Neurofeedback to Treat Depression - 2

Reducing Neural Perseveration Through Closed Loop Real Time fMRI Neurofeedback to Alleviate Depressive Symptoms

This study tests the efficacy of a new psychotherapeutic strategy for reducing negative attention bias (and therefore depression severity) in participants with MDD. This real-time fMRI neurofeedback therapy uses cloud-based pattern classification to decode a patient's attentional state and dynamically modulate task stimuli (in a closed loop) based on this state.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Behavioral: Active Closed Loop Real Time fMRI Neurofeedback; Behavioral: Sham Closed Loop Real Time fMRI Neurofeedback

Detailed Description

The investigators will compare cloud based real time fMRI feedback with placebo (sham feedback) in reducing negative attention bias and depressive symptoms. This study will be the first dose-finding test of real-time fMRI effect on negative attention bias. Measures include: Structured Clinical Interview for DSM-5 (SCID), Clinician-administered diagnostic exam, Montgomery Asberg Depression Rating Scale (MADRS), Clinician-administered scale used to assess the severity of depression, State-Trait Anxiety Inventory (STAI), Self-report questionnaire used to measure types of anxiety and mood symptoms, Mood and Anxiety Symptom Questionnaire (MASQ), Negative perseveration during a go/no-go task, Go/no-go task with overlaid face/scene stimuli; brain response triggers next stimulus, Negative gaze, Negative gaze collected in gaze data following each real time fMRI feedback session

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yvette Sheline, M.D.; Phone Number: (215) 746-2637; Email: cndslab@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Center for Neuromodulation in Depression and Stress
      • Principal Investigator: Yvette Sheline, MD
      • Contact: Maria Prociuk; Phone Number: (215) 573-4229; Email: lmari@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Gender, inclusive
• Adult aged 18 - 65
• Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for MDD according to the Clinician-Administered MDD Scale for DSM-5 (unipolar depression or bipolar II depressed)
• Scores at least a minimum score of 16 on Montgomery Asberg Depression Rating Scale (MADRS)
• Normal cognition
• Participants must be able to read and understand English
• Participants must be able to provide consent

Exclusion Criteria:

• Pregnancy (female participants)
• Outside age range
• MRI contraindications (medical implant, claustrophobia, etc.)
• Use of psychoactive medication (including antidepressants) or currently in therapy
• Neurological disorder or any condition that in the view of the PI could impact brain data, cause depression, require medication that could cause depressive symptoms, or otherwise result in participant being unfit for study (for example, co-morbid psychotic, neurological disorders, developmentally or cognitively disabled/impaired, active alcohol or drug abuse/dependence within the past 6 months).
• Non-English speaking
• Non-correctable vision loss
• Refusal to provide informed consent
• representing an active suicide risk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Comparator: Active Neurofeedback; R33 Phase: Three training sessions. Each training session contains 32 minutes of active neurofeedback runs.	Behavioral: Active Closed Loop Real Time fMRI Neurofeedback; Active neurofeedback to target neural mechanisms underlying attentional bias in participants with major depressive discover (MDD)
Sham Comparator: Sham Comparator: Sham Neurofeedback; R33 Phase: Three training sessions. Each training session contains 32 minutes of sham (placebo) neurofeedback runs.	Behavioral: Sham Closed Loop Real Time fMRI Neurofeedback; Sham (placebo) neurofeedback to target neural mechanisms underlying attentional bias in participants with major depressive discover (MDD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Depression Rating Scale (MADRS)	Clinician administered scale to assess the severity of depression. MADRS scores will be compare the effect of real-time neurofeedback vs sham neurofeedback on depression outcome in patients with MDD. A MADRS score of 16 or higher is needed in order to be eligible to be enrolled in the study. The higher the MADRS score, the more depressed the individual will be. A lower MADRS score indicates that the individual's depressive symptoms have improved. A higher MADRS score indicates that the individual's depressive symptoms have worsened.	3 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Yvette Sheline, M.D., Center for Neuromodulation in Depression and Stress, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2025
• Primary Completion (Estimated): November 21, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 3, 2025
• First Submitted That Met QC Criteria: September 3, 2025
• First Posted (Estimated): September 8, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 849298-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will only be shared amongst the study sites.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No