Spatial Neurophysiological Gradients at High Resolution Differentiate Tumor Types in the Human Cortex at the Tumor-Brain Interface

Brain tumors interact bidirectionally with neural circuits, but direct electrophysiological evidence in the human brain across tumor types remains limited. We analyzed intraoperative clinical, mesoscale, and high-density surface electroencephalography recordings from 100 participants undergoing tumor resection, epilepsy surgery, or deep brain stimulation. Population-averaged measures poorly separated diagnoses, whereas spatially resolved aperiodic exponent and high-gamma activity varied with both tumor distance and nearby tumor volume fraction across scales. Gradients differed among IDH-mutant glioma, IDH-wildtype glioblastoma, and metastases. Connectivity further distinguished infiltrative gliomas: beta coherence across tumor–brain connections was reduced in IDH-mutant tumors (p=0.0006; Kruskal–Wallis; mean coherence: tumor–brain 0.26, tumor–tumor 0.44, brain–brain 0.34), unlike IDH-wildtype tumors or metastases. Physiological abnormalities extended into radiographically normal-appearing brain, indicating tumor-type-dependent physiological signatures that may dynamically map the tumor–brain interface complementing structural imaging, with future possibilities as a spatial biomarker of tumor infiltration and network organization in humans.