Electrophysiologic Mechanisms of Ketamine Antidepressant Response

Prior treatment

• Sedative or other medication exposure at a level that, in the judgment of the clinical team, precludes safe ketamine administration or reliable behavioral assessment (participant may be deferred rather than permanently excluded if the issue resolves).

Other illness

• Documented IQ \<70, intellectual disability, severe cognitive impairment, delirium, severe aphasia, or other condition that prevents valid consent or task participation.
• Current or past schizophrenia-spectrum disorder or other psychotic disorder.
• Current manic/hypomanic episode or bipolar-spectrum illness judged by study psychiatrist/investigator to increase risk or confound interpretation.
• Imminent suicide risk or active suicidal intent requiring urgent intervention as determined by clinical assessment. Passive ideation without imminent intent may be considered on a case-by-case basis with psychiatric approval and enhanced monitoring.
• Contraindication to subanesthetic ketamine, including uncontrolled hypertension, unstable cardiovascular disease, aneurysm/vascular malformation or similar condition conferring unacceptable risk, pregnancy, breastfeeding, or other clinically significant medical instability.
• Clinical team determination that ketamine administration or study timing would interfere with epilepsy care or perioperative management.

Other

• Active alcohol or substance abuse/dependence within the past 3 months.

• Admitted to the Emory EMU for clinically indicated sEEG monitoring for epilepsy.
• At least mild depressive symptoms at baseline, defined as MADRS ≥7 or BDI-II ≥14.
• Electrode coverage that includes midline regions sufficient for enrollment and analyses.
• Ability to provide informed consent and to complete bedside tasks/questionnaires in English.
• Expected to remain under inpatient monitoring through the planned \~24-hour post-infusion follow-up unless clinical needs dictate otherwise.