Repeated Real-time Biofeedback With 7-Tesla MRI for Treatment of Depression

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. The study will assess change in mood and motivation-related measures, as well as neural activity and connectivity changes.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Behavioral: Active Biofeedback; Behavioral: Sham Biofeedback

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. Specifically, this study will aim to extend on prior findings by increasing the sample size and incorporating repeated training sessions to enhance and characterize training effects over time. 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 VTA modulation influences mood and motivation related measures 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: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laurel S Morris, Dr; Phone Number: 01865 (6)16577; Email: laurel.morris@ndcn.ox.ac.uk

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

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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.
• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Mood and Motivation Related Measures	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, PHQ-9, MAP-SR), providing one expected latent mood and motivation factor. Modelling the instruments jointly avoids nominating any single scale as the 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	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

Outcome Measure	Measure Description	Time Frame
VTA Activation	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	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

Outcome Measure	Measure Description	Time Frame
Mood and Motivation EMA	Single-item mood and motivation ecological momentary assessment (EMA). Unit of measure: arbirary likert rating.	Pre to post biofeedback training, within a 6-week timeframe.

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Wellcome Trust
• Investigators: Principal Investigator: Laurel S Morris, Dr, University of Oxford

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2033

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Dopamine; Biofeedback; Brain imaging; 7-Tesla MRI
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depressive Disorder; Behavior; Depression; Depressive Disorder, Major
• Other Study ID 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