fMRI-Neurofeedback for PTSD

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Andrew Nicholson

Must not be taking: Opioids

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

No Placebo Group

Approved in 1 Jurisdiction

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.

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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.

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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.

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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

I am between 18 and 65 years old.

Exclusion Criteria

Meeting criteria for substance use disorder in the past three months

I am currently in therapy specifically for trauma.

History of claustrophobia

Trial 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)

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Lawson Health Research Institute London, Canada

Who Is Running the Clinical Trial?

Andrew Nicholson Lead Sponsor

McMaster University Collaborator

Western University Collaborator

University of Ottawa Collaborator

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] Brain-computer interfaces (BCIs) can be used in real-time fMRI neurofeedback (rtfMRI NF) investigations to provide feedback on brain activity to enable voluntary regulation of the blood-oxygen-level dependent (BOLD) signal from localized brain regions. However, the temporal pattern of successful self-regulation is dynamic and complex. In particular, the general linear model (GLM) assumes fixed temporal model functions and misses other dynamics. We propose a novel data-driven analyses approach for rtfMRI NF using intersubject covariance (ISC) analysis. The potential of ISC was examined in a reanalysis of data from 21 healthy individuals and nine patients with post-traumatic stress-disorder (PTSD) performing up-regulation of the anterior cingulate cortex (ACC). ISC in the PTSD group differed from healthy controls in a network including the right inferior frontal gyrus (IFG). In both cohorts, ISC decreased throughout the experiment indicating the development of individual regulation strategies. ISC analyses are a promising approach to reveal novel information on the mechanisms involved in voluntary self-regulation of brain signals and thus extend the results from GLM-based methods. ISC enables a novel set of research questions that can guide future neurofeedback and neuroimaging investigations.

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

Real-Time fMRI Neurofeedback with War Veterans with Chronic PTSD: A Feasibility Study. [2023] Many patients with post-traumatic stress disorder (PTSD), especially war veterans, do not respond to available treatments. Here, we describe a novel neurofeedback (NF) intervention using real-time functional magnetic resonance imaging for treating and studying PTSD. The intervention involves training participants to control amygdala activity after exposure to personalized trauma scripts. Three combat veterans with chronic PTSD participated in this feasibility study. All three participants tolerated well the NF training. Moreover, two participants, despite the chronicity of their symptoms, showed clinically meaningful improvements, while one participant showed a smaller symptom reduction. Examination of changes in resting-state functional connectivity patterns revealed a normalization of brain connectivity consistent with clinical improvement. These preliminary results support feasibility of this novel intervention for PTSD and indicate that larger, well-controlled studies of efficacy are warranted.

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] Background: Posttraumatic stress disorder (PTSD) is a significant burden among combat Veterans returning from the wars in Iraq and Afghanistan. While empirically supported treatments have demonstrated reductions in PTSD symptomatology, there remains a need to improve treatment effectiveness. Functional magnetic resonance imaging (fMRI) neurofeedback has emerged as a possible treatment to ameliorate PTSD symptom severity. Virtual reality (VR) approaches have also shown promise in increasing treatment compliance and outcomes. To facilitate fMRI neurofeedback-associated therapies, it would be advantageous to accurately classify internal brain stress levels while Veterans are exposed to trauma-associated VR imagery. Methods: Across 2 sessions, we used fMRI to collect neural responses to trauma-associated VR-like stimuli among male combat Veterans with PTSD symptoms (N = 8). Veterans reported their self-perceived stress level on a scale from 1 to 8 every 15 s throughout the fMRI sessions. In our proposed framework, we precisely sample the fMRI data on cortical gray matter, blurring the data along the gray-matter manifold to reduce noise and dimensionality while preserving maximum neural information. Then, we independently applied 3 machine learning (ML) algorithms to this fMRI data collected across 2 sessions, separately for each Veteran, to build individualized ML models that predicted their internal brain states (self-reported stress responses). Results: We accurately classified the 8-class self-reported stress responses with a mean (± standard error) root mean square error of 0.6 (± 0.1) across all Veterans using the best ML approach. Conclusions: The findings demonstrate the predictive ability of ML algorithms applied to whole-brain cortical fMRI data collected during individual Veteran sessions. The framework we have developed to preprocess whole-brain cortical fMRI data and train ML models across sessions would provide a valuable tool to enable individualized real-time fMRI neurofeedback during VR-like exposure therapy for PTSD.

