Abstract
Growing evidence suggests that excitatory neurons in the brain play a significant role in seizure generation. Nonetheless, spiny stellate cells are cortical excitatory non-pyramidal neurons in the brain, whose basic role in seizure occurrence is not well understood. In the present research, we study the critical role of spiny stellate cells or the excitatory interneurons (EI), for the first time, in epileptic seizure generation using an extended neural mass model inspired by a thalamocortical model originally introduced by another research group. Applying bifurcation analysis on this modified model, we investigated the rich dynamics corresponding to the epileptic seizure onset and transition between interictal and ictal states caused by EI connectivity to other cell types. Our results indicate that the transition between interictal and ictal states (preictal signal) corresponds to a supercritical Hopf bifurcation, and thus, the extended model suggests that before seizure onset, the amplitude and frequency of neural activities gradually increase. Moreover, we showed that (1) the altered function of GABAergic and glutamatergic receptors of EI can cause seizure, and (2) the pathway between the thalamic relay nucleus and EI facilitates the transition from interictal to ictal activity by decreasing the preictal period. Thereafter, we considered both sensory and cortical periodic inputs to study model responses to various harmonic stimulations. Bifurcation analysis of the model, in this case, suggests that the initial state of the model might be the main cause for the transition between interictal and ictal states as the stimulus frequency changes. The extended thalamocortical model shows also that the amplitude jump phenomenon and non-linear resonance behavior result from the preictal state of the modified model. These results can be considered as a step forward to a deeper understanding of the mechanisms underlying the transition from normal activities to epileptic activities.
Highlights
Epilepsy is one of the most common disorders of the central nervous system (CNS), which causes sudden abnormal and synchronized brain activities, resulting in seizures
Experimental studies have shown that changes in the function of GABAergic and glutamatergic receptors in the cortex of rats can be seen in genetic absence, tonic, and clonic seizure onset (Cortez et al, 2004; Jones et al, 2008; Errington et al, 2011)
Based on the paradoxical behavior of glutamatergic and GABAergic receptors discussed in sections “Transition Dynamics Produced by GABAergic Receptor-Mediated Inhibition in Excitatory Interneurons,” and ““Transition Dynamics Produced by Glutamatergic Receptor-Mediated Excitation in Excitatory Interneurons,” here, we explore the effect of decreased glutamatergic synaptic strength from the thalamus to the neocortex on seizure propagation using the extended model
Summary
Epilepsy is one of the most common disorders of the central nervous system (CNS), which causes sudden abnormal and synchronized brain activities, resulting in seizures. Spiny Stellate Cells in Epilepsy to have drug-resistant epilepsy, and treatments such as surgery or stimulation-based treatments like deep brain stimulation (DBS) can be considered for these kinds of drug-resistant patients (Shan et al, 2021). A seizure can be composed of four distinct states including preictal, ictal, interictal, and postictal. The preictal state appears before the seizure begins and indicates that seizures do not start out of nothing. The preictal signal can be used to predict seizure occurrence. Understanding the mechanism of generation of the preictal period opens the way for a more precise seizure prediction and thereby more reliable automatic interventions to prevent the seizure occurrence (Moghim and Corne, 2014)
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