 Despite many available treatments, there are patients with major depression who remain treatment refractory and chronically disabled. For these severely ill patients, several neurosurgical procedures are available where brain lesions are made that interrupt white matter tracts linking orbital frontal cortex to the striatum, resulting in significant therapeutic benefit for many patients. In this study, we will test the safety and efficacy of Deep Brain Stimulation DBS--a reversible method used to modulate brain activity--as an alternative to the standard subcaudate tractotomy SCT. The physiological consequences of this procedure will be mapped longitudinally using positron emission tomography PET measures of brain glucose metabolism. Patients will be clinically monitored for 1 year with longitudinal psychiatric, neurological, neurosurgical, neuropsychological and PET imaging examinations to assess treatment efficacy and side effects. 