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

• ClinicalTrials.gov Identifier: NCT01920490
• Recruitment Status: Completed
• First Posted: August 12, 2013
• Last Update Posted: July 23, 2015
• Sponsor: D'Or Institute for Research and Education
• Information provided by (Responsible Party): D'Or Institute for Research and Education

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Device: GUILT-INCREASE-CORRELATION; Device: GUILT-STABILIZE-CORRELATION	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Rebalancing Blame Using fMRI Neurofeedback: a Double-blind Controlled Clinical Proof-of-concept Trial in Remitted Major Depressive Disorder
• Study Start Date: May 2013
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Increase in correlation between anterior temporal and subgenual frontal fMRI signal for guilt relative to indignation [ Time Frame: change from baseline after one session of fMRI neurofeedback training ]
   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.

Secondary Outcome Measures :

1. Beck Depression Inventory [ Time Frame: Change from baseline after one session of fMRI neurofeedback training ]
   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.
2. Interpersonal Guilt Questionnaire - Self-hate subscale [ Time Frame: Change from baseline after one session of fMRI neurofeedback training ]
   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.
3. Rosenberg Self-Esteem Scale [ Time Frame: Change from baseline after one session of fMRI neurofeedback ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Brazil

Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro

Rio de Janeiro, Brazil, 22290-140

Sponsors and Collaborators

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

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: D'Or Institute for Research and Education
• ClinicalTrials.gov Identifier: NCT01920490
• Other Study ID Numbers: IDOR
• First Posted: August 12, 2013
• Last Update Posted: July 23, 2015
• Last Verified: July 2015

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms