• Men and women (non-pregnant) between ages 22 and 70;

• DSM-5 diagnosis (assessed by Structured Clinical Interview for DSM-5 Axis I disorders SCID-5) of major depression disorder (MDD) as the primary diagnosis. A current major depressive episode (MDE), recurrent or single episode with first episode before age 60, secondary to nonpsychotic unipolar major depressive disorder;

• Chronic illness with current MDE ≥24 months duration and/or recurrent illness with at least a total of 2 lifetime episodes (including current episode \>12 months);

• Treatment resistance (defined by criteria on the Antidepressant Treatment History Form ATHF): Failure (i.e. persistence of the major depressive episode) to respond to a minimum of four adequate depression treatments from at least two different treatment categories (e.g. SSRIs, SNRIs, TCAs, other antidepressants, lithium-addition, irreversible MAOIs, antidepressant augmentation with an atypical antipsychotic medication);

• Previous trial of Electroconvulsive Therapy (ECT) (lifetime): either did not respond, relapsed, poorly tolerated or refused. If refused, will discuss reasons and ensure subject understands relative risks of ECT versus DBS. We will try to enrich sample with patients who had previously shown response to ECT (or another intervention) that was partial or un-sustained;

• Symptom severity for Screening: Hamilton Depression Rating Scale-17 item (HDRS17) ≥20;

• The HDRS17 must remain greater than or equal to 20 on two separate assessments (at initial screening and 1 week before surgery), over a 1-month period;

• Symptom severity for Outcome: Montgomery Asberg Rating Scale (MADRS) ≥27 to be met at assessment one-week pre-op;

• Lifetime exposure to minimal 6 weeks of psychotherapy without sustained response;

⁃ Must have a brain MRI within 3 months of enrollment that is normal, according to the radiology report, or does not reveal any findings that in the opinion of the Investigator preclude participation in the study;

⁃ Stable antidepressant medication regimen for the month preceding surgery;

⁃ Modified mini-mental state examination (MMSE) score ≥ 24;

⁃ Normal thyroid stimulating hormone (TSH) level within 12 months of study entry;

⁃ The patient does not have any medical or physical conditions which, in the opinion of the Investigator, make it unlikely the patient will be able to participate for the duration of the study;

⁃ Able and willing to give informed consent and agree to attend regular clinic visits for at least 12 months following surgery;

⁃ Must have a treating psychiatrist, a family member, significant other/living partner, a caregiver, or a person known by the subject present at the Screening visit for the discussion about the study before co-signing the informed consent form;

⁃ Willingness to sign Treatment Contract;

⁃ Agrees to be followed at regular intervals by a licensed psychiatrist and to provide written permission allowing any and all forms of communication between the research team and the subject's healthcare providers, for the entirety of the study.