This observational, longitudinal, multi-cohort study aims to evaluate functional brain activity in adults undergoing treatment for Major Depressive Disorder (MDD) at participating clinical sites. A separate cohort of healthy adults will be enrolled as a control group. All data collected in this study are for research purposes only and will not influence clinical decision-making or treatment plans.

This study will use TD-fNIRS to measure hemodynamic brain responses at rest and/or during tasks in patients receiving accelerated transcranial magnetic stimulation (TMS). Imaging will occur at multiple timepoints (pre-treatment, post-treatment, and follow-ups). Healthy control participants will complete similar measurements at one visit, with the option for a follow-up visit. The primary objectives are to assess feasibility, characterize brain activity patterns, and explore potential biomarkers associated with treatment response.

Inclusion Criteria for:

Accelerated TMS cohort

• Adults aged 18-75 at the time of enrollment
• Primary diagnosis of MDD as defined by the DSM-5
• Determined by the clinic to be eligible for accelerated rTMS treatment and agrees to receive accelerated rTMS treatment
• Agrees to start accelerated rTMS treatment in conjunction with study participation to capture baseline measurements
• Has not received rTMS treatment in the past 1 month
• Has not received SPRAVATO treatment in the past 1 month
• Can speak and understand English
• Ability to provide informed consent

Healthy controls cohort

• Adults aged 18-75 at time of enrollment
• Can speak and understand English
• Ability to provide informed consent

Exclusion Criteria for:

All cohorts

• Pregnant or may become pregnant during the treatment course
• Unable or unwilling to wear the fNIRS headset
• Has had electroconvulsive therapy (ECT) in the past 3 months
• Major medical illnesses including neurological and psychiatric conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, schizophrenia, or stroke.
• Any other clinically significant medical condition that in the opinion of the clinician or study team, could affect patient safety, wellbeing, or the participant's ability to comply with study procedures.
• Not an appropriate candidate for the study based on the discretion of the study investigator(s).

Healthy controls cohort only

• Clinical diagnosis of depression in the past year
• Undergoing any treatments for depression in the past year

This study includes two cohorts of adults aged 18-75: (1) participants with a primary diagnosis of Major Depressive Disorder (MDD) who are eligible for and agree to undergo accelerated rTMS treatment, and (2) healthy control participants with no depression diagnosis or depression-related treatment in the past year. All participants must be able to provide informed consent, speak English, and meet general safety and eligibility criteria.