Surgical treatment of epilepsy and seizures involves recording seizure activity to identify the seizure onset zone
(SOZ), and resecting as much of the SOZ as possible. Existing approaches, such as electrocorticography
(ECoG), define epileptogenic cortex – brain tissue with the potential to initiate seizures – but are inaccurate as
40-60% of patients do not achieve durable seizure freedom after resection/ablation. This outcome gap has
spurred an interest in identifying novel neurophysiological biomarkers to identify brain regions for neurosurgical
intervention to maximize the benefit of epilepsy surgery. Just as the macroscale organization of the epileptic
brain is heterogenous with interconnected brain regions that contribute to seizure initiation and spread, the
microscale organization of epileptogenic cortex is also heterogenous, containing sub-millimeter regions that can
generate microscale inter-ictal activity between seizures. Microscale events may contribute to the generation of
clinical seizures observed at standard macroscales but have not been investigated as they are not detectable in
standard clinical ECoG recordings. Studying microscale events requires microscale µECoG recordings. Under
other support, we have developed a novel electrode array that provides high-density microcontact recording of
microscale events over large cortical areas, ¿1 cm2. The electrode records cortical surface potentials beyond the
resolution and coverage of any currently clinically-available technology.
For this R21 proposal, we propose to initiate a collaboration between a clinician and a neuroscientist-engineer
to develop and test the multiscale properties of seizure networks. We propose to investigate the mechanistic and
clinical implications of microscale epileptiform activity. We will focus on two predictions of the microscale model.
Aim 1 tests the mechanistic prediction that inter-ictal µ-seizures share similar cellular mechanisms as ictal
seizure events. Aim 2 tests the clinical significance of microscale recordings by examining the relationship of µ-
seizures recording intra-operatively to cortex vulnerable to seizure initiation and early propagation identified in
standard clinical recordings. Preliminary intraoperative studies in patients undergoing diagnostic monitoring
demonstrates the feasibility of our approach. This R21 proposal will therefore identify the specific potential value,
mechanistic and/or clinical, of studying microscale interictal events. The results will advance systematic
investigations of the microscale electrophysiology of epileptogenic tissue more broadly.