Multi-session fMRI-Neurofeedback in PTSD

NCT05456958 | Recruiting

• 1 other identifier: ANicho01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Post Traumatic Stress Disorder

Keywords

Real-time neurofeedback; Functional magnetic resonance imaging (fMRI); Post-traumatic stress disorder (PTSD); Posterior cingulate cortex (PCC); Amygdala

Outcome Measures

Primary Outcomes (2)

• Changes in PTSD symptoms over neurofeedback training sessions

  The change in PTSD symptoms, as measured by PTSD Checklist 5 (PCL-5) scores, will be assessed over the course of 3 neurofeedback training sessions and at a 1-month follow-up. PCL-5 is a self-report measure used to gauge the DSM-5 symptoms of PTSD. PCL-5 scores range from 0 to 80 with higher scores indicating more severe PTSD symptoms.

  Change in baseline (pre-neurofeedback) at 1-week intervals (i.e., post-neurofeedback session 1, 2, 3) and at a 1-month follow-up)

• Region-of-interest (ROI) downregulation analysis over neurofeedback training sessions

  In order to evaluate ROI downregulation (i.e., neurofeedback success), we will extract the event-related BOLD signal from the ROI during the regulate and view conditions.

  Change in ROI activation between neurofeedback sessions 1, 2, and 3

Secondary Outcomes (9)

• Change in depressive symptoms (i.e., BDI-II) over neurofeedback training sessions

  Change in baseline (pre-neurofeedback) at 1-week intervals (i.e., post-neurofeedback session 1, 2, 3) and at a 1-month follow-up)

• Change in emotion regulation abilities (i.e., DERS) over neurofeedback training sessions

  Change in baseline (pre-neurofeedback) at 1-week intervals (i.e., post-neurofeedback session 1, 2, 3) and at a 1-month follow-up)

• Change in trauma-related memory recall (i.e., RSDI) over neurofeedback training sessions

  Change in baseline (pre-neurofeedback) at 1-week intervals (i.e., post-neurofeedback session 1, 2, 3) and at a 1-month follow-up)

• Change in dissociation symptoms (i.e., MDI) over neurofeedback training sessions

  Change in baseline (pre-neurofeedback) at 1-week intervals (i.e., post-neurofeedback session 1, 2, 3) and at a 1-month follow-up)

• Change in emotional states of depression, anxiety, and stress (i.e., DASS-21) over neurofeedback training sessions

  Change in baseline (pre-neurofeedback) at 1-week intervals (i.e., post-neurofeedback session 1, 2, 3) and at a 1-month follow-up)

Study Arms (3)

Amygdala

EXPERIMENTAL

PTSD participants will receive a neurofeedback signal reflecting amygdala activity.

Other: MRI Biofeedback

Posterior cingulate cortex (PCC)

EXPERIMENTAL

PTSD participants will receive a neurofeedback signal reflecting PCC activity.

Other: MRI Biofeedback

Sham-control

EXPERIMENTAL

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

Other: Sham-MRI Biofeedback

Interventions

MRI Biofeedback OTHER

We will use state-of-the-art fMRI and neurofeedback of brain signals in order to teach patients with PTSD to self-regulate pathological brain activity that is associated with their symptoms. Indeed, feedback information is crucial for learning, where rt-fMRI-based neurofeedback makes information about brain activity accessible to our consciousness (Ros et al., 2014; Sitaram et al., 2017). It thus provides a reinforcement signal to induce personalized learning mechanisms, allowing individuals to search for appropriate cognitive strategies to voluntarily control brain activity. The feedback signal will come from activity within either the amygdala or PCC.

Amygdala; Posterior cingulate cortex (PCC)

Sham-MRI Biofeedback OTHER

In the sham-control arm (N=20), individuals will receive fake neurofeedback signal, i.e., from a successful participant in one of the experimental arms.

Sham-control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Participants will be asked for both their biological sex and gender-identity on a demographic form at the start of the study.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Fluent English speaker
• Comfortable using electronic devices (i.e., laptop, tablet, smartphone, etc.)
• Meet criteria for a primary diagnosis of PTSD via the DSM-5 on the Clinician Administered PTSD Scale (CAPS-5). Note: given high rates of PTSD co-morbidity with major depressive disorder and anxiety disorders, these participants will not be excluded from the study, allowing for a naturalistic sample
• Able to provide written informed consent.

You may not qualify if:

• Medical
• Pregnant women or women who are breastfeeding
• Serious illness (including cardiac, hepatic, renal, respiratory, endocrinologic, neurologic, or hematologic disease) that is not stabilized based on the judgment of primary investigator
• Contraindications for research MRI, including metallic implants
• Neurological disease, past head injury with loss of consciousness, stroke, seizures
• Major untreated medical illness (e.g., cancer, thyroid disorder)
• Any other condition that might interfere with the person's capacity to give informed consent, or to adhere to the study protocol.
• Psychological/Psychiatric
• Active substance use or abuse as defined by the MINI or judged to be a problem by the PI
• Current or past pain disorders, bipolar disorders or psychosis, schizophrenia, and any other psychotic disorder will be excluded
• Participants will also be excluded for active suicidality, history of pervasive developmental disorders, or any other major medical illnesses
• Meeting criteria for substance use disorder in the past three months on the MINI
• Chronic opioid analgesic use within the last three months
• Any other condition that might interfere with the person's capacity to give informed consent, or to adhere to the study protocol
• Current engagement in a primary trauma-focused psychotherapy treatment.

