The success of deep brain stimulation (DBS) for treating movement disorders such as Parkinson’s disease has led to its application to several other disorders, including treatment-resistant depression (TRD). Results of trials using DBS to treat TRD have been heterogeneous, with inconsistencies largely driven by incomplete understanding of the brain networks regulating mood, especially on an individual basis. We recently embarked on an NIH-funded trial designed to investigate the neurophysiological basis of mood and cognitive disruption in TRD in order to individualize therapy and thereby hopefully improve outcomes. To do so, we adapted an approach commonly used in epilepsy surgery – individual-specific intracranial recording and stimulation – to the study of TRD. The intracranial platform allows us to understand the neurophysiological underpinnings of mood states and the network’s response to stimulation. With this information in hand, we may be able to more readily tailor DBS therapy to symptomatic networks and improve the consistency of response. I will present our initial results from this trial, both in terms of clinical outcomes and efforts with decoding mood state from intracranial neurophysiology.