fMRI-Neurofeedback for PTSD

Overseen By Jonathan M Lieberman, BSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Andrew Nicholson

Must not be taking: Opioids

Disqualifiers: Substance use, Bipolar, Psychosis, Claustrophobia, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help people with PTSD, a condition that can develop after experiencing trauma, learn to control specific brain activities contributing to their symptoms. Participants will use real-time MRI biofeedback, a technique providing feedback on brain activity, to regulate brain areas like the amygdala and the posterior cingulate cortex, which are linked to PTSD. The study will compare the effects of this neurofeedback with sham feedback to determine its effectiveness in reducing PTSD symptoms. Individuals diagnosed with PTSD and comfortable using electronic devices might be a good fit for this trial. As an unphased trial, this study offers participants the chance to contribute to innovative research that could lead to new PTSD treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are using chronic opioid analgesics or have active substance use issues, you may be excluded from participating.

What prior data suggests that this fMRI neurofeedback technique is safe for PTSD patients?

Research has shown that fMRI neurofeedback is generally well-tolerated by people with PTSD. Participants in studies learned to control their brain activity through real-time feedback without major side effects. No one in these studies reported serious negative effects from the treatment, suggesting it is safe for use.

The treatment uses MRI technology to provide live feedback on brain activity, helping patients learn to change how their brains respond to stress. Although researchers are still studying the treatment, earlier studies have found no major safety issues. This is encouraging for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using MRI neurofeedback for PTSD because it offers a unique, non-invasive way to directly influence brain activity. Unlike traditional treatments like therapy or medication, which often take time to show effects, MRI neurofeedback allows participants to receive real-time feedback on their brain activity, potentially leading to faster changes in brain patterns associated with PTSD. Specifically, this approach targets brain regions like the amygdala and the posterior cingulate cortex, which are crucial in processing emotions and self-reflection, respectively. By directly interacting with these brain areas, MRI neurofeedback could offer a new avenue for managing PTSD symptoms more effectively.

What evidence suggests that fMRI Neurofeedback might be an effective treatment for PTSD?

Research has shown that neurofeedback, a therapy where individuals learn to control their brain activity, can help reduce PTSD symptoms. Studies have found that this treatment offers moderate benefits for PTSD and can also improve related depression and anxiety. In this trial, participants will receive real-time fMRI neurofeedback, which uses brain scans to provide feedback, focusing on areas of the brain important for emotion and memory, such as the amygdala and the posterior cingulate cortex (PCC). Some participants will receive a sham neurofeedback signal as a control. Multiple studies support that this approach can lead to meaningful improvements, especially over time. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-65 with PTSD, comfortable with tech like laptops and smartphones. Participants must have a PTSD diagnosis as per DSM-5 criteria but can also have depression or anxiety disorders. Exclusions include pregnancy, serious illnesses, MRI contraindications (like metal implants), neurological issues, untreated major illnesses, substance abuse in the last three months, claustrophobia, prior neurofeedback therapy or brain stimulation treatments.

Inclusion Criteria

Fluent English speaker

Able to provide written informed consent

Comfortable using electronic devices (i.e., laptop, tablet, smartphone, etc.)

Exclusion Criteria

Meeting criteria for substance use disorder in the past three months

I am currently in therapy specifically for trauma.

History of claustrophobia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Clinical Assessment

Baseline clinical assessments including MINI and CAPS-5 to establish mental health disorder diagnoses and PTSD symptom severity

1 week

1 visit (in-person)

Self-report Assessments

Participants complete a battery of self-report questionnaires via REDCap

1 week

rt-fMRI Neurofeedback Sessions

3 rt-fMRI neurofeedback sessions over 3 weeks, including pre-session RSDI, localization scan, anatomical scan, resting-state scan, and task runs

3 weeks

3 visits (in-person)

Actigraphy Monitoring

Participants wear actigraphy devices to monitor biological rhythms and physical activity

7 weeks

Follow-up

Participants are monitored for changes in PTSD symptoms, interoceptive awareness, emotion regulation, and other measures at a 1-month follow-up

4 weeks

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• MRI Biofeedback
• Sham-MRI Biofeedback

Trial Overview The study tests if multiple sessions of real-time fMRI neurofeedback can help PTSD patients control abnormal brain activity linked to their condition. It compares two targets for feedback: the amygdala and posterior cingulate cortex against sham controls to see which affects symptoms and neural connectivity better.

How Is the Trial Designed?

Group I: Sham-control Experimental Treatment 1 Intervention

PTSD participants will receive a sham neurofeedback signal, i.e., from a successful participant in one of the experimental arms.

Group II: Posterior cingulate cortex (PCC) Experimental Treatment 1 Intervention

PTSD participants will receive a neurofeedback signal reflecting PCC activity.

Group III: Amygdala Experimental Treatment 1 Intervention

PTSD participants will receive a neurofeedback signal reflecting amygdala activity.

MRI Biofeedback is already approved in United States for the following indications:

Approved in United States as fMRI Neurofeedback for:

• Post-traumatic Stress Disorder (PTSD)

Who Is Running the Clinical Trial?

