The second DBS trial in ultra-resistant schizophrenia is out of Johns Hopkins University where the study team led by Dr. William Anderson will be recruiting three ultra-refractory patients and will be targeting the local inhibition of the substantia nigra pars reticulata (SNr), a major outflow nucleus of the basal ganglia with the intention of disinhibition and driving the activity of the mediodorsal nucleus of the thalamus (Clinicaltrials.gov Identifier: NCT02361554). The structure and hypofunction of the mediodorsal nucleus of the thalamus has been investigated in several imaging and post-mortem studies in schizophrenia (208). All of the DBS studies in ultra-resistant schizophrenia are only recruiting those patients who have exhausted all other therapeutic alternatives and continue to have severe and disabling clinical symptoms and poor functioning.