The Quest for Seizure Freedom: Epileptogenic tissue mapping with intraoperative electrocorticography

Epilepsy surgert offer the chance of seizure freedom, but only if we can find and remove the exact part of the brain network causing the seizures. Pinpointing the location of epileptic tissue remains challenging. Routine tests such as scalp EEG and MRI are essential but often incomplete: subtle brain abnormalities can be missed, or a visible lesion may not match the true epileptic tissue. Intraoperative electrocorticography (ioECoG) helps to address this gap. IoECoGs are typically recordded using a grid electrode: a flexible sheet of silicone with electrodes placed on the exposed brain. IoECoG recordings are interpreted in real time, allowing the surgical
plan to be adjusted immediately, with the goal of removing as much epileptic tissue as possible while sparing healthy brain areas. The interpretation of ioECoG relies on epileptic biomarkers: spikes and high-frequency
oscillations (HFOs). Spikes are brief discharges indicating irritated tissue but are not always specific for epileptic tissue. HFOs are newer biomarkers that reflect very fast brain activity above 80Hz, divided into ripples (80–250Hz) and fast ripples (250–500Hz). Ripples can occur in both healthy and epileptic tissue, whereas fast ripples are more
specific to epileptic tissue, but they are small in amplitude and often missed.
My thesis explores how these biomarkers relate to epileptic tissue, how they can help guide the neurosurgeon, and how new technology can enhance their use. Part I focuses on biological origins. In Chapter 2, ioECoG recordings from patients with low-grade tumors showed that tissue with inflammation markers produced ripples,
suggesting an association between the inflammatory processes and the generation of fast oscillatory activity by the brain. In Chapter 3, I found that in focal cortical dysplasia, spikes and HFOs co-occurred in epileptic areas, forming a more specific fingerprint of epileptogenic tissue than either signal alone. Part II examines clinical applications. In Chapter 4, children who showed cognitive improvement after epilepsy surgery had few remaining fast ripples and a strong reduction in pathological ripples, suggesting that epileptic HFOs relate to cognitive recovery potential. Chapter 5 showed that pausing anesthetic medication uring surgery is safe to perform ioECoG recordings. Part III focuses on new technology in ioECoG. In Chapter 6 ioECoG is introduced into oncological neurosurgery. Based on IoECoG-guided glioma surgeries we demonstrated that residual spikes after tumor removal were associated with seizure recurrence. Importantly, histopathology revealed that brain regions producing spikes were always infiltrated by tumor cells, even when MRI appeared normal, highlighting
spikes as markers of both epileptogenic and infilltrated tissue. Finally, Chapter 7 explores innovations in ioECoG technology. I implemented high-resolution grids with four times more electrodes and demonstrated that this high-resolution grid recorded highly localized spikes and HFOs that were missed by standard grids. These detailed
recordings improved identification of spike onsets.
This thesis shows how ioECoG helps to translate the brain’s electricity into personalized epilepsy care. By incooporate electrophysiology information, we can better identify the faulty wiring and restore balance—bringing us closer to tailored treatments and a future in which more patients live free from seizures.