Outgrowing Neurological Diseases: Microcircuits, Conduction Delay and Childhood Absence Epilepsy

Abstract

The study of familial disorders characterized by recurring changes in neurodynamics, such as epileptic seizures, paralysis and headaches, provide opportunities to identify the mechanisms for dynamic changes in the nervous system. Many of these diseases are channelopathies. The computational challenge is to understand how a constantly present molecular defect in an ion channel can give rise to paroxysmal changes in neurodynamics. The most common of these channelopathies is childhood absence epilepsy (CAE). Here we review the dynamical properties of three neural microcircuits thought to be important in epilepsy: counter inhibition, recurrent inhibition and recurrent excitation. Time delays, τ , are an intrinsic property of these microcircuits since the time for a signal to travel between two neurons depends on the distance between them and the axonal conduction velocity. It is shown that all of these microcircuits can generate multistability provided that τ is large enough. The term “multistability” means that there can be the co-existence of two or more attractors. Attention is drawn to the transient dynamics which can be associated with transitions between attractors, such as delay-induced transient oscillations. In this way we link the paroxysmal nature of seizure recurrences in CAE with time-delayed multistable dynamical systems. The tendency of children with CAE to outgrow their epilepsy is linked to developmental changes in axonal myelination which decrease τ .