Abstract: Cortical targets represent important nodes within the neural networks that subserve psychiatric disorders.Although more invasive, surgical cortical stimulation allows for stimulation with increased spatial specificity.Current paradigms utilize electrodes implanted epidurally rather than subdurally, as the dura provides a barrier that increases the activation threshold of neural tissue, and reduces the risk of induced seizure (Bezard et al., 1999).Furthermore, the implantation of electrodes epidurally significantly decreases the risk of irritating or damaging underlying brain tissue, and eliminates the risk of subdural hematoma as well as cerebrospinal fluid leak.The mechanism of action of ICS is still poorly understood, particularly for psychiatric disorders in which neurophysiologic underpinnings are often ill defined. Depression Review of StudiesWe conducted a prospective, longitudinal single-blinded analysis of the effect of epidural stimulation of the left DLPFC in patients with severe treatment-resistant depression (Kopell et al., 2011).The study included 12 patients, followed over the course of 104 weeks with the main outcome measure defined as at least a 40% decrease in the Hamilton-Depression Rating Scale -28 (HDRS).As this was primarily designed to be a safety and feasibility study, only the subjects were blinded to the stimulation state during an 8-week sham-controlled phase.Patients selected were limited to those with the most severe, refractory depression and met a rigid series of inclusion and exclusion criteria (Table 14.1).Electrodes were implanted unilaterally through a small craniotomy, and consisted of a paddle with two platinum-iridium contacts 3.75 in diameter and spaced 15mm apart (Fig. 14.1A).In addition to HDRS, the study also measured response in the Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire.Subjects were followed every two weeks from implantation to week 16, and subsequently every four weeks until week 104 with a variety of the above tests and, at pre-set intervals, the addition of a Mini-Mental Status Exam (MMSE) and repetition of the baseline neuropsychological battery.Moreover, PET scanning was performed at baseline, and in a treated state.Of note, one patient was excluded from the analysis because of a violation in study-protocol during the baseline period.After 8 weeks of active, continuous stimulation (week 8 for the study group, and week 16 for the sham-controlled stimulation group), the subjects entered an "adaptive protocol" and settings were adjusted based on subject response with