Abstracts

Rationale: While neocortical epilepsy is often a focal disease that can be cured through surgical removal of epileptically active regions, other than the electrical activity itself, there are no reliable molecular or anatomic markers that define these foci. We have recently identified a set of molecular markers that correlate precisely to interictal epileptic activities and can hence serve as such markers. Here we have explored the relationship between these epileptic markers, epileptic activities, and the sulcal pattern on patients with medically refractory epilepsy undergoing a 2-stage surgery that includes subdural recording grids.Methods: Ictal and interictal activities were quantified and then mapped onto three-dimensional MRI reconstructions to locate epileptic borders. These electrical borders were then analyzed based on their linear and geodesic distances to other electrodes as a means to define the importance of the sulcal pattern to electrical borders. Neocortical tissues removed from these electrical border zones were then examined from border areas using activity-dependent genes as histological probes to define electrical borders at a cellular level.Results: We found that interictal spiking follows specific anatomic structures and decreases abruptly at anatomic boundaries, such as deep sulci. Histological examination of these boundaries revealed sharp boundaries of activity-dependent gene regulation and signaling pathway activation such as phospho-CREB in specific neuronal populations residing in specific lamina. Conclusions: These results help define the epileptic focus in human neocortex at anatomic and cellular levels that can help explain why epileptic foci both spread to nearby cortex in some regions as well as remain well localized in others.