Effective stimulation sites and networks for substantia nigra pars reticulata deep brain stimulation for auditory verbal hallucinations in schizophrenia.

Deep brain stimulation (DBS) of the substantia nigra pars reticulata (SNpr) is under investigation for managing auditory-verbal hallucinations (AVH) in treatment-resistant schizophrenia (TR-SZ). We assessed acute AVH suppression during initial SNpr-DBS programming in three TR-SZ patients and mapped associated brain network engagement using normative connectomes. One-month post-implantation, monopolar stimulation at each electrode contact was evaluated for its effect on AVH severity. Volumes of tissue activation (VTA) were integrated with normative structural and functional connectivity data to generate individualized network maps. Among 86 VTAs, stimulation volumes associated with greatest AVH relief localized to left anterior-dorsal and right posterior-ventral SNpr. Greater AVH suppression correlated with structural connectivity to sensorimotor cortex and inferior frontal gyral subregions, and functional connectivity to the insula, orbitofrontal cortex, and dorsolateral prefrontal cortex, regions that fit salience attribution, value/belief updating, and top-down control of source/reality monitoring deficits reported in schizophrenia. These preliminary results highlight specific SNpr subregions and circuits linked to acute symptom reduction, supporting the potential of network-targeted DBS for TR-SZ.