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] Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) has gained popularity as an experimental treatment for a variety of psychiatric illnesses. However, there has yet to be a quantitative review regarding its efficacy. Here, we present the first meta-analysis of rtfMRI-NF for psychiatric disorders, evaluating its impact on brain and behavioral outcomes. Our literature review identified 17 studies and 105 effect sizes across brain and behavioral outcomes. We find that rtfMRI-NF produces a medium-sized effect on neural activity during training (g = .59, 95 % CI [.44, .75], p

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

Making sense of real-time functional magnetic resonance imaging (rtfMRI) and rtfMRI neurofeedback. [2018] This review explains the mechanism of functional magnetic resonance imaging in general and specifically introduces real-time functional magnetic resonance imaging as a method for training self-regulation of brain activity. Using real-time functional magnetic resonance imaging neurofeedback, participants can acquire control over their own brain activity. In patients with neuropsychiatric disorders, this control can potentially have therapeutic implications. In this review, the technical requirements are presented and potential applications and limitations are discussed.

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

Quantification of adverse events associated with functional MRI scanning and with real-time fMRI-based training. [2021] Although functional magnetic resonance imaging (fMRI) is in widespread research use, the safety of this approach has not been extensively quantitatively evaluated. Real-time fMRI (rtfMRI)-based training paradigms use fMRI neurofeedback and cognitive strategies to alter regional brain activation, and are currently being evaluated as a novel approach to treat neurological and psychiatric conditions.

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

Neurofeedback training for alcohol dependence versus treatment as usual: study protocol for a randomized controlled trial. [2022] Real-time functional magnetic resonance imaging (rtfMRI) is used for neurofeedback training (NFT). Preliminary results suggest that it can help patients to control their symptoms. This study uses rtfMRI NFT for relapse prevention in alcohol dependence.

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] Posttraumatic stress disorder (PTSD) is a chronic and disabling neuropsychiatric disorder characterized by insufficient top-down modulation of the amygdala activity by the prefrontal cortex. Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging method with potential for modifying the amygdala-prefrontal interactions. We report the first controlled emotion self-regulation study in veterans with combat-related PTSD utilizing rtfMRI-nf of the amygdala activity. PTSD patients in the experimental group (EG, n = 20) learned to upregulate blood‑oxygenation-level-dependent (BOLD) activity of the left amygdala (LA) using the rtfMRI-nf during a happy emotion induction task. PTSD patients in the control group (CG, n = 11) were provided with a sham rtfMRI-nf. The study included three rtfMRI-nf training sessions, and EEG recordings were performed simultaneously with fMRI. PTSD severity was assessed before and after the training using the Clinician-Administered PTSD Scale (CAPS). The EG participants who completed the study showed a significant reduction in total CAPS ratings, including significant reductions in avoidance and hyperarousal symptoms. They also exhibited a significant reduction in comorbid depression severity. Overall, 80% of the EG participants demonstrated clinically meaningful reductions in CAPS ratings, compared to 38% in the CG. No significant difference in the CAPS rating changes was observed between the groups. During the first rtfMRI-nf session, functional connectivity of the LA with the orbitofrontal cortex (OFC) and the dorsolateral prefrontal cortex (DLPFC) was progressively enhanced, and this enhancement significantly and positively correlated with the initial CAPS ratings. Left-lateralized enhancement in upper alpha EEG coherence also exhibited a significant positive correlation with the initial CAPS. Reduction in PTSD severity between the first and last rtfMRI-nf sessions significantly correlated with enhancement in functional connectivity between the LA and the left DLPFC. Our results demonstrate that the rtfMRI-nf of the amygdala activity has the potential to correct the amygdala-prefrontal functional connectivity deficiencies specific to PTSD.