Andrew Nicholson

Lead Sponsor

Trials

1

Recruited

60+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Western University

Collaborator

Trials

31

Recruited

129,000+

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

Published Research Related to This Trial

This study investigates the use of real-time functional magnetic resonance imaging (rtfMRI) neurofeedback training (NFT) in alcohol-dependent patients to help them manage cravings and prevent relapse, with participants receiving six NFT sessions over four months.

The primary goal is to determine if NFT can effectively teach participants to regulate their brain responses to alcohol-related stimuli, potentially leading to reduced alcohol consumption, as measured by various metrics such as days abstinent and drinking frequency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback training for alcohol dependence versus treatment as usual: study protocol for a randomized controlled trial. Cox, WM., Subramanian, L., Linden, DE., et al.[2022]

Real-time functional magnetic resonance imaging (fMRI) allows individuals to gain control over their own brain activity through neurofeedback, which could be beneficial for self-regulation.

This technique has potential therapeutic implications for patients with neuropsychiatric disorders, although the review also discusses the technical requirements and limitations of its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Making sense of real-time functional magnetic resonance imaging (rtfMRI) and rtfMRI neurofeedback. Brühl, AB.[2018]

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]

In a study involving 114 chronic pain patients and 641 functional imaging scans, there were no significant increases in reported adverse events during fMRI or real-time fMRI (rtfMRI) training sessions compared to baseline sessions, indicating a strong safety profile for these procedures.

Over 90% of rtfMRI training sessions reported no adverse events, and when events did occur, they were mostly mild or moderate, suggesting that rtfMRI training is a safe approach for altering brain activation without increasing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantification of adverse events associated with functional MRI scanning and with real-time fMRI-based training. Hawkinson, JE., Ross, AJ., Parthasarathy, S., et al.[2021]

A novel neurofeedback intervention using real-time fMRI was tested on three combat veterans with chronic PTSD, and all participants tolerated the training well.

Two out of three participants experienced clinically meaningful improvements in their PTSD symptoms, along with changes in brain connectivity that aligned with these improvements, suggesting the potential efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time fMRI Neurofeedback with War Veterans with Chronic PTSD: A Feasibility Study. Gerin, MI., Fichtenholtz, H., Roy, A., et al.[2023]

A study involving 8 male combat Veterans with PTSD demonstrated that machine learning algorithms can accurately predict self-reported stress levels based on fMRI data collected during exposure to trauma-related virtual reality stimuli.

The developed framework for processing fMRI data could enhance real-time neurofeedback during virtual reality therapy, potentially improving treatment outcomes for Veterans with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Framework for Accurate Classification of Self-Reported Stress From Multisession Functional MRI Data of Veterans With Posttraumatic Stress. Goel, R., Tse, T., Smith, LJ., et al.[2023]

In a study involving 20 veterans with combat-related PTSD, real-time fMRI neurofeedback (rtfMRI-nf) allowed participants to upregulate activity in the left amygdala, leading to significant reductions in PTSD symptoms, particularly avoidance and hyperarousal.

80% of participants in the experimental group experienced clinically meaningful reductions in PTSD severity, indicating that rtfMRI-nf may effectively enhance amygdala-prefrontal connectivity and improve emotional regulation in PTSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback training of the amygdala activity with simultaneous EEG in veterans with combat-related PTSD. Zotev, V., Phillips, R., Misaki, M., et al.[2021]

A new data-driven analysis method called intersubject covariance (ISC) was tested on data from 21 healthy individuals and 9 PTSD patients, revealing differences in brain activity regulation, particularly in the anterior cingulate cortex (ACC) and right inferior frontal gyrus (IFG).

ISC analysis showed that both groups developed individual strategies for self-regulating brain activity over time, suggesting that this method can provide deeper insights into the mechanisms of brain signal regulation compared to traditional general linear model (GLM) approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Data-Driven Approach to the Analysis of Real-Time FMRI Neurofeedback Data: Disorder-Specific Brain Synchrony in PTSD. Zweerings, J., Sarasjärvi, K., Mathiak, KA., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10515677/

Neurofeedback for post-traumatic stress disorder: systematic ... Neurofeedback (NFB) was found to have moderate beneficial effects on PTSD symptoms, and positive effects on secondary outcomes such as depression and anxiety, ...

2. 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.

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1323485/full

Systematic review and meta-analysis of neurofeedback ... Based on newer published studies and the outcomes measured, NF has demonstrated a clinically meaningful effect size, with an increased effect size at follow-up.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03574974

Neurofeedback of Amygdala Activity for Post-traumatic ... The primary purpose of this study is to investigate the efficacy of neurofeedback (NF) of real-time functional magnetic resonance imaging (rt-fMRI) data of the ...

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6650780/

Current Status of Neurofeedback for Post-traumatic Stress ... With neurofeedback, patients can unconsciously self-regulate brain activity via real-time monitoring and feedback of the EEG or fMRI signals.

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2016.00111/epub

Real-Time fMRI Neurofeedback with PTSD Here, we describe a novel neurofeedback (NF) intervention using real-time functional magnetic resonance imaging for treating and studying PTSD. The ...

8. withpower.com withpower.com/trial/phase-post-traumatic-stress-disorder-ptsd-8-2022-94b17

fMRI-Neurofeedback for PTSD Research shows that real-time fMRI neurofeedback can help people with PTSD, like war veterans, learn to control brain activity related to stress, leading to ...