Network Neurofeedback Using 7-Tesla MRI to Reduce Rumination Levels in Depression

August 15, 2025 updated by: Yael Jacob, Icahn School of Medicine at Mount Sinai

Network-based Real-time Neurofeedback Using Ultra-high Field MRI to Reduce Rumination Levels in Depression

Patients with major depressive disorder (MDD) exhibit increased levels of rumination (i.e. repetitive thinking and focus on negative mood states) which have been found to increase the risk of depressive relapse. The ability to reduce rumination levels among these patients is greatly needed. Rumination is known to be associated with the default mode network (DMN) region activity. Implementing the Dependency Network Analysis (DEPNA), a recently developed method by the research team to quantify the connectivity influence of network nodes, found that rumination was significantly associated with lower connectivity influence of the left medial orbitofrontal cortex (MOFC) on the right precuneus, both key regions within the DMN. This study implements the first real-time fMRI neurofeedback (Rt-fMRI-NF) network-based protocol for up-regulation of the MOFC influence on the precuneus in patients with MDD to reduce rumination levels. This will allow for more accurate explicit brain connections modulation than the standard single brain region activity; creating a larger opportunity for target clinical neuromodulation treatment in individuals with MDD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Major depressive disorder (MDD) is the world's largest health problem, and current available treatments fail at relieving symptoms for many patients. Rumination, which is conceptualized as repetitive thinking and focus on one's distress and negative mood states is a core feature of MDD. Patients with MDD exhibit increased levels of rumination which have been found to increase the risk of depressive relapse in remitted patients. The ability to reduce rumination levels among these patients is greatly needed.

Neurofeedback (NF) is a technique that feeds back information about brain signals to the individual in real-time, to allow for implicit modulation of the brain signal in order to improve performance. Yet, classic real-time fMRI-NF protocols focus on single region activity neglecting to consider the neural network dynamics, accounting for direct influences between regions.

Implementing the Dependency Network Analysis (DEPNA), a method developed by the research team, tested whether network connectivity influences during resting-state functional MRI (fMRI) are associated with rumination in patients with MDD. The research team found that rumination was significantly associated with lower connectivity influence of the left medial orbito-frontal cortex (MOFC) on the right precuneus, both key regions within the DMN. This is in line with intracranial recordings studies showing that MOFC activity precedes the precuneus in response to emotional stimuli.

The research team intend to extend this work by conducting the first real-time fMRI neurofeedback (Rt-fMRINF) protocol for up-regulation of the MOFC influence on the precuneus in patients with MDD and healthy controls to reduce rumination levels. The research team aims to develop an advanced ultra-high field MRI protocol that will allow for rt-fMRI-NF derived from networks' connectivity features as constructed by the DEPNA, and thus training the subject to control explicit brain connections. Specifically, the research team aims to train MDD patients to better regulate rumination levels by upregulating the influence of the MOFC on the precuneus.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • New York
      • New York City, New York, United States, 10029
        • Recruiting
        • Icahn School Of Medicine At Mount Sinai
        • Contact:
        • Principal Investigator:
          • Yael Jacob
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Male or female aged 18-65 years who either meet DSM-5 Axis Disorders (SCID) or the Mini International Neuropsychiatric Interview (MINI) for major depressive disorder (MDD) with a current major depressive episode OR does not meet for any current or past psychiatric diagnoses
  • Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process

Exclusion Criteria:

  • Any current or history of schizophrenia or other psychotic disorder, neurodevelopmental disorder, or neurocognitive disorder for patients, active substance use disorder within the past 6 months
  • Unstable medical illness, concomitant use of any medication with central nervous system activity within 1 week of MRI scan
  • Pregnancy
  • Patients who are currently hospitalized in the inpatient psychiatric units at Mount Sinai Hospital or involuntarily admitted/court-ordered
  • Subjects judged to be at serious and imminent suicidal or homicidal risk by the study-affiliated psychiatrist or another MD, and contradictions to MRI

