Deep Brain Stimulation to Relieve Depression

Inclusion Criteria: 1. Subject has signed and dated the Screening Consent Form prior to conducting any study-related screening testing 2. Following successful completion of the screening phase, subject has signed and dated the Study Informed Consent Form prior to the initiation of any study-related procedures (other than screening testing). 3. Subject has been medically cleared for DBS neurosurgical procedure by their primary care doctor and study neurosurgeon. 4. Age \>/= 60 years old. 5. Subject is fluent in English (written and verbal). 6. Subject meets Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnostic criteria for major depressive disorder (MDD) based on Structured Clinical Interview for DSM-5 Axis I Disorders (SCID-I) conducted during the screening testing for the project. 7. Subject has medical record documentation that the current major depressive episode (MDE) has persisted for \> 2 years with the exception of brief responses (e.g., \< 8 weeks) to treatments. 8. Subject's depression is treatment resistant; the subject has not clinical responded to 4 or more adequate drug trials of therapy for depression as scored by the antidepressant treatment history form. 1. Three of the 4 trials need to have occurred in the current depressive episode. 2. One of the 4 trials must have included a combination of 2 or more antidepressant medications from 2 different antidepressant classes. 3. One of the 4 trials must have included 1 of the following: augmentation agents: lithium, triiodothyronine, buspirone, bupropion, or atypical antipsychotic. 9. Subject must have tried a course of ECT. 10. Subject's antidepressant medication regimen has been held stable for \> 30 days prior to the study screening MADRS. 11. Subject's screening MADRS score \> 25. 12. Average pre-operative MADRS score of 25 or greater (averaged over at least four weekly pre-surgical evaluations during the weeks prior to surgery) . 13. Aggregate score of \> 8 on the social life and family life/home responsibilities subscales of the Sheehan Disability Scale. 14. Subject has received \> 6 weeks of psychotherapy treatment, for the current or a previous depressive episode, without significant improvement. 15. Female subjects must not be pregnant, and if still of child bearing potential, must agree to a form of medically acceptable contraception. 16. If subject has a vagus nerve stimulator (VNS) implanted, they must agree to have the VNS system removed. 17. Subject agrees to not change psychotropic medication, psychotherapy, and outpatient psychiatric care program regimen throughout the screening phase and for the first six months after implantation of the DBS device. 18. Subject agrees to have the DRIVER investigators be the sole prescriber of psychotropic medications during the course of the study. 19. Evidence of connectivity (tractography identified streamlines) that is not disrupted by a significant burden of white matter hyperintensities between the SCC and nodes that may mediate response to DBS including MFC, dorsal and rostral cingulate, and subcortical nuclei. 20. Availability of an informant is required for study participation Exclusion Criteria: 1. Inability to provide informed consent. 2. Inability to tolerate general anesthesia. 3. Subject has been hospitalized for treatment of depression \< 30 days prior to the screening testing. 4. Active suicidal ideation with intent, suicide attempt within the last six months, or more than three suicide attempts within the last two years. Urgent psychiatric referral will be made in these cases. 5. Subject made a suicide attempt requiring medical treatment \< 3 months prior to the screening testing. 6. Subject has a history of 2 or more suicide attempts \< 12 months prior to the screening testing. 7. Subject poses an imminent suicide risk in the opinion of the investigator. 8. Subject is currently enrolled in or plans to enroll in any concurrent drug and/or device study that may confound the results of this study. 9. Subject has a history of a seizure disorder. 10. Subject will be exposed to diathermy. 11. Subject has a history of a neurosurgical ablation procedure. 12. Subject has a life expectancy of \< 3 years. 13. Significant cerebrovascular risk factors or history of stroke, major head trauma, neurodegenerative disorder, or other general contraindications for DBS surgery (cardiac pacemaker/defibrillator or other Ferromagnetic implanted devices). 14. Contraindication to MRI. 15. Dementia, as defined by Modified Mini Mental State Examination (3MS) \< 84 and clinical evidence of dementia. Patients screened out due to possible dementia will be referred to the local Memory Clinic or Alzheimer's Disease Research Center for evaluation to clarify the presence or absence of dementia. 16. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, obsessive compulsive disorder, panic disorder or post-traumatic stress disorder, or generalized anxiety disorder not secondary to the depression, as diagnosed by the SCID. A recommendation for psychiatric referral will be made in these cases. 17. Substance misuse (except for nicotine or caffeine) not in full sustained remission for at least one year as determined by SCID, and confirmed by study physician interview. 18. Anticoagulant pharmacotherapy. 19. Subjects that are determined during the screening phases to have severe personality disorders may be excluded. 20. Final patient selection will be made by consensus of the multidisciplinary study team. No exclusion criteria are based on race, ethnicity, or gender.