Decoding Emotional Dynamics in Bipolar Disorder

NCT07221864 | Recruiting DMC

• 2 other identifiers: 2025-0055P20GM121312-08
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this neuroimaging study is to investigate how emotional states fluctuate in people with bipolar disorder (BD) compared to healthy controls, and to understand the neural mechanisms driving mood instability. The main questions it aims to answer are:

• Can emotional states be decoded from fMRI brain activity using machine learning?
• Do individuals with BD show more unstable emotional state trajectories (e.g., high metastability, low fractal scaling) than healthy controls?
• Does amplifying positive emotions stabilize brain and emotional dynamics in BD? Researchers will compare individuals with bipolar disorder (BD-I or BD-II, currently depressed or mixed state) to healthy controls without psychiatric history to see whether the BD group shows greater fluctuations in emotional brain activity and whether positive emotion regulation strategies normalize this instability. Participants will:
• Complete self-report questionnaires on mood, emotion regulation, anxiety, and daily functioning.
• Recall and provide short descriptions of personal positive and negative memories to be used in the MRI task.
• Undergo fMRI scanning, including:
• Resting-state scans
• A Think and Regulate Affective States Task (TReAT) where they recall autobiographical memories, rate emotions, and practice amplifying positive mood.
• Structural and diffusion MRI for brain mapping.
• Receive physiological monitoring (heart rate, respiration) during scanning.
• Complete post-scan surveys on emotional state and task experience. This research will help clarify how the brain supports or disrupts emotional regulation in bipolar disorder and may inform the development of personalized, neurobiologically informed treatments for mood instability.

Conditions

Bipolar Disorder I or II; Healthy (Controls)

Keywords

neuroimaging; fMRI; Bipolar Disorder I; Bipolar Disorder II; machine learning; emotion regulation

Outcome Measures

Primary Outcomes (2)

• Decoded Emotional State Trajectory

  The decoded emotional state time course derived from fMRI during the Think and Regulate Affective States Task (TReAT). Temporal irregularity will be quantified using permutation entropy to assess emotional state instability in individuals with bipolar disorder compared to healthy controls.

  Day 2

• Metastability of brain network states

  Metastability of brain network states will be calculated from whole-brain fMRI data to characterize variability in emotional states.

  Day 2

Secondary Outcomes (2)

• Brain regional contributions to the transition energy of emotional brain state changes

  Day 2

• Fractal scaling of brain state changes

  Day 2

Study Arms (1)

Decoding Emotional Dynamics

EXPERIMENTAL

All participants complete the same two-session protocol: a preparation visit with diagnostic interviews and questionnaires, followed by an MRI session including resting-state and task-based scans. During the Think and Regulate Affective States Task (TReAT), participants recall personal positive and negative memories, rate their emotions, and practice positive emotion amplification strategies. Physiological signals are recorded throughout. Both individuals with bipolar disorder and healthy controls complete identical procedures for comparison of brain and emotional dynamics.

Behavioral: Think and Regulate Affective State Task

Interventions

Think and Regulate Affective State Task BEHAVIORAL

Participants complete the Think and Regulate Affective States Task (TReAT) during fMRI scanning. This task presents brief cues of participants' own autobiographical memories, four positive and four negative, to evoke corresponding emotional states. While viewing these cues, participants alternate between thinking about the memory, rating emotional valence and arousal, and practicing positive emotion amplification strategies. Each session includes multiple blocks of "Think," "Rate," "Regulate," "Attention," and "Rest" periods. Physiological measures (heart rate and respiration) are recorded concurrently. The task is designed to decode emotional states from fMRI data and evaluate the neural impact of positive emotion regulation in bipolar disorder compared to healthy controls.

Decoding Emotional Dynamics

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years
• Male or female
• BMI between 18.5 and 38.0 kg/m2 at Screening
• Capable of understanding and complying with study requirements
• Fluent in English
• Able to provide informed consent
• BD Group:
• Meet the DSM-5 diagnostic criteria for BD-I or BD-II who are currently depressed or mixed state defined by the Mini-International Neuropsychiatric Interview (MINI)
• Moderate or greater depressive symptom severity (MADRS ≥ 15 or PHQ-9 ≥ 10)
• HC Group:
• No current or past psychiatric disorder (verified by MINI)

You may not qualify if:

• No telephone or easy access to a telephone
• Significant medical problems as identified by the medical screening questionnaire: e.g. a history of unstable liver or renal insufficiency; glaucoma; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments
• A positive test for drugs of abuse, including alcohol (breath test), cocaine, opiates, amphetamines, methamphetamines, phencyclidine, benzodiazepines, barbiturates, methadone, and oxycodone
• Drug or alcohol intoxication (based on positive UTOX or breathalyzer test at screening or study session) or reported alcohol/drug withdrawal, last cannabis use must be \>48 hours prior to study session.
• Current DSM-5 diagnosis of a psychosis spectrum disorder or moderate to severe substance use disorder
• Moderate to severe traumatic brain injury or other neurocognitive disorder with evidence of neurological deficits, neurological disorders, or severe or unstable medical conditions that might be compromised by participation in the study (to be determined by primary care provider)
• Current significant suicidal ideation or suicide attempt within the past 3 months.
• Change in the dose or prescription of a medication within the 6 weeks before enrolling in the study that could affect brain functioning, e.g., anxiolytics, antipsychotics, antidepressants, or mood stabilizers
• Taking drugs that affect the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, excessive caffeine intake \> 1000 mg/day)
• MRI contraindications as documented on the MR Environment Screening
• Unwillingness or inability to complete any of the major aspects of the study protocol, including magnetic resonance imaging (i.e., due to claustrophobia), or behavioral assessment. However, failing to complete some individual aspects of these assessment sessions will be acceptable (i.e., being unwilling to answer individual items on some questionnaires or being unwilling to complete a behavioral task)
• Non-correctable vision or hearing problems

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74135, United States

RECRUITING

Related Publications (16)

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• Misaki, M., et al. Decoding Temporal Dynamics of Emotion Regulation: Reinterpretation, Distraction, and Mindfulness. in OHBM 2025 - Annual Meeting Organization for Human Brain Mapping. 2025. Brisbane, Australia.

  BACKGROUND

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MeSH Terms

Conditions

Bipolar Disorder; Emotional Regulation

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Self-Control; Social Behavior; Behavior

Central Study Contacts

Masaya Misaki Study Primary Investigator, Ph.D.

CONTACT

918-502-5137; mmisaki@laureateinstitute.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Investigator

Study Record Dates

• First Submitted: October 23, 2025
• First Posted: October 28, 2025
• Study Start: October 30, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Access Criteria: Qualified researchers with approved data use agreements may request access through the National Institute of Mental Health (NIMH) Data Archive (NDA). Access requires institutional affiliation, completion of the NDA Data Use Certification process, and agreement to comply with all confidentiality, security, and ethical use requirements. Data will be shared only in de-identified form through the NDA's secure access system; no direct identifiers or contact information will be provided.

Locations

US (1)