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active Neurofeedback
Participants randomized to Active neurofeedback will receive real-time data depicting MOFC-precuneus brain activity while in the scanner.
Device: Siemens 7T MRI
The active neurofeedback session will be done within the 7T MRI.
Other Names:
  • fMRI
Sham Comparator: Sham Neurofeedback
Participants randomized to the Sham neurofeedback control group will receive the feedback of a prior scanned participant's active MOFC-precuneus up-regulation and not their own brain activity. This condition will still visually resemble the active conditions.
Device: Sham Neurofeedback
The sham Neurofeedback resembles the active condition but participants will not see their own brain activity and will instead view a past participant's active feedback from their same population group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Self-reported rumination related to negative affect as measured by Rumination Response Style (RRS)
Time Frame: Pre-Neurofeedback (day 0) and Post-Neurofeedback (MRI assessment day 1)
The RRS measures ruminative responses to depressed mood. The content of the items is related to depressive cognitions and their possible causes and consequences. Total scores on the RSS can range from 22 to 88, with higher scores corresponding to higher levels of rumination.
Pre-Neurofeedback (day 0) and Post-Neurofeedback (MRI assessment day 1)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Self-reported rumination related to negative affect as measured by Rumination Response Style (RRS)
Time Frame: Pre-MRI Scan at screening (day 0)
The RRS measures ruminative responses to depressed mood. The content of the items is related to depressive cognitions and their possible causes and consequences. Total scores on the RSS can range from 22 to 88, with higher scores corresponding to higher levels of rumination.
Pre-MRI Scan at screening (day 0)
Self-reported rumination related to negative affect as measured by Rumination Response Style (RRS)
Time Frame: Post-MRI scan at follow up visit 24 hours
The RRS measures ruminative responses to depressed mood. The content of the items is related to depressive cognitions and their possible causes and consequences. Total scores on the RSS can range from 22 to 88, with higher scores corresponding to higher levels of rumination.
Post-MRI scan at follow up visit 24 hours
Self-reported rumination related to negative affect as measured by Rumination Response Style (RRS)
Time Frame: Post-MRI scan at follow up visit day 7
The RRS measures ruminative responses to depressed mood. The content of the items is related to depressive cognitions and their possible causes and consequences. Total scores on the RSS can range from 22 to 88, with higher scores corresponding to higher levels of rumination.
Post-MRI scan at follow up visit day 7
Self-reported rumination related to negative affect as measured by Rumination Response Style (RRS)
Time Frame: Post-MRI scan at follow up visit day 30
The RRS measures ruminative responses to depressed mood. The content of the items is related to depressive cognitions and their possible causes and consequences. Total scores on the RSS can range from 22 to 88, with higher scores corresponding to higher levels of rumination.
Post-MRI scan at follow up visit day 30
Self-reported rumination related to negative affect as measured by Perceive Stress Scale (PSS)
Time Frame: Pre-MRI Scan at screening (day 0)
A 10-item questionnaire, each item scored 0 (never) to 4 (very often), full scale from 0-40, with higher score indicating higher perceived stress
Pre-MRI Scan at screening (day 0)
Self-reported rumination related to negative affect as measured by Perceive Stress Scale (PSS)
Time Frame: Post-MRI scan at follow up visit 24 hours
A 10-item questionnaire, each item scored 0 (never) to 4 (very often), full scale from 0-40, with higher score indicating higher perceived stress
Post-MRI scan at follow up visit 24 hours
Self-reported rumination related to negative affect as measured by Perceive Stress Scale (PSS)
Time Frame: Post-MRI scan at follow up visit day 7
A 10-item questionnaire, each item scored 0 (never) to 4 (very often), full scale from 0-40, with higher score indicating higher perceived stress
Post-MRI scan at follow up visit day 7
Self-reported rumination related to negative affect as measured by Perceive Stress Scale (PSS)
Time Frame: Post-MRI scan at follow up visit day 30
