Abstracts

Rationale: In in vitro brain slices recording an area of epileptogenicity is surrounded by an enhanced neurophysiological inhibition zone that might limit its spread. It is unclear whether this observation may apply to human epilepsy, too. A typical interictal epileptic discharge (IED) is composed by a sharply contoured wave with a slow afterwave. In experimental epilepsy data the initial sharp wave was thought to be due to Excitatory Postsynaptic Potentials (EPSP) synchronization and the slow afterwave to a subsequent inhibition. Human surface electrocorticography shows a wide range of sharp and slow wave morphologies that can change as a function of the distance from the epicenter. Quantitative measurements of the ratio of the amplitudes of the spike and their corresponding slow wave may show how excitatory and inhibitory processes relate to IED spread and implicate the existence of peripheral inhibition in human epilepsy. Methods: Retrospective analysis was done of electrocorticography recordings from 5 consecutive adult patients in the database of the Comprehensive Epilepsy program of Wayne State University. In 3 patients recordings were done only through subdural strips and grids. In 2 other patients recordings were done also through depth electrodes. Groups of nearly synchronous discharges seen in multiple channels were exported for analysis of amplitudes and ratios of spikes and their corresponding slow waves. The electrode site with the highest amplitude discharge was assumed to approximate the epileptogenic zone epicenter. We have compared the amplitudes of the sharp wave and of the slow afterwave and their ratios in the surrounding electrodes as a function of their distance from the highest spike amplitude electrode. Results: Subdural strips and grids data show that in electrodes adjacent to the highest voltage electrode there is a space-dependent, exponential decrease in the sharp wave amplitude but the slow afterwave amplitude does not show a corresponding decrease or often is even enhanced. The ratio slow wave/sharp wave shows space-dependent enhancement up to 4-11 fold within 2-5 centimeters from the highest voltage electrode. In contrast, depth electrodes located within the white matter showed no obvious space-dependent enhancement of the slow wave as a function of distance from the epicenter. Conclusions: The space dependent enhancement of the slow wave observed only with subdural grids/strips but not with subcortical electrodes, suggests this to be related to the lateral cortical spread of IED. In experimental epilepsy an annulus of cortical inhibition has been observed and thought to limit IED spreading. Our data show a similar phenomenon of peripheral inhibition in human neocortical epilepsy, too. A characterization of its biophysical and molecular mechanisms may allow the identification of novel possible therapeutic targets. We are currently pursuing further analysis in a larger number of patients and also molecular studies in resected tissue from patients with intractable epilepsy to detail such mechanisms.