A Unifying Explanation of Primary Generalized Seizures Through Nonlinear Brain Modeling and Bifurcation Analysis

Abstract

The aim of this paper is to explain critical features of the human primary generalized epilepsies by investigating the dynamical bifurcations of a nonlinear model of the brain's mean field dynamics. The model treats the cortex as a medium for the propagation of waves of electrical activity, incorporating key physiological processes such as propagation delays, membrane physiology, and corticothalamic feedback. Previous analyses have demonstrated its descriptive validity in a wide range of healthy states and yielded specific predictions with regards to seizure phenomena. We show that mapping the structure of the nonlinear bifurcation set predicts a number of crucial dynamic processes, including the onset of periodic and chaotic dynamics as well as multistability. Quantitative study of electrophysiological data supports the validity of these predictions. Hence, we argue that the core electrophysiological and cognitive differences between tonic-clonic and absence seizures are predicted and interrelated by the global bifurcation diagram of the model's dynamics. The present study is the first to present a unifying explanation of these generalized seizures using the bifurcation analysis of a dynamical model of the brain.

Control of absence seizures induced by the pathways connected to SRN in corticothalamic system

“…Projection between the cortex and thalamus neurons has been shown as an important factor for inducing seizures (Breakspear et al 2006;Marten et al 2009;Paz et al 2011). For example, Breakspear et al studied general seizure phenomena induced by m se in a corticothalamic network (Breakspear et al 2006).…”

“…Projection between the cortex and thalamus neurons has been shown as an important factor for inducing seizures (Breakspear et al 2006;Marten et al 2009;Paz et al 2011). For example, Breakspear et al studied general seizure phenomena induced by m se in a corticothalamic network (Breakspear et al 2006). Extending existing results, we will investigate the absence seizure activities induced by the projection from excitatory pyramidal population to SRN (i.e., m se ), and how the pathways in the basal ganglia (i.e., SNr-SRN and SNr-TRN) to control these seizure activities.…”

“…Unless otherwise noted, we use the parameter values as listed in Appendix for numerical simulations. These values result from physiological experiments, and can be found in previous studies (Breakspear et al 2006;Chen et al 2014;Robinson et al 1998Robinson et al , 2001Robinson et al , 2003. At the same time, some parameter values are slightly adjusted to generate stable SWDs oscillation in corticothalamic circuit.…”

“…And when the activation level of the SNr increases, the inhibitory effect on SRN by the direct pathway SNr-SRN also increases, but the inhibitory effect on SRN by the indirect pathway SNr-TRN-SRN decreases. Finally, the inhibitory effect by the Seizure activities induced by the excitatory input from SRN to TRN Until now, it is shown that there are three main arguments about origin of the epileptic seizures: (1) SWDs generated in cortex neurons; (2) SWDs generated in thalamus neurons; (3) SWDs appeared in cortex neurons, and it transforms from a ''spindles'' wave generated in thalamus neurons (Breakspear et al 2006). Hence, the thalamus neurons can play a vital role in the generation of epileptic seizures (Breakspear et al 2006;Deransart et al 1998;Paz et al 2007).…”

“…In addition, the absence seizures can originate from the mutual roles between the cerebral cortex and the thalamus, which form the corticothalamic circuits. This can be witnessed by a number of clinical researches and computational modeling studies (Breakspear et al 2006;Coenen and van Luijtelaar 2003;Marten et al 2009;Robinson et al 2002;Timofeev and Steriade 2004). For example, Roberts and Robinson (2008) used a physiologically based continuum model (i.e., the mean-field model) of the corticothalamic system to explain the basic mechanisms of the seizure activity.…”