Mindfulness-Based fMRI Neurofeedback for Depression (mbNF)

Targeting Adolescent Depression Symptoms Using Network-based Real-time fMRI Neurofeedback and Mindfulness Meditation (NIMH); Mindfulness-Based Real-Time fMRI Neurofeedback for Depression (IRB)

In the United States, adolescents experience alarmingly high rates of major depression, and gold-standard treatments are only effective for approximately half of patients. Rumination may be a promising treatment target, as it is well-characterized at the neural level and contributes to depression onset, maintenance, and recurrence as well as predicts treatment non-response. Accordingly, the proposed research will investigate whether an innovative mindfulness-based real-time functional magnetic resonance imaging (fMRI) neurofeedback intervention successfully elicits change in the brain circuit underlying rumination to improve clinical outcomes among depressed adolescents.

Study Overview

• Status: Recruiting
• Conditions: Rumination; Depression in Adolescence
• Intervention / Treatment: Other: Mindfulness + fMRI Neurofeedback

Detailed Description

Adolescent major depressive disorder (MDD) is common and debilitating. Presently, gold-standard treatments are only effective for approximately half of patients, underscoring the need to develop novel interventions, particularly to target core underlying mechanisms and more effectively treat this recurrent disorder.

Rumination, the tendency to perseverate about depressive symptoms, contributes to MDD onset and predicts treatment non-response and relapse. At the neural level, rumination is characterized by elevated functional connectivity within the default mode network (DMN), and similarly, prior research has consistently demonstrated patterns of DMN hyper-connectivity in MDD. Interestingly, mindfulness meditation, which trains attentional focus to the present moment, reduces perseverative thinking, ruminative tendencies, and depression symptoms. Further, prior research have shown that adolescents can apply mindfulness practices to decrease perceived stress, increase sustained attention, and suppress DMN activity. Although mindfulness has profound mental health benefits, for some, mindfulness alone may not be sufficient to mitigate ruminative tendencies during a depressive episode. That is, MDD symptoms, including reduced motivation, inattention, and lack of self-efficacy, may impede a patient's progress in successfully acquiring and utilizing mindfulness strategies necessary to change perceptions about one's environment and relationships. To directly address this challenge, this project will use real-time fMRI neurofeedback to enhance the acquisition and utilization of mindfulness skills to better target DMN hyper-connectivity, rumination, and depressive symptoms.

Specifically, a novel, mindfulness-based, real-time neurofeedback (mbNF) paradigm will be used whereby people observe a visual display of their brain activity and practice mindfulness to volitionally reduce DMN activation. Adolescents (N=90; ages 13-18 years) diagnosed with MDD will complete a ~45-minute mindfulness training outside the MRI scanner. To test target engagement of reducing DMN hyper-connectivity and dosing effects, adolescents will all receive mbNF and changes in brain connectivity will be examined (primary outcome). To examine dosing effects, adolescents will be randomized to receive either a 15- or a 30-minute mbNF session (n=45/dose group). Clinician-administered instruments, self-reports, and smartphone ecological momentary assessment will be used test whether mbNF contributes to a greater reduction in clinician assessed depression symptoms as well as decreased rumination post-treatment (secondary outcomes). As a whole, mbNF is directly in line with precision medicine initiatives, and if successful, could revolutionize clinical care for depressed adolescents.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Randy P Auerbach, PhD; Phone Number: 646-774-5745; Email: rpa2009@cumc.columbia.edu
• Study Contact Backup: Name: Simryn Molina, BA; Email: simryn.molina@nyspi.columbia.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Northeastern University
      • Contact: Susan Whitfield-Gabrieli, PhD; Email: s.whitfield-gabrieli@northeastern.edu
      • Principal Investigator: Susan Whitfield-Gabrieli, PhD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Randy P Auerbach, PhD; Phone Number: 646-774-5745; Email: rpa2009@cumc.columbia.edu
      • Contact: Randy P Auerbach
      • Principal Investigator: Randy Auerbach, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 13-18 years-old
• Written informed assent/consent and parental/guardian permission for 13-17 year-olds or informed consent for 18 year-olds
• Tanner puberty stage ≥3
• Meets current diagnostic criteria for MDD
• English fluency

Exclusion Criteria:

• Lifetime history of primary psychotic disorders, bipolar disorder, oppositional defiant disorder, conduct disorder, developmental disorder (e.g., autism), post-traumatic stress disorder, or eating disorders
• Substance use disorder, moderate or severe in past 6 months
• Active suicidal ideation with a specific plan
• History of seizure disorder
• Medical or neurological illness (e.g., severe head injury)
• MRI contraindications
• Current psychotropic medication use other than antidepressant medication
• Intelligence quotient (IQ) <80.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 15-Minute mbNF; Participants receiving mindfulness training and 15-minute session of mbNF	Other: Mindfulness + fMRI Neurofeedback; Prior to neurofeedback, participants will receive 45 minutes of mindfulness training. Participants will then receive mindfulness-based fMRI neurofeedback targeting the default mode network and frontoparietal control network.; Other Names: Mindfulness-based Real-time fMRI Neurofeedback
Active Comparator: 30-Minute mbNF; Participants receiving mindfulness training and 30-minute session of mbNF	Other: Mindfulness + fMRI Neurofeedback; Prior to neurofeedback, participants will receive 45 minutes of mindfulness training. Participants will then receive mindfulness-based fMRI neurofeedback targeting the default mode network and frontoparietal control network.; Other Names: Mindfulness-based Real-time fMRI Neurofeedback

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-person Default Mode Network (DMN) Connectivity	DMN change will be assessed via fMRI from before mbNF.	Pre-mbNF procedure
Within-person Default Mode Network (DMN) Connectivity	DMN connectivity will be assessed via fMRI from post mbNF. Changes in DMN connectivity following mbNF are anticipated.	Post-mbNF procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-Report Depression Symptoms	Self-report of depression symptoms from pre-mbNF assessed through the Mood and Feelings Questionnaire; 33-items with each item ranging from 0-2; Higher scores reflect greater depression	Pre-mbNF procedure
Self-Report Depression Symptoms	Self-report of depression symptoms from post-mbNF assessed through the Mood and Feelings Questionnaire; 33-items with each item ranging from 0-2; Higher scores reflect greater depression	Immediately Post-mbNF procedure
Self-Report Depression Symptoms	Self-report of depression symptoms from 1 month after mbNF assessed through the Mood and Feelings Questionnaire; 33-items with each item ranging from 0-2; Higher scores reflect greater depression	1-month
Interviewer-Assessed Depression Symptoms	Depressive symptoms at baseline assessed via the Children's Depression Rating Scale - Revised, which is a clinician interview of depression symptoms. Scores range from 17 to 119 with higher scores reflecting greater depression symptom severity.	Baseline
Interviewer-Assessed Depression Symptoms	Depressive symptoms at 1-month post mbNF assessed via the Children's Depression Rating Scale - Revised, which is a clinician interview of depression symptoms. Scores range from 17 to 119 with higher scores reflecting greater depression symptom severity.	1-month
Self-Reported Rumination	Self-report of rumination symptoms pre-mbNF assessed through the Ruminative Response Scale; 22-items with each item ranging from 1-4; Higher scores reflect greater rumination	Immediately Post-mbNF procedure
Self-Reported Rumination	Self-report of rumination symptoms from post-mbNF assessed through the Ruminative Response Scale; 22-items with each item ranging from 1-4; Higher scores reflect greater rumination	Immediately Post-mbNF procedure
Self-Reported Rumination	self-report of rumination symptoms 1-month post mbNF assessed through the Ruminative Response Scale; 22-items with each item ranging from 1-4; Higher scores reflect greater rumination	1-month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ecological Momentary Assessment of Depression Symptoms	Change in self-report of depressive symptoms from baseline to post-mbNF assessed through the Patient Health Questionnaire (PHQ)-2 delivered via ecological momentary assessment over a 7-day period; 2-items with each item ranging from 0-100; Higher scores reflect greater depression severity.	Immediately Post-mbNF procedure
Ecological Momentary Assessment of Depression Symptoms	Change in self-report of depressive symptoms from baseline to 1-month post-mbNF assessed through the Patient Health Questionnaire (PHQ)-2 delivered via ecological momentary assessment over a 7-day period; 2-items with each item ranging from 0-100; Higher scores reflect greater depression severity.	1-month
Ecological Momentary Assessment of Rumination	Change in self-report of rumination (5-items) from baseline to post-mbNF assessed via ecological momentary assessment over a 7-day period; 5-items with each item ranging from 0-100; Higher scores reflect greater rumination.	Immediately Post-mbNF procedure
Ecological Momentary Assessment of Rumination	Change in self-report of rumination (5-items) from baseline to 1-month post-mbNF assessed via ecological momentary assessment over a 7-day period; 5-items with each item ranging from 0-100; Higher scores reflect greater rumination.	1-month
Ecological Momentary Assessment of Mindfulness	Change in self-report of mindfulness (3-items) from baseline to post-mbNF assessed via ecological momentary assessment over a 7-day period; 3-items with each item ranging from 0-100; Higher scores reflect greater mindfulness.	Immediately Post-mbNF procedure
Ecological Momentary Assessment of Mindfulness	Change in self-report of mindfulness (3-items) from baseline to 1-month post-mbNF assessed via ecological momentary assessment over a 7-day period; 3-items with each item ranging from 0-100; Higher scores reflect greater mindfulness.	1-month
Default Mode Network (DMN) and Frontoparietal Control Network (FPCN) Connectivity	Anticorrelation between DMN and FPCN will be assessed via fMRI from pre and post mbNF. Changes in DMN-FPCN anticorrelation are anticipated.	Immediately Post-mbNF procedure

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Mental Health (NIMH)

Publications and helpful links

General Publications

• Bloom PA, Pagliaccio D, Zhang J, Bauer CCC, Kyler M, Greene KD, Treves I, Morfini F, Durham K, Cherner R, Bajwa Z, Wool E, Olafsson V, Lee RF, Bidmead F, Cardona J, Kirshenbaum JS, Ghosh S, Hinds O, Wighton P, Galfalvy H, Simpson HB, Whitfield-Gabrieli S, Auerbach RP. Mindfulness-based real-time fMRI neurofeedback: a randomized controlled trial to optimize dosing for depressed adolescents. BMC Psychiatry. 2023 Oct 17;23(1):757. doi: 10.1186/s12888-023-05223-8.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 15, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Mindfulness; Major Depressive Disorder; Rumination; Real-time fMRI Neurofeedback
• Additional Relevant MeSH Terms: Mental Disorders; Digestive System Diseases; Gastrointestinal Diseases; Mood Disorders; Feeding and Eating Disorders; Depressive Disorder; Rumination Syndrome; Depressive Disorder, Major; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy; Mindfulness
• Other Study ID Numbers: AAAV1161; R61MH132072-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified data will be uploaded to the NIMH NDA.

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