Unified Analysis of Global and Focal Aspects of Absence Epilepsy via Neural Field Theory of the Corticothalamic System

Abstract

A physiology-based corticothalamic model is investigated with focal spatial heterogeneity, to unify global and focal aspects of absence epilepsy. Numerical and analytical calculations are employed to investigate the emergent spatiotemporal dynamics induced by focal activity as well as their underlying dynamical mechanisms. The spatiotemporal dynamics can be categorized into three scenarios: suppression, localization, and generalization of the focal activity, as summarized from a phase diagram vs. focal width and characteristic axon range. The corresponding temporal frequencies and spatial extents of wave activity during seizure generalization and localization agree well with experimental observations of global and focal aspects of absence epilepsy, respectively. The emergent seizure localization provide a biophysical explanation of the temporally higher frequency but spatially more localized cortical waves observed in genetic rat models that display characteristics of human absence epilepsy. Predictions are also presented for further experimental test.\n\nAuthor SummaryAbsence epilepsy is characterized by a sudden paroxysmal loss of consciousness accompanied by oscillatory activity propagating over many brain areas. Although primary generalized absence seizures are supported by the global corticothalamic system, converging experimental evidence supports a focal theory of absence epilepsy. Here we propose a dynamical mechanism to unify the global and focal aspects of absence epilepsy, with focal absence seizures associated with seizure localization, and the global ones associated with seizure generalization. Our corticothalamic model is used to investigate how seizure rhythms and spatial extents are related in these two different aspects of absence epilepsy. The results account for the difference of the experimentally observed seizure rhythms and spatial extents between humans and genetic rat models, which has previously been used to argue against the validity of such rats as animal models of absence epilepsy in humans.