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， 儿童癫痫的发生率相对较高，在癫痫病因和 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，并且 当这种组织可以被定位并通过手术移除时，就有可能实现随后的癫痫自由。 尤其迫切需要在儿童中实施这些干预措施，因为持续性癫痫活动可能会 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 已经发表了关于解剖学、新陈代谢和电生理学的研究 癫痫患者癫痫发作的定位。然而，人们对确切的时空分布知之甚少。 癫痫传播的动力学，这可能使人们难以欣赏临床和研究结果。 癫痫症状的更大背景。这项提案的目标是通过确定 癫痫活动通过大脑传播时所采取的路径。 这个项目将专门研究癫痫痉挛：反复发作的非常短暂的癫痫发作。 最常见于年轻患者。通过分解相关的颅内脑电 有了这些痉挛，将电极位置标测到扩散加权成像纤维束成像，并研究活动 这揭示了这种解剖学的本质，我们将追踪痉挛信号在 并确定它们与已知的大脑网络的一致性。了解人体的解剖和功能 最限制痉挛传播的网络可以改善癫痫发作起始区的预测；整个 痉挛的时空分布可以符合个性化的框架，电极显示最初的 在模糊相似的时间内的痉挛活动可能被认为是潜在的痉挛起源，基于 后续活动。这一信息的效力将在结合到 癫痫模拟模型，它可以根据其功能结果回溯地预测手术的功能结果 有计划的解剖变化以及这种变化将禁止的癫痫发作传播的种类。 通过完成这项研究，学员将接触到与之相关的急性疾病和治疗 作为新的手术患者，他的工作，以及治疗效果和 随着患者返回进行临床随访，神经发育。他将帮助生成与当前 黄金标准疗法，同时有助于疾病的自然病程和 可变性。最终，他将学习解决一项研究的过程，并见证可操作的结果 在临床环境中提出问题，他将为他作为内科科学家的职业生涯奠定坚实的基础。

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.