Neuroimaging Study for Decoding Emotional States and Identifying Neural Circuits to Disengage From Negative Thinking

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.

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.

Eligibility Criteria:
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.