Characterization and Modeling of Epileptic Spasm Propagation Dynamics

癫痫是儿童时期最常见的神经系统疾病之一。与成年人相比， 儿童癫痫发作的发生率相对较高，癫痫发作的病因和 后果在许多情况下，癫痫活动起源于发育中的大脑中的畸形组织， 当这种组织可以被定位并通过外科手术切除时，就有可能实现随后的无癫痫发作。 对儿童进行这些干预措施尤其紧迫，因为持续的癫痫活动可能会导致 对认知发展造成毁灭性的后果。在过去的二十年里，赞助商和合作者 的这一建议已发表的研究，对解剖学，代谢，和电生理学 定位癫痫患者的癫痫发作。然而，相对较少的是知道确切的时空 癫痫传播的动力学，这可能使人们难以理解临床和研究结果， 癫痫症状的大背景。本提案的目标是通过确定 癫痫活动在大脑中传播的途径。 这个项目将专门研究癫痫痉挛：非常短暂的癫痫发作，发生在重复爆发 最常见于年轻患者。通过分解颅内脑电图 通过这些痉挛，将电极位置映射到弥散加权成像纤维束成像，并研究活动 揭示了这种解剖学的本质，我们将追踪痉挛信号在肌肉中移动时的动力学。 并确定它们与已知大脑网络的对齐。了解解剖和功能 最能限制痉挛传播的网络可以改善对癫痫发作区域的预测; 痉挛的时空轮廓可以适合于个体化的框架，并且显示初始痉挛的电极可以被配置为： 在模糊相似的时间的痉挛活动可能是有利的或不利的，作为潜在的痉挛起源， 后续活动。这些信息的有效性将在整合到 癫痫发作模拟模型，可以回顾性地预测手术的功能结果， 有计划的解剖学变化和这种变化将禁止的癫痫传播类型。 通过这项研究，受训者将接触到急性疾病和相关治疗。 他的工作作为新的病人目前的手术，以及长期的影响，治疗效果和 神经发育作为患者返回临床随访。他将帮助生成与当前 金标准疗法，同时有助于疾病的自然过程的概念， 可变性最终，他将学习解决研究问题的过程，并见证可操作的结果。 问题在临床环境中，他将奠定了坚实的基础，他的职业生涯作为一个医生，科学家。

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.