Optimizing Brain Excitability for Major Depression

Inclusion Criteria: * Men and women, ages 18 to 65 * Diagnosis of major depressive disorder, assessed through a Structured Clinical Interview for DSM-5 (SCID-5) * In a current depressive episode, assessed through a Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (SCID-5) * Moderate-to-severe depression as indicated by a score between 11-20 on the Quick Inventory of Depressive Symptoms (QIDS) * Must comprehend English well to ensure adequate comprehension of the EEG and TMS instructions, and of clinical scales * No current or history of neurological disorders * No seizure disorder or risk of seizures * Neurosurgical patients: Men and women ages 18-65 with medication-refractory epilepsy who are admitted for phase II intracranial monitoring to detect a seizure focus will be considered appropriate for this study. Participants must have the intellectual capacity to understand the consent process and agree to the study. Exclusion Criteria: * Those with a contraindication for MRIs (e.g. implanted metal) * History of head trauma with loss of consciousness * History of seizures or on medications that reduce seizure threshold (e.g., olanzapine, chlorpromazine, lithium) * Neurological or uncontrolled medical disease * Any unstable medical condition * Active substance abuse * Diagnosis of psychotic or bipolar disorder * A prior history of Electroconvulsive Therapy (ECT) failure * History of suicide attempt in the past year * Currently pregnant or breastfeeding * Repetitive Transcranial Magnetic Stimulation (rTMS) treatment in the past six months