Mechanisms of Repeated Real-time Biofeedback With 7-Tesla MRI in Depression

October 29, 2026 updated by: University of Oxford

Previous work demonstrated that individuals are able to self-regulate their ventral tegmental area (VTA) activity using real-time biofeedback. The current study expands this approach to a larger sample with repeated training sessions to more robustly characterize the effects of VTA modulation. This mechanistic study will assess change in mood and motivation-related measures, as well as neural activity and connectivity changes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Major depressive disorder (MDD) is one of the world's largest health problems with current treatments that are ineffective for a substantial proportion of individuals. There is a critical need for mechanistically informed interventions that are individualized and that aim to target core symptoms. Converging evidence from animal and human research in the field has implicated the ventral tegmental area (VTA), a key component of the brain's dopamine system, in regulating motivation and reward-related behaviour. Previous work has demonstrated that participants can successfully train to self-regulate their VTA activity using cognitive strategies while receiving real-time feedback. This shows that VTA self-regulation is feasible in humans. The current study builds on this previous work to further investigate the relationships between VTA activity modulation and mood and motivation related changes in individuals with MDD, in a mechanistic manner. Specifically, this study will aim to extend on prior findings by increasing the sample size and incorporating repeated training sessions. A total of 60 participants with MDD will be recruited and will be randomized in a 1:1 ratio to receive either active biofeedback or sham (control) feedback. Participants will complete two training sessions with real-time 7T-MRI biofeedback. During functional MRI (fMRI) scanning, participants will be trained to use self-generated cognitive strategies to modulate their VTA activity while viewing a visual representation of their brain signal (active condition) or a yoked control signal (sham condition). The primary objective of this study is to determine how variation in VTA modulation is associated with mood and motivation related mechanisms that might change over time. Secondary objectives include assessing changes in VTA activation and functional connectivity over time, as well as examining how neural changes relate to mood and motivation-related changes.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United Kingdom
      • Oxford, United Kingdom, OX39DU
        • Recruiting
        • Oxford Centre for Integrative Neuroimaging (OxCIN) FMRIB, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female aged 18-65 years;
  • Meets DSM-5 criteria for major depressive disorder (MDD) as determined by the Structured Clinical Interview for DSM-5 Axis Disorders (SCID) or the Mini International Neuropsychiatric Interview (MINI); with a current major depressive episode; as conducted in a research-based non-clinical setting.
  • 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:

  • Current or history of schizophrenia or other psychotic disorder, neurodevelopmental disorder, neurocognitive disorder or cognitive impairment
  • Active substance use disorder within the past 1 year;
  • Any unstable medical illnesses;
  • Women who are pregnant;
  • Any contraindications to MRI
  • Antidepressant medication initiated within 2 weeks of the Baseline Assessment and concomitant use of any other medication with central nervous system activity during active participation;
  • Active suicidal intent or plan.

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active Biofeedback

The participants in the active group will receive repeated active biofeedback training sessions.
Behavioral: Active Biofeedback

The active biofeedback session will be done within the 7T MRI. It will include MOTIVATE and active rest trials. During each MOTIVATE trial, subjects will be instructed to generate a heightened state of motivation. Subjects will simultaneously view a progress bar on the screen during MOTIVATE trials that represents their VTA activity and they will be trained to try to increase the level of the bar by motivating themselves.
Sham Comparator: Sham Biofeedback

The participants in the sham group will receive repeated sham biofeedback training sessions.
Behavioral: Sham Biofeedback

The sham biofeedback session resembles the active condition, however, the progress bar seen during the MOTIVATE trials will represent yoked sham values.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mood and Motivation Related Mechanistic Measures
Time Frame: Pre to post biofeedback training, within a 6-week timeframe.

A single composite metric will be derived by factor analysis of a battery of validated mood and motivation related instruments (e.g. PANAS-SF, POMS-SF, MAP-SR), providing one expected latent mood and motivation factor. Modelling the instruments jointly avoids nominating any single scale as the mechanistic outcome, and controls for multiple comparisons. Unit of measure: standardized latent factor score (z / SD units).
Pre to post biofeedback training, within a 6-week timeframe.
VTA Connectivity
Time Frame: Pre to post biofeedback training, within a 4-week timeframe.

Functional connectivity between the VTA seed and whole-brain (voxelwise), measured with 7-Tesla fMRI. Unit of measure: Fisher z-transformed correlation coefficient.
Pre to post biofeedback training, within a 4-week timeframe.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
VTA Activation
Time Frame: Pre to post biofeedback training, within a 4-week timeframe.

Blood-oxygen-level-dependent (BOLD) signal in the bilateral ventral tegmental area (VTA) region of interest for MOTIVATE versus active rest trials, measured with task-based 7-Tesla fMRI. Unit of measure: percent BOLD signal change.
Pre to post biofeedback training, within a 4-week timeframe.
Association between change in VTA measures and change in the mood and motivation factor
Time Frame: Pre to post biofeedback training, within a 6-week timeframe.

The standardized VTA activation and connectivity measure will each be tested for an association with change in the mood and motivation factor. One coefficient is reported per VTA measure. Unit of measure: standardized regression coefficient (dimensionless, from -1 to 1).
Pre to post biofeedback training, within a 6-week timeframe.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mood and Motivation EMA
Time Frame: Pre to post biofeedback training, within a 6-week timeframe.

Single-item mood and motivation ecological momentary assessment (EMA). Unit of measure: arbitrary likert rating.
Pre to post biofeedback training, within a 6-week timeframe.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Oxford

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Wellcome Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Laurel S Morris, Dr, University of Oxford

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2033

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 4, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS IDREC 879781
  • 226532/Z/22/Z (Other Grant/Funding Number: Wellcome Trust)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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