Abstract
<jats:p>We report a pilot study of deep brain stimulation (DBS) in three individuals with treatment refractory schizophrenia (TRS). DBS target selection was supported by an inpatient brain network mapping paradigm using intracranial electroencephalography. In conjunction with assessing stimulation-dependent symptom improvement, we derived spatiotemporally resolved profiles of psychosis and healthy brain states and identified stimulation targets that best shifted brain networks towards healthy states. Therapeutic stimulation sites were personalized for each participant but converged on salience network nodes including anterior cingulate and anterior insula. No significant adverse events were noted across participants. Moreover, two participants with chronic stimulation and clinical follow-up of at least 4 months reported significant improvement in both positive and negative symptoms, and treatment optimization is underway for the third. These critical pilot data establish the feasibility of personalized DBS guided by concurrent stimulation mapping, behavioral assessment, and biomarker monitoring as a treatment for TRS.</jats:p>