Blame Rebalance fMRI Feedback Proof-of-concept (GUIMRINFB1)

Rebalancing Blame Using fMRI Neurofeedback: a Double-blind Controlled Clinical Proof-of-concept Trial in Remitted Major Depressive Disorder

The investigators have shown that decoupling of brain networks when feeling guilty is the first potential functional neuroimaging biomarker of risk of major depression. It remains detectable on remission of symptoms (Green et al., 2012). Decoupling of neural networks was found while people felt guilty during functional magnetic resonance imaging (fMRI) relative to feeling indignation. Guilt-selective brain decoupling is therefore an excellent target for interventions to reduce the largely increased risk of recurrent episodes in people who have had one episode but are currently remitted. To our knowledge, however, there is no proof-of-concept study showing that self-blame-selective decoupling on fMRI can be detected and fed back to the participants after a short temporal delay in a real-time fMRI setting and whether coupling can be increased through neurofeedback training. This project aims at developing the first fMRI neurofeedback system to treat self-blame-selective neural decoupling and to test its feasibility in people with major depressive disorder currently remitted from symptoms.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: GUILT-INCREASE-CORRELATION; Device: GUILT-STABILIZE-CORRELATION

Detailed Description

Specific aim 1: Demonstrate that anterior temporal lobe (ATL)-septal/subgenual cingulate (SCSR) coupling for guilt can be increased through one session of neurofeedback in the group seeing visual feedback based on increasing correlations during the guilt condition compared with the group seeing visual feedback based on keeping correlations at the same level during the guilt condition.

Specific aim 2: Demonstrate that this increase in coupling is selective for guilt relative to indignation.

Specific aim 3: Demonstrate that mood is not negatively affected by neurofeedback.

Specific aim 4: Explore whether this short intervention decreases self-hate on the Interpersonal Guilt Questionnaire (Portuguese translation) and increases self-esteem on the Rosenberg scale (both show significant correlations with SCSR-ATL coupling across major depressive disorder and control groups in our Manchester study), or if these measures are not available, decreases negative affect on the Positive and Negative Affect Scale.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 22290-140
    • Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• past major depressive episode according to Diagnostic Statistical Manual (DSMIV) for at least 2 months, currently not fulfilling criteria for depression and remitted from symptoms for at least 2 months

Exclusion Criteria:

• suicidal thoughts
• other current DSM-IV axis-I disorders
• a history of atypical major depressive episodes (DSM-IV)
• Global Assessment of Functioning scores below 80 as a sign of incomplete remission or co-morbidity
• >2 points on the suicidality item of the Hamilton Depression Scale
• prior criminal convictions
• history of violent behavior towards persons as determined by clinical interview
• positive past or current screening question for irritability on the mood disorders module
• antisocial personality as determined on personality interview using DSM-IV criteria
• borderline personality disorder as determined on personality interview using DSM-IV criteria according to the personality interview
• current self-harming behaviors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GUILT-INCREASE-CORRELATION; Patients in this group will receive visual feedback that reinforces increasing the correlation in fMRI signal between the right superior anterior temporal and septal-subgenual regions during the retrieval of predefined guilt-related autobiographical episodes. During the indignation condition, visual feedback will reinforce stabilization of the preceding degree of correlation.	Device: GUILT-INCREASE-CORRELATION; This uses a novel software "FRIEND" created at IDOR in Rio de Janeiro, Brazil. The software is used on a regular clinical fMRI scanner
Active Comparator: GUILT-STABILIZE-CORRELATION; Patients in this group will receive visual feedback that reinforces stabilization of the preceding degree of correlation in fMRI signal between the right superior anterior temporal and septal-subgenual regions during the retrieval of predefined guilt-related autobiographical episodes. During the indignation condition, visual feedback will also reinforce stabilization of the preceding degree of correlation.	Device: GUILT-STABILIZE-CORRELATION; This uses a novel software "FRIEND" created at IDOR in Rio de Janeiro, Brazil. The software is used on a regular clinical fMRI scanner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase in correlation between anterior temporal and subgenual frontal fMRI signal for guilt relative to indignation	Correlations are computed by using average signal in the most highly activated voxels within a priori regions of interest in the right superior anterior temporal and septal/subgenual cingulate region. The same a priori regions are also used to provide neurofeedback.	change from baseline after one session of fMRI neurofeedback training

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory	This is an outcome measure to ensure the safety of our intervention, we expect that one session of fMRI neurofeedback will not lead to a significant increase in Beck Depression Inventory scores when comparing scores after and before the training session.	Change from baseline after one session of fMRI neurofeedback training
Interpersonal Guilt Questionnaire - Self-hate subscale	This is an exploratory outcome measure to determine whether there is a detectable effect on self-blaming emotions after one session of fMRI neurofeedback. This is not our primary aim in that this study is primarily designed to determine feasibility and safety rather than efficacy.	Change from baseline after one session of fMRI neurofeedback training
Rosenberg Self-Esteem Scale	This is an exploratory outcome measure to determine whether there is a detectable effect on global self-esteem after one session of fMRI neurofeedback. This is not our primary aim in that this study is primarily designed to determine feasibility and safety rather than efficacy.	Change from baseline after one session of fMRI neurofeedback

Collaborators and Investigators

• Sponsor: D'Or Institute for Research and Education
• Investigators: Study Director: Jorge Moll, MD PhD, D'Or Institute for Research and Education; Principal Investigator: Roland Zahn, MD PhD, D'Or Institute for Research and Education; Principal Investigator: Paulo Mattos, MD PhD, D'Or Institute for Research and Education; Principal Investigator: Ricardo de Oliveira-Souza, MD PhD, D'Or Institute for Research and Education; Principal Investigator: Leonardo F Fontenelle, M.D., Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro

Publications and helpful links

General Publications

• Green S, Lambon Ralph MA, Moll J, Deakin JF, Zahn R. Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder. Arch Gen Psychiatry. 2012 Oct;69(10):1014-21. doi: 10.1001/archgenpsychiatry.2012.135.
• Zahn R, Weingartner JH, Basilio R, Bado P, Mattos P, Sato JR, de Oliveira-Souza R, Fontenelle LF, Young AH, Moll J. Blame-rebalance fMRI neurofeedback in major depressive disorder: A randomised proof-of-concept trial. Neuroimage Clin. 2019;24:101992. doi: 10.1016/j.nicl.2019.101992. Epub 2019 Aug 25.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: April 22, 2013
• First Submitted That Met QC Criteria: August 8, 2013
• First Posted (Estimate): August 12, 2013

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: July 21, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: IDOR