Functional Evidence for Substantia Nigra Pars Reticulata involvement in Auditory Verbal Hallucinations in Treatment-Resistant Schizophrenia

Auditory verbal hallucinations (AVH) in treatment-resistant schizophrenia (TR SZ) are often unresponsive to pharmacologic interventions, necessitating novel therapeutic approaches. We report a case of a patient with persistent AVH who underwent deep brain stimulation (DBS) of the substantia nigra pars reticulata (SNr). To investigate the neurophysiological effects of SNr stimulation on cortical activity during AVH, we performed intraoperative electrocorticography (ECoG) over the left inferior parietal cortex using a 63-channel grid. Real-time recordings captured episodes of AVH and revealed elevated theta-gamma phase-amplitude coupling (PAC), a marker of aberrant cortical synchronization. DBS intervention resulted in normalization of PAC dynamics, with both average PAC and spatial distribution returning to non-AVH levels. Clinically, SNr DBS was associated with a 64% reduction in AVH frequency. These findings provide the first real-time functional evidence linking SNr activity to cortical oscillatory changes underlying AVH. This case supports the potential of SNr as a novel neuromodulatory target in TR SZ and highlights theta-gamma PAC as a candidate biomarker for mechanistic tracking of AVH symptomatology.