title: Mechanisms of seizure propagation in 2-dimensional centre-surround recurrent networks.
abstract: Understanding how seizures spread throughout the brain is an important problem in the treatment of epilepsy, especially for implantable devices that aim to avert focal seizures before they spread to, and overwhelm, the rest of the brain. This paper presents an analysis of the speed of propagation in a computational model of seizure-like activity in a 2-dimensional recurrent network of integrate-and-fire neurons containing both excitatory and inhibitory populations and having a difference of Gaussians connectivity structure, an approximation to that observed in cerebral cortex. In the same computational model network, alternative mechanisms are explored in order to simulate the range of seizure-like activity propagation speeds (0.1-100 mm/s) observed in two animal-slice-based models of epilepsy: (1) low extracellular [Formula: see text], which creates excess excitation and (2) introduction of gamma-aminobutyric acid (GABA) antagonists, which reduce inhibition. Moreover, two alternative connection topologies are considered: excitation broader than inhibition, and inhibition broader than excitation. It was found that the empirically observed range of propagation velocities can be obtained for both connection topologies. For the case of the GABA antagonist model simulation, consistent with other studies, it was found that there is an effective threshold in the degree of inhibition below which waves begin to propagate. For the case of the low extracellular [Formula: see text] model simulation, it was found that activity-dependent reductions in inhibition provide a potential explanation for the emergence of slowly propagating waves. This was simulated as a depression of inhibitory synapses, but it may also be achieved by other mechanisms. This work provides a localised network understanding of the propagation of seizures in 2-dimensional centre-surround networks that can be tested empirically.
authors: Victoria Research Labs, National ICT Australia, Parkville, Victoria, Australia.
authors: David
authors: D
authors: Hall
authors: Levin
authors: L
authors: Kuhlmann
mesh_terms: D000465:Algorithms; D001921:Brain / Q000503:physiopathology*; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology; D005110:Extracellular Space / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D008274:Magnesium
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