for major depressive disorder

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 data supports the effectiveness of the treatment Amygdala real-time fMRI neurofeedback for depression?

Research shows that real-time fMRI neurofeedback, which helps people learn to control their brain activity, can improve emotional control and reduce depressive symptoms by increasing positive memory recall. Studies suggest that this treatment can enhance the effectiveness of traditional therapies like cognitive behavioral therapy (CBT) for depression. ^{1 2 3 4 5}

Is neurofeedback using real-time fMRI safe for humans?

Research on real-time fMRI neurofeedback, including studies on healthy individuals and those with depression, suggests it is generally safe. The technique involves training people to control specific brain areas, like the amygdala, and has been used without significant safety concerns in various studies. ^{3 4 6 7 8}

How is the treatment 'Amygdala real-time fMRI neurofeedback' different from other treatments for depression?

This treatment is unique because it uses real-time brain imaging to help patients learn to control their brain activity, specifically targeting the amygdala, which is involved in emotional processing. Unlike traditional therapies, it provides immediate feedback on brain function, allowing patients to practice regulating their emotions in real-time. ^{1 2 3 4 8}

Research Team

Kymberly Young, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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. Australia pubmed.ncbi.nlm.nih.gov

Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: A review. [2020]

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

Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder. [2019]

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

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression. [2023]

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

Self-regulation of amygdala activation using real-time FMRI neurofeedback. [2021]

6. United States 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. [2021]

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

fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity. [2017]

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

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