Spatiotemporal Correlations of Mesoscale Neocortical Activities in Patients with Focal Epilepsy

Brain function is reflected in both the action potentials of individual neurons and interactions through e.g. synaptic currents reflected in widespread, slow fluctuations of the local field potential (LFP). We analyzed microelectrode array data to determine state-dependent correlations between action potential and LFP during seizure events as well as interictally in patients with focal epilepsy. We also examined activity in two different cortical network territories: the seizure core and surrounding penumbra (Schevon et al., 2012). The cross-correlation of spiking activity in the core showed an association of the ictal action potentials with the global oscillatory aspect of the seizure activity and indicated local failure of inhibitory restraint surrounding the ictal spike. These patterns were not observed in the penumbra. Our analyses from clinical recordings and a model of a single ictal spike in the core revealed that both the temporal and spatial components of the network’s cross-correlation can be approximated by a sine cardinal ( sinc ) function. The biological interpretation of these findings is that important functional differences across the neocortical network exist, with a critical role of the millimeter-range excitatory connections within the grey matter. Therefore, localized intervention that prevents escape of hyperactivity from the seizure core may be considered as a therapeutic strategy. Significance Statement Analysis and modeling of spatiotemporal cross-correlation between multi-unit spike activity and the local field potential of human seizure activity demonstrates a difference of network functionality between the seizure core and its surrounding penumbral network. In this study, we show that millimeter-range excitatory connections, known to exist within the gray matter of neocortex, play a critical role in propagating the effects of ictal hyperexcitation. These findings contribute to our understanding of ictal mechanisms and hold promise for further development of strategies to detect the ictal core territory and prevent seizure propagation.