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 sites 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, precuneus, angular and supramarginal gyri, and functional connectivity to the mediodorsal thalamus, orbitofrontal cortex, anterior cingulate, and dorsolateral prefrontal cortex. These preliminary results highlight specific SNpr subregions and circuits linked to acute symptom reduction, supporting the potential of network-targeted DBS for TR-SZ.

K.A.M has received honoraria from the Parkinson's foundation. All remaining authors do not report potential conflicts of interest.

NCT02361554

K.A.M. received research funding from the National Institutes of Health (NIH) /National Institute of Neurological Disorders and Stroke (NINDS; 5K23NS101096-01A1), Michael J. Fox Foundation, Parkinson's Foundation, UCB Pharma, and Food and Drug Administration (FDA; U01FD005942) and received honoraria from the Parkinson Study Group. M.J.K received research funding from National Institutes of Health (NIH) / University of Pennsylvania School of Medicine as part of T32 Medical Scientist Training Program (MSTP).

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