Improving models for control of seizures and spreading depression

Epileptic seizures and spreading depression are both pathological conditions characterized by abnormal, excessive discharge of population neuronal activities, accompanied by massive perturbation of ion homeostasis. My research goal is to understand the underlying mechanisms of these pathological dynamics in the brain, with the purpose of developing a novel model-based control approach to suppress pathological conditions.;To better understand the underlying mechanism of seizures and spreading depression, we first need to build computational models. I investigated how oxygen is involved with seizure generation, as well as how it interacts with ion dynamics such as potassium and sodium, with a computational model including dynamics of potassium, sodium and oxygen concentrations. The model was validated by real experimental data. I then extended this model to include the dynamics of chloride and volume for spreading depression - essential to characterize the fluxes and concentration changes. At the same time, I also found that there is a dynamical unification between seizures and SD. I have shown that these models can be used in model-based control frameworks to track experimentally inaccessible variables and parameters from recorded experimental data. This not only helps us understand the underlying mechanism of pathological conditions, but also provides a better foundation for model-based control of seizures and spreading depression. Lastly, I investigated the parameters of electrical stimulation in the hippocampus on freely moving rats. In preliminary control work in whole animals, I found that there were frequencies of controllers that were associated with cognitive side effects, and that these could be avoided by constraining such controllers to avoid such frequency ranges. Therefore, therapeutic stimulation will always be a balance between optimizing pathological dynamics control and the minimization of cognitive side effects.;This thesis not only sheds new light on the interrelation between seizures spreading depression, ion dynamics, and energy metabolism, but also provides a promising future for preventing and suppressing neurological diseases.