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

NCT ID: NCT05933148

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-12
• Study Completion Date: 2027-04-30

Brief Summary

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.

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.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active Neurofeedback

Participants randomized to Active neurofeedback will receive real-time data depicting MOFC-precuneus brain activity while in the scanner.

Group Type: ACTIVE_COMPARATOR

Siemens 7T MRI

Intervention Type: DEVICE

The active neurofeedback session will be done within the 7T MRI.

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.

Group Type: SHAM_COMPARATOR

Sham Neurofeedback

Intervention Type: DEVICE

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.

Interventions

Siemens 7T MRI

The active neurofeedback session will be done within the 7T MRI.

Intervention Type: 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.

Intervention Type: DEVICE

Other Intervention Names

fMRI

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Yael Jacob

Assistant Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yael Jacob, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School Of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Grace S. Butler, BA

Role: CONTACT

grace.butler@mssm.edu

(212) 585-4623 ext. 54623

Rachel Krasner, BA

Role: CONTACT

rachel.krasner@mssm.edu

Facility Contacts

Grace S Butler, BA

Role: primary

grace.butler@mssm.edu

(212) 585-4623 ext. 54623

Rachel Krasner, BA

Role: backup

rachel.krasner@mssm.edu

Other Identifiers

STUDY-22-00048

Identifier Type: -

Identifier Source: org_study_id