Capturing remote activation of epilepsy source?

Abstract

Spontaneous focal synchronization of collective spiking followed by induced traveling waves can occur in the cortical sheet and in cultured planar neuronal networks. In the first case, it is well-known focal epilepsy leading to a seizure and, in the second, this synchronization originates from one of a few steady nucleation sites resulting in a so-called population spike. Assuming functional similarity between the nucleation sites and non-lesional epileptic foci, the major unsolved problem in both cases is that it is unclear whether activation of the focus originates internally (i.e., autonomously relative to interaction with surrounding neuronal tissue) or externally. The internal scenario implies that the focus spatially contains some pacemakers. In turn, several experimental findings indicate a complex spatially non-local activation of epileptic focus. Here, we suggest a generative mechanistic model of planar neuronal network, where the spatial configuration of pacemaker neurons is artificially engineered in order to resolve the above mentioned problem: all pacemakers are placed within a circular central spot. Leaving the global dynamic regime unaffected, this crucially helps to clarify the activation process, visualizing of which is hindered in the natural spatially-uniform configuration. We show in simulations that the nucleation sites (i) can emerge in spatial regions, where pacemakers are completely absent and (ii) can be activated even without direct links from pacemakers. These results demonstrate the principle possibility of external, or remote, activation of a focal source of epileptic activity in the brain. The suggested deterministic model provides the means to study this network phenomenon systematically and reproducibly.