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

Trial Summary

What is the purpose of this trial?

Post-traumatic stress disorder (PTSD) is a debilitating and highly prevalent psychiatric disorder that develops in the aftermath of trauma exposure (APA, 2013). PTSD has been strongly associated with altered activation patterns within several large-scale brain networks and, as such, it has been suggested that normalizing pathological brain activation may be an effective treatment approach. The objective of this proposed study is to investigate the ability of PTSD patients to self-regulate aberrant neural circuitry associated with PTSD psychopathology using real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback. Here, the investigators are building upon previous single-session pilot studies examining the regulation of the amygdala and the posterior cingulate cortex (PCC) in PTSD (Nicholson et al., 2021) (Nicholson et al., 2016) by: (1) Examining the effect of multiple sessions of rt-fMRI neurofeedback and, (2) Comparing PCC- and amygdala-targeted rt-fMRI neurofeedback to sham-control groups with regards to changes in PTSD symptoms and neural connectivity.

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 data supports the effectiveness of the treatment 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 symptom improvements. A study found that two out of three veterans with chronic PTSD experienced meaningful symptom reduction, suggesting this treatment could be promising for PTSD. ^{1 2 3 4 5}

Is fMRI neurofeedback safe for humans?

In a feasibility study with war veterans with PTSD, all participants tolerated the fMRI neurofeedback training well, suggesting it is generally safe for humans. ^{2 3 4 6 7}

How does fMRI Neurofeedback treatment differ from other PTSD treatments?

fMRI Neurofeedback is unique because it uses real-time brain imaging to help patients learn to control specific brain regions, like the amygdala, which is involved in emotional responses. This approach is different from traditional PTSD treatments as it provides immediate feedback on brain activity, allowing patients to develop personalized strategies for managing their symptoms. ^{1 2 3 4 8}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Data-Driven Approach to the Analysis of Real-Time FMRI Neurofeedback Data: Disorder-Specific Brain Synchrony in PTSD. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Time fMRI Neurofeedback with War Veterans with Chronic PTSD: A Feasibility Study. [2023]

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

Framework for Accurate Classification of Self-Reported Stress From Multisession Functional MRI Data of Veterans With Posttraumatic Stress. [2023]

4. United States 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Quantification of adverse events associated with functional MRI scanning and with real-time fMRI-based training. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Neurofeedback training for alcohol dependence versus treatment as usual: study protocol for a randomized controlled trial. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback training of the amygdala activity with simultaneous EEG in veterans with combat-related PTSD. [2021]