Routing to the seizure in postoperative human glioma cortex: spatio-temporal uncoupling between slow and fast extracellular neuronal activities

BACKGROUND: Diffuse gliomas are frequently associated with epilepsy, particularly in low-grade variants. Seizures are key events to be considered in glioma management, including during surgery. Optimizing resection of epileptic areas may affect not only postoperative epilepsy but also glioma prognosis in the context of interactions between glioma growth and neuronal activities. As for glioma tissue resection, surgery of epileptic networks requires a deeper understanding of their organization and reliable biomarkers. METHODS: We investigated the spatiotemporal dynamics of the transition from interictal to ictal-like events (ILEs) using ex vivo human peritumoral tissue from glioma patients. Slices were recorded with multi-electrode arrays during the transition from the spontaneous interictal state to pharmacologically induced seizures considering the dynamics of slow versus fast oscillatory neuronal activities. RESULTS: Transition to seizure was characterized by the emergence of preictal discharges (PIDs), allowing subdivision of the preictal phase into build-up, steady-state, and trigger periods. PIDs progressively increased in amplitude, duration, and slope with significant changes during the trigger phase. Concurrently, high-frequency activity (180-550 Hz) and high-frequency oscillations (HFOs) increased across the transition period, particularly during the trigger phase. In addition to such preictal recruitment, the reinforcement of HFOs was accompanied by a spatial organization in additive microdomains, peaking at seizure onset and encompassing slow field potential dynamics. CONCLUSIONS: In the periglioma human cortex, seizures arise from progressively recruited neuronal assemblies sculpted together with HFOs, providing new insights into the microphysiological processes of glioma-related ictogenesis and requiring consideration of the preictal fast and focal neuronal activity.