Neuroimaging Study for Decoding Emotional States and Identifying Neural Circuits to Disengage From Negative Thinking (RNT-decoding)

The purpose of this study is to decode different thinking states from the brain activation patterns and identify the neural circuits that disengage from these thinking patterns using functional magnetic resonance imaging (fMRI) measurement in individuals with major depressive disorder.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Behavioral: functional magnetic resonance imaging (fMRI)

Detailed Description

This study aims to identify brain activation patterns associated with successful disengagement from negative thinking for MDD-affected participants. The investigators will use a machine learning classifier to decode thinking states from participants' fMRI signals. The decoder is utilized to trace the thinking state's time course as a measure of regulation performance. Investigating the brain activation correlated with the time course of the regulation success can indicate the neural circuits contributing to disengaging from negative thinking. The investigators will also explore the most effective regulation strategy for individual participants. Participants will be instructed to use three regulation strategies: mindfulness by focusing on breathing, distraction with positive thinking, and reinterpretation of a negative thing in a positive way. The investigators expect that the effective strategy could vary across participants, which could be associated with the variability of brain activation patterns in negative thinking.

• Study Type: Observational
• Enrollment (Actual): 89

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Laureate Institute for Brain Research

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Individuals with major depressive disorders

Description

Inclusion Criteria:

• Capable of understanding and complying with protocol requirements.
• Participants who are fluent and literate in English and are able to understand and provide written, informed consent and any required privacy authorization prior to the initiation of any study procedures.
• Male or female, 18 to 65 years.
• Current diagnosis of MDD who are currently depressed defined by the MINI.
• Participants who have moderate depressive symptoms (Patient Health Questionnaire: PHQ-9 ≥ 10 or Quick Inventory of Depressive Symptomatology: QIDS-SR ≥ 11).

Exclusion Criteria:

• Diagnosis of Schizophrenia spectrum or other psychotic disorders.
• Bipolar I Disorder.
• Active suicidal ideation with a plan and intent or suicidal ideation/attempts in the past 6-12 months.
• Current diagnosis of post-traumatic disorder (PTSD) defined by the MINI.
• Change in the dose or prescription of medication within the 6 weeks before enrolling in the study that could affect brain functioning.
• Moderate to severe substance use disorder within the last 12 months.
• A positive test for drugs of abuse, including but not limited to alcohol (breath test), cocaine, marijuana, opiates, amphetamines.
• Use of > 400 mg caffeine or nicotine within the past 2 hours. Medical Conditions
• History of unstable liver or renal insufficiency.
• Significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, hematologic, rheumatologic, or metabolic disturbance.
• Moderate to severe traumatic brain injury or neurocognitive disorders with evidence of neurological deficits.
• Co-morbid medical conditions, including cardiovascular (e.g., history of acute coronary events, stroke) and neurological diseases (e.g., Parkinson's, epilepsy).
• Co-morbid inflammatory disorders (e.g., rheumatoid arthritis, autoimmune disorders).
• Uncontrolled or unstable medical conditions deemed risky by investigators.
• Chronic or acute infectious illness (e.g., HIV, SARS-CoV-2).
• Current use of hormone-containing medications (excluding contraceptives), immunosuppressive medications, non-steroid anti-inflammatory drugs, or analgesics.

MRI Contraindications

• Contraindications for MRI (e.g., metal fragments, cardiac pacemaker). Miscellaneous
• Unwillingness or inability to complete any of the major aspects of the study protocol.
• Non-correctable vision or hearing problems.
• Lack of understanding of English.
• BMI > 40 or < 18.5.
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Classification accuracy of different internal thoughts	fMRI brain images captured during various internal thought processes are used as input to a machine learning classifier. This classifier is trained to discriminate between different mental states. In this context, "classification accuracy" refers to the classifier's ability to accurately identify or predict the specific mental state based on the fMRI data. This measures the classifier's effectiveness in differentiating between mental states by analyzing patterns of brain activity. Classification accuracy is assessed using the area under the receiver operating characteristic curve (AUC), which is robust to imbalances in sample size for each mental state by incorporating the relationship between true positive and false positive rates. A higher AUC indicates better classifier performance.	2 weeks
Changes in blood oxygen level-dependent (BOLD) signals across the whole brain during different internal thoughts and emotion regulation strategies.	Differences in whole brain activation patterns, elicited by various internal thoughts and emotion regulation strategies, will be quantified based on changes in blood oxygen level-dependent (BOLD) signals in the whole brain. An increase in BOLD signal indicates a greater brain activation.	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations of Ruminative Responses Scale (RRS) Brooding subscores with classification accuracy and BOLD signal changes	The RRS Brooding subscale is a self-report scale to measure brooding ruminative responses. A higher score indicates higher brooding ruminative responses with a maximum score of 20 and a minimum score of 5. Classification accuracy and whole brain activation pattern differences in BOLD signals from brain imaging will be correlated with the RRS Brooding subscale.	2 weeks
Correlations of Ruminative Responses Scale (RRS) Depression subscores with classification accuracy and BOLD signal changes	The RRS Depression subscale is a self-report scale to measure depressive ruminative responses. A higher score indicates higher ruminative responses with a maximum score of 48 and a minimum score of 12. Classification accuracy and whole brain activation pattern differences in BOLD signals from brain imaging will be correlated with the RRS Depression subscale.	2 weeks
Correlations of Ruminative Responses Scale (RRS) Reflection subscores with classification accuracy and BOLD signal changes	The RRS Reflection subscale is a self-report scale to measure reflective ruminative responses. A higher score indicates higher ruminative responses with a maximum score of 20 and a minimum score of 5. Classification accuracy and whole brain activation pattern differences in BOLD signals from brain imaging will be correlated with the RRS Reflection subscale.	2 weeks
Correlations of Ruminative Responses Scale (RRS) total score with classification accuracy and BOLD signal changes	The RRS is a self-report scale to measure ruminative responses. A higher score indicates higher ruminative responses with a maximum score of 88 and a minimum score of 22. Classification accuracy and whole brain activation pattern differences in BOLD signals from brain imaging will be correlated with the RRS total scores.	2 weeks
Correlations of Montgomery-Asberg Depression Rating Scale (MADRS) scores with classification accuracy and BOLD signal changes	The MADRS is an interviewer-rated scale to measure the severity of depressive symptoms. A higher score indicates severer depression with a maximum score of 60 and a minimum score of 0. Classification accuracy and whole brain activation pattern differences in BOLD signals from brain imaging will be correlated with the MADRS scores.	2 weeks
Correlations of Hamilton Anxiety Rating Scale (HAM-A) scores with classification accuracy and BOLD signal changes	The HAMA is an interviewer-rated scale to measure the severity of anxiety symptoms. A higher score indicates severer anxiety with a maximum score of 56 and a minimum score of 0. Classification accuracy and whole brain activation pattern differences in BOLD signals from brain imaging will be correlated with the HAM-A scores.	2 weeks
Correlations of Brief State Rumination Inventory (BSRI) scores with classification accuracy and BOLD signal changes	The BSRI is a self-report scale to measure state rumination. A higher score indicates higher state rumination with a maximum score of 800 and the minimum score of 0. Classification accuracy and whole brain activation pattern differences in BOLD signals from brain imaging will be correlated with the BSRI scores.	2 weeks

Collaborators and Investigators

• Sponsor: Laureate Institute for Brain Research, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Actual): December 29, 2025
• Study Completion (Actual): December 29, 2025

Study Registration Dates

• First Submitted: January 26, 2024
• First Submitted That Met QC Criteria: February 8, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 2022-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No