Neurofeedback for Treatment Resistant Depression

March 3, 2026 updated by: Kymberly Young

Amygdala rtfMRI Neurofeedback for Treatment Resistant Depression

The purpose of this study is to determine the clinical efficacy of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala's response to positive autobiographical memories in patients with depression who are considered treatment-resistant

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond to standard pharmacological and psychological interventions and will be considered treatment resistant (TR-MDD). Decreased reactivity to positive stimuli, indexed by low amygdala reactivity to positive autobiographical memory recall, may be a causal mechanism interfering with recovery from TR-MDD. Previous work in our lab suggests that individuals who do respond to antidepressant medications show increased amygdala activity that is indistinguishable from controls relative to baseline, while TR-MDD individuals fail to show this increase in amygdala activity. Furthermore, the investigators have found that MDD participants (more generally, not specifically TR- MDD) are indeed able to increase their amygdala response during positive memory recall via real-time fMRI neurofeedback (rtfMRI-nf) training, and that this increase is associated with large and rapid reductions in depressive symptoms. Here, the investigators propose to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as an intervention for TR-MDD. 100 TR-MDD individuals will be randomly assigned under double-blind conditions to receive 5 amygdala rtfMRI-nf or 5 control rtfMRI-nf sessions where they are trained to regulate a parietal region putatively not involved in emotional processing or MDD. The investigators will assess changes in amygdala activity, severity of clinical symptoms, and autobiographical memory deficits. Success will suggest a new non- pharmacological, non-invasive intervention for a traditionally treatment-resistant population of MDD individuals.

Study Type

Interventional

Enrollment (Actual)

60

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 Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15261
        • University of Pittsburgh

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

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • right-handed adults (ages 18 - 55) with a primary diagnosis of MDD according to diagnostic criteria DSM-5 for recurrent MDD who are currently depressed will be recruited to participate
  • must be able to give written informed consent prior to participation
  • must have fewer than 45% memories categorized as specific on the Autobiographical Memory Test
  • must have a SHAPS score > 4, indicating the presence of anhedonia
  • unmedicated or stable on an SSRI antidepressant regime (at least 3 weeks to ensure symptoms are stable)
  • previously failed to respond to two previous SSRI medications according to either a medical record review or clinical interview during Visit 1

Exclusion Criteria:

  • have a clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
  • met DSM-IV criteria for alcohol and/or substance dependence (other than nicotine) within 12 months prior to screening
  • have a history of traumatic brain injury
  • are unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
  • are currently pregnant or breast feeding
  • are unable to complete questionnaires written in English
  • current (within 3 weeks of testing) use of any antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications (except SSRI antidepressants) likely to influence cerebral blood flow. Effective medications will not be discontinued for the purposes of the study. Inclusion of patients on stable antidepressant medications was decided in order to allow generalization towards a real world population
  • have a DSM-5 diagnosis of psychotic or organic mental disorder, bipolar I or II disorder or any past or current manic or hypomanic symptoms, autism, or a primary diagnosis of an anxiety disorder (though co-morbid anxiety will not be excluded)
  • have any eye problems or difficulties in corrected vision.

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Amygdala Neurofeedback
attempt to up regulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Five sessions will be performed within a 2 month period.
Device: Amygdala Neurofeedback
Participants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories
Active Comparator: Parietal Neurofeedback
attempt to upregulate the left horizontal segment of the intraparietal sulcus, a region not involved in emotional processing, during positive autobiographical memory recall via real time fMRI neurofeedback. Five sessions will be performed within a 2 month period.
Device: Parietal Neurofeedback
Participants are shown activity from their left horizontal segment of the intraparietal sulcus in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Beck Depression Inventory (BDI-II)
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Amygdala Activity
Time Frame: 8 weeks
% signal change from initial baseline to final transfer run in amygdala activity during ftMRI-nf sessions
8 weeks

Collaborators and Investigators

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

Sponsor

Kymberly Young

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Kymberly Young, PhD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

October 22, 2018

Primary Completion (Actual)

March 1, 2026

Study Completion (Actual)

March 1, 2026

Study Registration Dates

First Submitted

February 1, 2018

First Submitted That Met QC Criteria

February 9, 2018

First Posted (Actual)

February 12, 2018

Study Record Updates

Last Update Posted (Actual)

March 4, 2026

Last Update Submitted That Met QC Criteria

March 3, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY19020313
  • R61MH115927 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The final data set will include self-reported demographic and behavioral data, clinical-rated information regarding illness course, severity, and comorbidities, and brain-imaging data collected during fMRI. The dataset will be stripped of identifiers prior to release for sharing, and will be shared openly and timely in accordance with the most recent NIH guidelines. Data will be shared every six months on the NIH-supported National Database for Clinical Trials Related to Mental Illness (NDCT) data repository.

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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