Closed-loop Control Of Epileptiform Activity With Optogenetics

Epilepsy is one of the most common serious neurological disorders. Approximately, 50 million people worldwide have epilepsy, and nearly 90% of cases occur in low- and middle-income countries. Meanwhile, epilepsy is considered to be a chronic disease which lasts for several years, even decades of years. People with seizures tend to have negative influence on physical problems, as well as mental development. How to control the horrible seizures is the fundamental issues in epilepsy research, but unfortunately, there are no effective control methods. In this thesis, we combine computational neuron model with control theory and propose a closed-loop control strategy based on neuronal model, which achieve the closed-loop control of epilepsy.In our paper, we analyze the current situation and development of the research and control of epilepsy model, and then propose closed-loop control that use Wilson-Cowan model and optogenetic tool. First of all, we built Wilson-Cowan neural models, and study the characteristic of single column. We explore the influence of external stimulus without noise. Second, based on the single column model, we model two columns and n columns models. In this part, we discuss how the coupling strenghth affect the firing rate. The results show that when the firing rate exhibits oscillation with time variation, the neuron polulations is in seizures status. At the same time, when the firing rate stay steady, the neuron polulations is at resting state. Then we built a four-state optogenetic model of ChR2, and analyze the influence of irridance, voltage, and temperture. Finally, we combine the Wilson-Cowan model with optogenetic model, and consturct a Wilson-Cowan neural model based on optogenetic. Analyzing its non-linear dynamic characteristics, we compare the closed-loop control with open-loop control. The simulation shows that the closed-loop control can inhibit seizure waves more effective than the open-loop control.In this thesis, the closed-loop control strategy of neurons and neuron populations under the external optogenetic stimulation is proposed and the dynamic characteristics of the system are obtained through model analysis. The simulation results demonstrate that the effectiveness of the proposed scheme, and provide theoretical guidance for electrical stimulation therapy of neurologic diseases.