A 10-item questionnaire, each item scored 0 (never) to 4 (very often), full scale from 0-40, with higher score indicating higher perceived stress
Post-MRI scan at follow up visit day 30
Self-reported rumination related to negative affect as measured by Quick Inventory of Depressive Symptomatology (QIDS)
Time Frame: Pre-MRI scan at screening (day 0)
Total QIDS scores range from 0 to 27 with scores of 5 or lower indicative of no depression, scores from 6 to 10 indicating mild depression, 11 to 15 indicating moderate depression, 16 to 20 reflecting severe depression, and total scores greater than 21 indicating very severe depression
Pre-MRI scan at screening (day 0)
Self-reported rumination related to negative affect as measured by Quick Inventory of Depressive Symptomatology (QIDS)
Time Frame: Post-MRI scan at follow up visit 24 hours
Total QIDS scores range from 0 to 27 with scores of 5 or lower indicative of no depression, scores from 6 to 10 indicating mild depression, 11 to 15 indicating moderate depression, 16 to 20 reflecting severe depression, and total scores greater than 21 indicating very severe depression
Post-MRI scan at follow up visit 24 hours
Self-reported rumination related to negative affect as measured by Quick Inventory of Depressive Symptomatology (QIDS)
Time Frame: Post-MRI scan at follow up visit day 7
Total QIDS scores range from 0 to 27 with scores of 5 or lower indicative of no depression, scores from 6 to 10 indicating mild depression, 11 to 15 indicating moderate depression, 16 to 20 reflecting severe depression, and total scores greater than 21 indicating very severe depression
Post-MRI scan at follow up visit day 7
Self-reported rumination related to negative affect as measured by Quick Inventory of Depressive Symptomatology (QIDS)
Time Frame: Post-MRI scan at follow up visit day 30
Total QIDS scores range from 0 to 27 with scores of 5 or lower indicative of no depression, scores from 6 to 10 indicating mild depression, 11 to 15 indicating moderate depression, 16 to 20 reflecting severe depression, and total scores greater than 21 indicating very severe depression
Post-MRI scan at follow up visit day 30
Self-reported rumination related to negative affect as measured by Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Pre-MRI scan at screening (day 0)
Each of the 10 items is rated on a scale of 0 to 6. These individual item scores are added together to form a total score, which can range between 0 and 60 points; higher scores indicated increased depression severity
Pre-MRI scan at screening (day 0)
Self-reported rumination related to negative affect as measured by Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Post-MRI scan at follow up visit 24 hours
Each of the 10 items is rated on a scale of 0 to 6. These individual item scores are added together to form a total score, which can range between 0 and 60 points; higher scores indicated increased depression severity
Post-MRI scan at follow up visit 24 hours
Self-reported rumination related to negative affect as measured by Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Post-MRI scan at follow up visit day 7
Each of the 10 items is rated on a scale of 0 to 6. These individual item scores are added together to form a total score, which can range between 0 and 60 points; higher scores indicated increased depression severity
Post-MRI scan at follow up visit day 7
Self-reported rumination related to negative affect as measured by Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Post-MRI scan at follow up visit day 30
Each of the 10 items is rated on a scale of 0 to 6. These individual item scores are added together to form a total score, which can range between 0 and 60 points; higher scores indicated increased depression severity
Post-MRI scan at follow up visit day 30

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Investigators

  • Principal Investigator: Yael Jacob, PhD, Icahn School Of Medicine At Mount Sinai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 12, 2023

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

June 21, 2023

First Submitted That Met QC Criteria

July 5, 2023

First Posted (Actual)

July 6, 2023

Study Record Updates

Last Update Posted (Actual)

August 17, 2025

Last Update Submitted That Met QC Criteria

August 15, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY-22-00048

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Not applicable to the aims of the study.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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