Introduction: Electrophysiological signals exhibit both periodic and aperiodic properties. Periodic oscillations are associated with numerous physiological and cognitive processes. Emerging evidence demonstrates that the aperiodic component 1/f slope represents putative physiological interpretations, including excitation-inhibition (E/I) balance estimations. Our study analyzes the power spectral density's aperiodic component (1/f slope) of the glioma-infiltrated cortex to evaluate E/I imbalance across glioma subtypes.
Methods: Resting-state intraoperative electrocorticography data were obtained from glioma patients and processed for spectral analysis. Each electrode’s 1/f slope was calculated within the 70-150 Hz high-gamma frequency range. Electrodes were classified as tumor-infiltrative or normal-appearing based on preoperative MRI T2-FLAIR signal. Linear mixed-effects modeling compared 1/f slopes between tumor and non-tumor regions and examined subtype-specific shifts in E/I balance. Our electrophysiological analysis was validated with single nucleus RNA sequencing of spatially annotated glioma tissues.
Results: The study cohort consisted of 660 electrodes (77.1% normal appearing; 22.9% tumor-infiltrated) from 13 patients (30.8% female) with a mean age of 45.8 years. Glioma subtypes comprised 7.7% WHO grade 2-3 IDH mutant oligodendroglioma, 46.2% WHO grade 2-3 IDH mutant astrocytoma, 38.4% glioblastoma, and 7.7% diffuse midline glioma (DMG). Tumor-infiltrative electrodes demonstrated a significantly lower 1/f slope compared to normal-appearing electrodes (p < 0.001), suggesting a shift towards an excitation dominance state. When stratified by glioma subtype, normal-appearing electrodes in glioblastomas exhibited a significantly lower 1/f slope compared to astrocytomas (p=0.019) and oligodendrogliomas (p=0.012), suggesting that the E/I imbalance may extend beyond visible glioma infiltration. Within tumor-infiltrative regions, glioblastomas and DMGs had significantly lower 1/f slopes compared to astrocytomas and oligodendrogliomas (GBM: p< 0.001; DMG: p< 0.001). Single nucleus RNA sequencing confirmed an excitation transcriptomic profile within regions of cortical infiltration.
Conclusion : Glioblastomas and DMGs are associated with an excitation state determined by a 1/f slope. The 1/f slope may serve as a physiologically relevant measure of E/I imbalance in glioma.
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