Neurofeedback Enhanced Cognitive Reappraisal Training - Phase 4

This study seeks to understand emotion regulation in those with young adults 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 hypotheses include:

• Participants receiving veritable-Neurofeedback (NF) will show a greater activation increases in the prefrontal cortex (PFC) compared to sham-NF
• Participants receiving veritable-NF will show greater cognitive reappraisal (CR) ability compared to those receiving sham-NF
• PFC activation will positively correlate with CR ability

Study Overview

• Status: Recruiting
• Conditions: Generalized Anxiety Disorder; Anxiety; Social Anxiety Disorder; Panic Disorder
• Intervention / Treatment: Other: Functional magnetic resonance imaging (fMRI) with Veritable-NF; Other: fMRI with Sham-NF

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Stchur, MSW; Phone Number: 734-936-1323; Email: lmarine@med.umich.edu
• Study Contact Backup: Name: Sophia Hovakimian; Phone Number: 734-232-0129; Email: shovakim@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Sophia Hovakimian; Phone Number: 734-232-0129; Email: shovakim@med.umich.edu
      • Principal Investigator: Stefanie Russman Block, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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
• Score of 2 or more on at least 1 question from GAD/CROSS-AD composite
• Medically and physically able to consent

• Not regularly taking any medication, prescription or non-prescription, with psychotropic effects other than:

  1. Buspirone, or antidepressant (e.g., selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)) with stable dosage for past 4 weeks
  2. The same oral hormonal contraceptive for at least 3 months
• 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, Posttraumatic Stress Disorder, or Bipolar Disorder
• Current substance abuse or dependence (past 6 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Veritable-NF	Other: Functional magnetic resonance imaging (fMRI) with Veritable-NF; Participants will complete 4 visits (some can be done virtually). The baseline visit will include a clinical interview. Eligible participants will complete a series of questionnaires and a practice session at visit 2, and may do a mock scan if the visit is in person. Visit 3 will take place within 5 days of the practice session. Participants will have an fMRI with real neurofeedback and answer a series of questions pertaining to the scan. 2 weeks after visit 3, participants will revisit the questionnaires they completed at baseline. Visit 4 will take place one month after visit 3 and will include a follow-up interview with an assessor and the final questionnaire collection.
Active Comparator: Sham-NF	Other: fMRI with Sham-NF; Participants will complete 4 visits (some can be done virtually). The baseline visit will include a clinical interview. Eligible participants will complete a series of questionnaires and a practice session at visit 2, and may do a mock scan if the visit is in person. Visit 3 will take place within 5 days of the practice session. Participants will have an fMRI with neurofeedback that looks similar to real neurofeedback but does not reflect their true brain signal. Afterwards, they will answer a series of questions pertaining to the scan. 2 weeks after visit 3, participants will revisit the questionnaires they completed at baseline. Visit 4 will take place one month after visit 3 and will include a follow-up interview with an assessor and the final questionnaire collection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in prefrontal cortex (PFC) activity (baseline to transfer run) from the reappraise > look contrast		Approximately 60 minutes
Change in negative affect ratings of images from the 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 from the IAPS 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in amygdala-PFC 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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Stefanie Russman Block, Ph.D, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: functional magnetic resonance imaging
• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Phobia, Social; Anxiety Disorders; Panic Disorder
• Other Study ID Numbers: HUM00209563 - phase 4; 1K23MH133063-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No