AI-based discovery of functional boundaries in the human brain from intraoperative electrophysiology.

Neurosurgical and neuromodulation therapies such as deep brain stimulation (DBS) require millimeter-level accuracy to effectively target functional brain regions. Yet, many neuroanatomical boundaries remain invisible to current imaging and electrophysiology methods, limiting precision and contributing to suboptimal patient outcomes. Here, we introduce a self-supervised artificial intelligence (AI) framework that learns to delineate functional subregions directly from the spectral content of intraoperative local field potential (LFP) recordings, without the need for predefined biomarkers or anatomical labels. The framework identifies physiologic structure across the full spectrum of the signal and, through explainable AI (XAI), reveals the specific frequency components underlying these distinctions. Validated in the subthalamic nucleus (STN), the model aligned with clinically defined borders and rediscovered known beta oscillations. Applied to the motor thalamus in tremor patients, it consistently identified functional transitions corresponding to the ventral oralis posterior (Vop) and ventral intermediate (Vim) nuclei-regions where conventional methods fail to provide reliable boundaries. To assess clinical relevance, physiologically defined clusters were functionally evaluated using monopolar review data at their first DBS clinic postoperative visit, demonstrating distinct stimulation-response profiles across clusters and linking electrophysiologic segmentation to clinically meaningful programming outcomes. These findings demonstrate that intraoperative LFP recordings can be transformed into both a real-time guidance resource and a data-driven platform for biomarker discovery, establishing a foundation for more precise, individualized neuromodulation therapies and advancing our understanding of functional brain organization.