Optimizing Brain Excitability in 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