Abstract
A mesoscale network model is proposed for the development of spike and wave discharges (SWDs) in the cortico-thalamo-cortical (C-T-C) circuit. It is based on experimental findings in two genetic models of childhood absence epilepsy–rats of WAG/Rij and GAERS strains. The model is organized hierarchically into two levels (brain structures and individual neurons) and composed of compartments for representation of somatosensory cortex, reticular and ventroposteriomedial thalamic nuclei. The cortex and the two thalamic compartments contain excitatory and inhibitory connections between four populations of neurons. Two connected subnetworks both including relevant parts of a C-T-C network responsible for SWD generation are modelled: a smaller subnetwork for the focal area in which the SWD generation can take place, and a larger subnetwork for surrounding areas which can be only passively involved into SWDs, but which is mostly responsible for normal brain activity. This assumption allows modeling of both normal and SWD activity as a dynamical system (no noise is necessary), providing reproducibility of results and allowing future analysis by means of theory of dynamical system theories. The model is able to reproduce most time-frequency changes in EEG activity accompanying the transition from normal to epileptiform activity and back. Three different mechanisms of SWD initiation reported previously in experimental studies were successfully reproduced in the model. The model incorporates also a separate mechanism for the maintenance of SWDs based on coupling analysis from experimental data. Finally, the model reproduces the possibility to stop ongoing SWDs with high frequency electrical stimulation, as described in the literature.
Highlights
Absence epilepsy is characterized by recurring paroxysmal seizures with a diminishment of responsiveness and awareness with sudden onset and termination
For more detailed studies towards the mechanisms of spike-wave discharge (SWD) generation, various animal models have been used; most well known are two genetic absence models, rats of the WAG/Rij strain [2] and Genetic Absence Epileptic Rats form Strasbourg (GAERS) [3]. These models, first discovered in the eighties of the previous century, are well documented and validated as models for childhood absence epilepsy. They show the for absence epilepsy characteristic clinical concomitants accompanying the SWDs, such as mild facial myoclonus, accelerated breathing, and twitching of the vibrissae [4], as well as many other characteristics contributing to face, predictive and construct validity [2]
The number of model nodes in it is NPsY 1⁄4 160; NIsN 1⁄4 40; n. trigeminus (NT) C 1⁄4 80; NRs E 1⁄4 80. These surrounding areas correspond to other thalamic nuclei for TC and RE nodes, and for cortical areas connected to somatosensory cortex for PY and IN nodes, including frontal and occipital cortex, which are normally involved in SWDs [3, 46]
Summary
Absence epilepsy is characterized by recurring paroxysmal seizures with a diminishment of responsiveness and awareness with sudden onset and termination. For more detailed studies towards the mechanisms of SWD generation, various animal models have been used; most well known are two genetic absence models, rats of the WAG/Rij strain [2] and Genetic Absence Epileptic Rats form Strasbourg (GAERS) [3]. These models, first discovered in the eighties of the previous century, are well documented and validated as models for childhood absence epilepsy. They show the for absence epilepsy characteristic clinical concomitants accompanying the SWDs, such as mild facial myoclonus, accelerated breathing, and twitching of the vibrissae [4], as well as many other characteristics contributing to face, predictive and construct validity [2]
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