Neurofeedback for Healthy Subjects

Overseen By Augustin C. Hennings, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Trustees of Princeton University

Must not be taking: Psychoactive drugs

Disqualifiers: Pregnancy, Psychiatric, Neurological, others

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

Compensation: Varies

Number of Visits: 4

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new behavioral treatment using real-time brain scans to understand and manage threat expectations. The treatment involves neurofeedback, where participants receive real-time feedback on their brain activity, focusing on the connection between the prefrontal cortex and the hippocampus. Participants will receive either actual neurofeedback (Active Real-time fMRI Neurofeedback) or a sham version to compare results. Suitable candidates are healthy adults with no history of brain or psychiatric disorders, not taking mind-altering medications, and able to undergo an MRI scan. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in understanding brain function and behavioral treatment.

Will I have to stop taking my current medications?

If you are currently taking psychoactive medication or drugs of abuse, you will need to stop taking them to participate in this trial.

What prior data suggests that this neurofeedback intervention is safe for healthy adults?

Research has shown that real-time fMRI neurofeedback is generally well-tolerated. This treatment uses brain scans to provide feedback, helping individuals learn to control certain brain activities. In about 25% to 50% of cases, participants successfully change their brain activity using this method.

Although information on side effects is limited, the technology is non-invasive, meaning it doesn't involve surgery or entering the body, and is usually considered safe. Most reports have not mentioned any serious side effects. However, as with any treatment, experiences can vary. Always discuss potential risks and benefits with the study team before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel way to enhance memory control using real-time fMRI neurofeedback. Unlike traditional methods that might involve medication or cognitive exercises, this technique directly influences brain activity by reinforcing specific neural connections between the dlPFC and hippocampus. By potentially increasing memory control ability through targeted neurofeedback, this approach offers a cutting-edge alternative to existing treatments.

What evidence suggests that this neurofeedback intervention is effective for reducing threat expectancy?

This trial will compare Active Real-time fMRI Neurofeedback with Sham Real-time fMRI Neurofeedback. Research has shown that real-time fMRI neurofeedback can calm overactive brain areas linked to memory, potentially improving memory function. Studies have found that this training can alter brain activity, particularly in regions associated with memory and emotions. The goal is to strengthen the connection between the prefrontal cortex and the hippocampus, enhancing memory control. This may improve the formation and recall of memories while reducing unwanted memories. Overall, early results suggest this method could effectively boost brain functions related to memory and threat response. ^{6 7 8 9 10}

Who Is on the Research Team?

Kenneth A. Norman, Ph.D.

Principal Investigator

Princeton University

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-50 who have no history of psychiatric or neurological disorders, are not on psychoactive medications or drugs, can undergo MRI scans (no metal implants), have normal color vision, are right-handed, show spontaneous recovery behavior in a test session, and fully understand English.

Inclusion Criteria

No history of psychiatric disorders or neurological disorders affecting the central nervous system

I am between 18 and 50 years old.

I am not taking any psychoactive medication or drugs.

Exclusion Criteria

Does not exhibit spontaneous recovery behavior as determined by an experimenter in a prescreening experimental session

I am currently taking medication for mental health or using recreational drugs.

I am unwilling to give my consent for participation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neurofeedback Intervention

Participants receive real-time fMRI neurofeedback to enhance memory control ability

Up to 8 weeks

4 fMRI sessions

Follow-up

Participants are monitored for changes in spontaneous recovery behavior and neurofeedback learning

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Active Real-time fMRI Neurofeedback
• Sham Real-time fMRI neurofeedback

Trial Overview The study is testing the effectiveness of real-time fMRI neurofeedback to reduce threat expectancy. Participants receive feedback based on brain activity between the prefrontal cortex and hippocampus. Some get actual feedback while others receive sham (fake) feedback as a comparison.

How Is the Trial Designed?

Group I: Active Neurofeedback Experimental Treatment 1 Intervention

Active neurofeedback will reinforce negative dlPFC-hippocampal functional connectivity, as this is expected to increase memory control ability.

Group II: Control Neurofeedback Placebo Group 1 Intervention

Participants in the control neurofeedback group will receive the same instructions as the experimental group, but will receive sham neurofeedback.

Who Is Running the Clinical Trial?

Trustees of Princeton University

Lead Sponsor

Trials

2

Recruited

1,700+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7871643/

Targeting hippocampal hyperactivity with real-time fMRI ... Results of this study will reveal whether real-time fMRI neurofeedback is able to reduce hippocampal hyperactivity and thereby improve memory performance.

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

a systematic review of real-time fMRI neurofeedback ... We found that rtfMRI-based NF training is efficient for modulating insula activity and its associated behavioral/symptom-related and neural changes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07122739

Study Details | NCT07122739 | Neurofeedback to Reduce ... Active neurofeedback will reinforce negative dlPFC-hippocampal functional connectivity, as this is expected to increase memory control ability. Intervention/ ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2213158220300280

Using connectivity-based real-time fMRI neurofeedback to ... The current study examined the potential of connectivity-based real-time functional magnetic imaging neurofeedback (rt-fMRI-nf) for enhancing DLPFC – ACC ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2019.00242/full

Emotion Regulation of Hippocampus Using Real-Time ... This study investigated the feasibility of NF training of healthy participants to self-regulate the activation of the hippocampus.

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

A systematic review of fMRI neurofeedback reporting and ... Out of 78% of studies reporting results, 60% (29/48) reported significant improvement of symptoms, 27% reported no difference, and the remaining 6 (13%) ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352154615000625

Cognitive enhancement through real-time fMRI ... Real-time fMRI enables neurofeedback of localized brain activity across the entire brain. · Self-regulation of localized and network activity can be learned.

8. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2020.00060/full

A Guide to Literature Informed Decisions in the Design of ... Rt-fMRI neurofeedback works by providing a representation of hemodynamic response in the brain compared to some baseline, allowing subjects to implicitly learn ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7856210/

A meta-analysis of brain and behavioral outcomes - PMC We present the first meta-analysis of rtfMRI-NF for psychiatric disorders, evaluating its impact on brain and behavioral outcomes.

10. mdpi.com mdpi.com/2076-3425/14/7/700

The Clinical Impact of Real-Time fMRI Neurofeedback on ... Successful modulation of brain activity was reported in between 25 and 50 percent of study samples, while neural effects in clinical samples were more diverse ...