Dynamic Transitions of Epilepsy Waveforms Induced by Astrocyte Dysfunction and Electrical Stimulation.

Experimental studies have shown that astrocytes participate in epilepsy through inducing the release of glutamate. Meanwhile, considering the disinhibition circuit among inhibitory neuronal populations with different time scales and the feedforward inhibition connection from thalamic relay nucleus to cortical inhibitory neuronal population, here, we propose a modified thalamocortical field model to systematically investigate the mechanism of epilepsy. Firstly, our results show that rich firing activities can be induced by astrocyte dysfunction, including high or low saturated state, high- or low-frequency clonic, spike-wave discharge (SWD), and tonic. More importantly, with the enhancement of feedforward inhibition connection, SWD and tonic oscillations will disappear. In other words, all these pathological waveforms can be suppressed or eliminated. Then, we explore the control effects after different external stimulations applying to thalamic neuronal population. We find that single-pulse stimulation can not only suppress but also induce pathological firing patterns, such as SWD, tonic, and clonic oscillations. And we further verify that deep brain stimulation can control absence epilepsy by regulating the amplitude and pulse width of stimulation. In addition, based on our modified model, 3 : 2 coordinated reset stimulation strategies with different intensities are compared and a more effective and safer stimulation mode is proposed. Our conclusions are expected to give more theoretical insights into the treatment of epilepsy.

Control analysis of electrical stimulation for epilepsy waveforms in a thalamocortical network.

Physiological experiments and computational models both show that the thalamic reticular nucleus (RE) participates in inducing various firing patterns of cortex. Absence seizure, featured by 2-4 Hz spike-wave discharges (SWD) oscillation, is a high incidence of disease in children. Lots of electrophysiological experiments have verified the correlation between absence seizures and RE, however, the dynamical mechanisms are not well understood. Based on previous Taylor model, we firstly study the effects of external input and self-inhibition of RE on epilepsy transition. We show that increasing external input and self-inhibition of RE can lead the system from epileptic state to normal state, and vice versa. Next, we explore two stimulus strategies added in RE and various transition behaviors can be induced, such as high saturated state to clonic. Meanwhile, as the intensity of stimulation increasing, they can not only suppress the SWD, but also produce tonic-clonic oscillation. Finally, the control of DBS on single neuron cluster and two neuron clusters are compared and we find stimulating RE and TC simultaneously is a superior mode to stimulate anyone of RE or TC. It is hoped that the results we obtained will have an enlightenment on clinical treatment.