Inclusion Criteria:  Primary Diagnostic and Statistical Manuel of Mental Disorders 5 (DSM-V) diagnosis of treatment-resistant Major Depressive Disorder (may have secondary diagnoses of general anxiety, substance disorder)  Non-responders to at least 2 previous anti-depressant medications prescribed by a physician in the past five years Score of ≥20 on Montgomery-Asberg Depression Rating Scale (MADRS) (i.e., moderate to severe depression) All genders aged 21 to 60 years of age Prescribed Ketamine or currently being treated with Ketamine for treatment-resistant Major Depressive Disorder Willing to wear an Electroencephalogram (EEG) headset and an eye mask Willing to listen to ambient sound Willing to have a genetic cheek swab  Exclusion Criteria:  Pregnancy Traumatic Brain Injury within past 3 months Body weight < 50 kg or > 120 kg Coronary heart disease Uncontrolled hypertension as defined in the American College of Cardiology/American Heart Association (ACC/AHA) Hypertension Guidelines Previous contact with Ketamine (therapeutically or recreationally) outside of treatment at the study site Primary psychotic disorder (e.g., schizophrenia, schizoaffective disorder) Bipolar disorder with current manic, hypomanic or mixed state Post-traumatic stress disorder Obsessive-compulsive disorder Primary substance-use disorder Alcohol consumption 24 hours prior and 48 hours subsequent to treatment  Currently using any of the following medications:  Benzodiazepines for 6 hours prior to treatment and 2 hours after treatment Lamotrigine for 6 hours prior to treatment Amphetamine-based stimulants for 6 hours prior to treatment Monoamine Oxidase Inhibitors (MAO-Is) may be taken but blood pressure must be monitored