Characterization and Modeling of Epileptic Spasm Propagation Dynamics

点击翻译按钮获取中文摘要

Epilepsy is one of the most frequently diagnosed neurologic conditions in childhood. Compared to adults, children have a relatively higher incidence of seizures, and notable differences in seizure etiology and consequence. In many cases, epileptic activity originates from malformed tissue within the developing brain, and when such tissue can be localized and surgically removed, it is possible to achieve subsequent seizure freedom. There is a particular urgency to perform these interventions in children, as persistent epileptic activity can have devastating consequences on cognitive development. Over the last two decades, the sponsors and collaborators of this proposal have published on research towards anatomically, metabolically, and electrophysiologically localizing seizure onset in epilepsy patients. However, relatively less is known about the exact spatiotemporal dynamics of epileptic propagation, which can make it difficult to appreciate clinical and research findings in the greater context of epileptic symptoms. The goal of this proposal is to help bridge this gap by identifying the pathways that epileptic activity takes as it propagates through the brain. This project will specifically investigate epileptic spasms: very brief seizures that occur in repetitive bursts and are most often seen in young patients. By decomposing the intracranial electroencephalography associated with these spasms, mapping electrode locations to diffusion-weighted imaging tractography, and studying activity that reveals the nature of this anatomy, we will trace the dynamics of spasm signals as they move through the brain and identify their alignment with known brain networks. Understanding the anatomical and functional networks that most constrain spasm propagation could improve the prediction of seizure onset zones; the entire spatiotemporal profile of the spasms could be fit to an individualized framework, and electrodes that show initial spasm activity at ambiguously similar times may be favored or disfavored as potential spasm origins based on subsequent activity. The efficacy of this information will be more practically assessed when integrated into seizure simulation models, which can retrospectively predict the functional outcome of surgeries based on their planned anatomical changes and the kinds of seizure propagation such changes would prohibit. By seeing this research through, the trainee will be exposed to the acute conditions and therapies related to his work as new patients present for surgery, as well as the longer-term implications of therapy efficacy and neurodevelopment as patients return for clinical follow up. He will help generate information relevant to current gold standard therapies, while simultaneously contributing to conceptions of the disease’s natural course and variability. Ultimately, he will learn the process, and witness the actionable outcomes, of addressing a research question in a clinical setting, and he will lay a strong foundation for his career as a physician-scientist.