Changes in corticocortical and corticohippocampal network during absence seizures in WAG/Rij rats revealed with time varying Granger causality.

PURPOSE: Spike-and-wave discharges (SWDs) recorded in the cortical EEGs of WAG/Rij rats are the hallmark for absence epilepsy in this model. Although this type of epilepsy was long regarded as a form of primary generalized epilepsy, it is now recognized that there is an initiation zone - the perioral region of the somatosensory cortex. However, networks involved in spreading the seizure are not yet fully known. Previously, the dynamics of coupling between different layers of the perioral cortical region and between these zones and different thalamic nuclei was studied in time windows around the SWDs, using nonlinear Granger causality. The aim of the present study was to investigate, using the same method, the coupling dynamics between different regions of the cortex and between these regions and the hippocampus.

METHODS: Local field potentials were recorded in the frontal, parietal, and occipital cortices and in the hippocampus of 19 WAG/Rij rats. To detect changes in coupling reliably in a short time window, in order to provide a good temporal resolution, the innovative adapted time varying nonlinear Granger causality method was used. Mutual information function was calculated in addition to validate outcomes. Results of both approaches were tested for significance.

RESULTS: The SWD initiation process was revealed as an increase in intracortical interactions starting from 3.5s before the onset of electrographic seizure. The earliest preictal increase in coupling was directed from the frontal cortex to the parietal cortex. Then, the coupling became bidirectional, followed by the involvement of the occipital cortex (1.5s before SWD onset). There was no driving from any cortical region to hippocampus, but a slight increase in coupling from hippocampus to the frontoparietal cortex was observed just before SWD onset. After SWD onset, an abrupt drop in coupling in all studied pairs was observed. In most of the pairs, the decoupling rapidly disappeared, but driving force from hippocampus and occipital cortex to the frontoparietal cortex was reduced until the SWD termination.

CONCLUSION: Involvement of multiple cortical regions in SWD initiation shows the fundamental role of corticocortical feedback loops, forming coupling architecture and triggering the generalized seizure. The results add to the ultimate aim to construct a complete picture of brain interactions preceding and accompanying absence seizures in rats.