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    Area of Science:

    • Neuroscience
    • Psychiatry
    • Medical Technology

    Background:

    • Auditory verbal hallucinations (AVH) are a persistent challenge in treatment-resistant schizophrenia (TR SZ).
    • Pharmacological treatments often fail to alleviate AVH, highlighting the need for innovative therapeutic strategies.
    • Deep brain stimulation (DBS) is an emerging neuromodulatory technique with potential applications in complex psychiatric disorders.

    Purpose of the Study:

    • To investigate the neurophysiological effects of substantia nigra pars reticulata (SNr) DBS on cortical activity during AVH.
    • To explore the role of theta-gamma phase-amplitude coupling (PAC) as a biomarker for AVH.
    • To assess the clinical efficacy of SNr DBS in reducing AVH frequency in a patient with TR SZ.

    Main Methods:

    • A case study involving a patient with persistent AVH undergoing SNr DBS.
    • Intraoperative electrocorticography (ECoG) using a 63-channel grid over the left inferior parietal cortex during AVH episodes.
    • Real-time analysis of theta-gamma PAC dynamics and correlation with AVH frequency and severity.

    Main Results:

    • Real-time ECoG recordings identified elevated theta-gamma PAC during AVH episodes, indicating aberrant cortical synchronization.
    • SNr DBS intervention led to the normalization of theta-gamma PAC dynamics, both in average coupling and spatial distribution.
    • The patient experienced a significant 64% reduction in AVH frequency following SNr DBS.

    Conclusions:

    • This study provides the first real-time functional evidence linking SNr activity to cortical oscillatory changes associated with AVH.
    • SNr DBS demonstrates potential as a novel neuromodulatory target for managing AVH in TR SZ.
    • Theta-gamma PAC serves as a promising candidate biomarker for mechanistic tracking of AVH symptomatology during therapeutic interventions.