Neurofeedback Enhanced Cognitive Reappraisal Training

Study Overview
=================
Brief Summary
-----------------
This study seeks to understand emotion regulation in those with anxiety using real-time functional magnetic resonance imaging neurofeedback, a tool that allows individuals to control brain activity. The goal of this project is to understand how receiving feedback about one's own brain activity relates to emotion regulation ability. This work will help the study team understand the brain areas involved in emotion regulation and could lay the groundwork to test if psychotherapy outcomes can be enhanced using neurofeedback. The study hypothesis include: Participants receiving veritable-Neurofeedback (NF) will show a greater activation increase in the dorsomedial prefrontal cortex (dmPFC) compared to sham-NF Participants receiving veritable-NF will show greater cognitive reappraisal (CR) ability compared to those receiving sham-NF Prefrontal cortex activation will positively correlate with CR ability The veritable-NF group will report decreased symptom severity and increased CR use compared to the sham-NF group Increase in NF-induced brain activation will correlate with decreased symptom severity and increased CR use at follow-up

Official Title
-----------------
Neurofeedback Enhanced Cognitive Reappraisal Training

Conditions
-----------------
Anxiety, Social Anxiety Disorder, Panic Disorder, Generalized Anxiety Disorder

Intervention / Treatment
-----------------
* Device: Functional magnetic resonance imaging (fMRI) with Veritable-NF
* Device: fMRI with Sham-NF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Primary diagnosis (primary source of distress and/or interference) of generalized anxiety disorder, social anxiety disorder, panic disorder or illness anxiety disorder based on structured interview. Comorbid phobic disorders allowed, but these cannot be the primary source of interference or distress due to the lowered chances of encountering anxiety-provoking stimuli during the study period Medically and physically able to consent Not taking any medication, prescription or non-prescription with psychotropic effects other than birth control or antidepressant (i.e., selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) with stable dosage for past 4 week For females, not currently pregnant or actively trying to become pregnant Ability to tolerate small, enclosed spaces without anxiety No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition (per protocol) Size compatible with scanner gantry (per protocol) Exclusion Criteria: Current diagnosis of Obsessive Compulsive Disorder or Posttraumatic Stress Disorder Current course of individual or group psychotherapy Current substance abuse or dependence (past 12 months) Active suicidality with plan or intent Current psychosis History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure History of closed head injury, e.g., loss of consciousness greater (>) approximately ( ) 5 minutes, hospitalization, neurological sequela

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Veritable-NF<br> | Device: Functional magnetic resonance imaging (fMRI) with Veritable-NF<br>* Participants will have 4 visits (some can be done virtually). The baseline visit will include an interview and questionnaires. Eligible participants will have a practice session at visit 2, and may do a mock scanner if the visit is in person. Visit 3 will take place within 5 days of the practice session and participants will be asked to complete questionnaires and have an fMRI with the real neurofeedback. Visit 4 will take place one month after visit 3 and will include a follow-up interview with a trainer assessor as well as questionnaires. Additionally, 2 weeks after visit 3 participants will also complete some questionnaires online.<br>|
| Active Comparator: Sham-NF<br> | Device: fMRI with Sham-NF<br>* Participants will have 4 visits (some can be done virtually). The baseline visit will include an interview and questionnaires. Eligible participants will have a practice session at visit 2, and may do a mock scanner if the visit is in person. Visit 3 will take place within 5 days of the practice session and participants will be asked to complete questionnaires and have an fMRI with feedback that looks similar to real neurofeedback, but is computer generated. Visit 4 will take place 2 weeks after visit 3 and participants will complete more questionnaires.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in dorsomedial prefrontal cortex (dmPFC) activity (baseline to transfer run) from the reappraise > look contrast on the Emotion Regulation Task (ERT) |  | Approximately 60 minutes | 
| Change negative affect ratings of images from International Affective Picture System (IAPS) | The Self-Assessment Manikin (SAM) is a pictorial assessment technique in which a changing manikin figure depicts values along the primary dimension of affective valence (positive/negative). Users may indicate emotional reactions along a scale from 1-9, with higher numbers indicating greater negative affect. After the scan, participants will rate each image they saw along this scale. Differences in SAM ratings from look to reappraise trials will be evaluated and compared between sham-NF and veritable-NF groups. | Approximately 60 minutes | 
| Change in score on the Hamilton Anxiety Rating Scale (HAM-A) from initial assessment to one-month follow-up. | The 14-item Hamilton Anxiety Rating Scale (HAMA-14) is a clinician-rated assessment (structured interview) of patients' anxious symptoms. There is a possible score from 0-56 with a higher score meaning worse symptoms. | Baseline, 1 month | 
| Change in score on the reappraisal subscale of the Emotion Regulation Questionnaire (ERQ) for Cognitive Reappraisal from initial assessment to one-month follow-up. | This is a 10-item scale that participants will complete. Questions 1, 3, 5, 7, 8, 10 (strongly disagree (1) to strongly agree (7) will be scored for the Cognitive Reappraisal facet. Scores range from 6-42 with higher scores meaning greater cognitive reappraisal. | Baseline, 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in amygdala-dmPFC functional connectivity (baseline to transfer) from reappraise > look contrast | To examine amygdala connectivity, the study team will use a psychophysiological interaction analysis. Deconvolved time series from anatomical left and right amygdala seeds for each participant will be multiplied by a vector for the reappraise > look contrast at each run (baseline, Neruofeedback1 (NF1), NF2, NF3, transfer). Regressors for the seed time series, the original condition and the interaction term will be convolved with the canonical hemodynamic response function. Change in connectivity from pre-to-post training will be calculated by subtracting the baseline-run contrast map from the transfer-run contrast map. Resulting contrast maps will be entered into second-level random effects analyses. | Approximately 60 minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
functional magnetic resonance imaging