Sponsors & Collaborators

• Andrew Nicholson: lead
• McMaster University: collaborator
• University of Ottawa: collaborator
• Western University: collaborator

Study Sites (1)

Lawson Health Research Institute

London, Ontario, N6C 2R5, Canada

RECRUITING

Related Publications (18)

• Nicholson AA, Rabellino D, Densmore M, Frewen PA, Steryl D, Scharnowski F, Theberge J, Neufeld RWJ, Schmahl C, Jetly R, Lanius RA. Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real-time fMRI neurofeedback. Brain Behav. 2022 Jan;12(1):e2441. doi: 10.1002/brb3.2441. Epub 2021 Dec 18.

  PMID: 34921746 BACKGROUND

• Nicholson AA, Rabellino D, Densmore M, Frewen PA, Paret C, Kluetsch R, Schmahl C, Theberge J, Neufeld RW, McKinnon MC, Reiss J, Jetly R, Lanius RA. The neurobiology of emotion regulation in posttraumatic stress disorder: Amygdala downregulation via real-time fMRI neurofeedback. Hum Brain Mapp. 2017 Jan;38(1):541-560. doi: 10.1002/hbm.23402. Epub 2016 Sep 20.

  PMID: 27647695 BACKGROUND

• Weathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, Keane TM, Marx BP. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans. Psychol Assess. 2018 Mar;30(3):383-395. doi: 10.1037/pas0000486. Epub 2017 May 11.

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• Weathers, F. W., Litz, B. T., Keane, T. M., Palmieri, P. A., Marx, B. P., & Schnurr, P. P. (2013). The ptsd checklist for dsm-5 (pcl-5). Scale available from the National Center for PTSD at www. ptsd. va. gov, 10(4), 206.

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• Perasso, Giulia & Velotti, Patrizia. (2017). Difficulties in Emotion Regulation Scale. 10.1007/978-3-319-28099-8_810-1.

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• Briere J, Weathers FW, Runtz M. Is dissociation a multidimensional construct? Data from the Multiscale Dissociation Inventory. J Trauma Stress. 2005 Jun;18(3):221-31. doi: 10.1002/jts.20024.

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• Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress. 2015 Dec;28(6):489-98. doi: 10.1002/jts.22059. Epub 2015 Nov 25.

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• Hopper, J. W., Frewen, P. A., Sack, M., Lanius, R. A., & van der Kolk, B. A. (2007). The responses to Script-Driven Imagery Scale (RSDI): Assessment of state posttraumatic symptoms for psychobiological and treatment research. Journal of Psychopathology and Behavioral Assessment, 29(4), 249-268. https://doi.org/10.1007/s10862-007-9046-0

  BACKGROUND

• American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596

  BACKGROUND

• Ros T, J Baars B, Lanius RA, Vuilleumier P. Tuning pathological brain oscillations with neurofeedback: a systems neuroscience framework. Front Hum Neurosci. 2014 Dec 18;8:1008. doi: 10.3389/fnhum.2014.01008. eCollection 2014.

  PMID: 25566028 BACKGROUND

• Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, Weiskopf N, Blefari ML, Rana M, Oblak E, Birbaumer N, Sulzer J. Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2017 Feb;18(2):86-100. doi: 10.1038/nrn.2016.164. Epub 2016 Dec 22.

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  PMID: 21532953 BACKGROUND

• Lieberman JM, Lanius RA, Theberge J, Frey BN, Frewen PA, Scharnowski F, Steyrl D, Ros T, Densmore M, Tassinari E, Matic V, Hosseini-Kamkar N, Narikuzhy S, Hosseiny F, Jetly R, Nicholson AA. Study protocol for a multi-session randomized sham-controlled trial of PCC- and amygdala-targeted neurofeedback for the treatment of PTSD. BMC Psychiatry. 2025 Jul 15;25(1):698. doi: 10.1186/s12888-025-07050-5.

  PMID: 40665286 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Central Study Contacts

Andrew A Nicholson, PhD

CONTACT

437-349-9324; dr.andrewnicholson@gmail.com

Jonathan M Lieberman, BSc

CONTACT

647-501-0510; liebermj@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both investigators and participants will be blinded with regards to arm assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Adjunct Professor

Model Details: PTSD participants (N=60) will be randomly assigned to receive neurofeedback targeting one of two regions-of-interest - amygdala (N=20) or PCC (N=20) - or to the sham-control arm (N=20), where individuals will receive a fake neurofeedback signal (i.e., from a successful participant in one of the experimental arms, thereby controlling for motivational effects).

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 13, 2022
• Study Start: May 1, 2023
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)