Spatiotemporal dynamics of epileptic activity

项目总结 癫痫是一种以自发性、反复发作为特征的神经系统疾病。然而，a 相当大的人群(~1/3)的局灶性癫痫患者对抗癫痫药物没有反应。此外， 替代的治疗策略(如电刺激或切除手术)取决于是否准确 癫痫发作起始区的定位，这在目前的技术下可能是困难的。这可能是因为贫穷。 临床记录方式的空间分辨率，例如脑电图法。为此，这个项目 旨在确定癫痫发作起始区内活动产生的独特标志物，从而阐明 耐药性局灶性癫痫发作再发的机制。从长远来看，结果是 这项研究产生的结果不仅会增加我们对癫痫病理的整体认识，而且还会 完善对耐药局灶性癫痫患者的个体化治疗。总体假设是， 发作起始区的棘波活动与宏观半影的局部场势相互作用 这种关系在人类局灶性癫痫中是独一无二的。为了实现这一目标并测试整体 假设，将追求以下目标：(1a)确定时空尖峰触发的平均值 通过同时考虑尖峰时间和位置来确定尖峰活动和LFP之间的关系。(1B)数学 将建立癫痫发作起始区内外的癫痫活动模型，以证实 结果。(2a)使用模板将发作期的棘波分类为兴奋性和抑制性群体- 凸壳变化的匹配和建模。(2B)研究兴奋性--的时空动力学 癫痫发作期间的抑制种群。这一分析的结果将产生一个强大的多尺度 在发作事件期间和周围的网络状态的表征。计算方法将会 将探索癫痫发作、传播和终止的具体机制。这个 这一提议的结果可能具有有助于确定癫痫发作的翻译含义 区域或开发新的治疗策略，如皮质内刺激方法。 这项拟议的研究将在协作和跨学科的环境中进行， 培训潜力，因为它包括导师机会、合作机会、出版物机会、 勇往直前，善于沟通。具体地说，这项研究将在 芝加哥大学计算癫痫研究方面的专家。这一培训经验还将提供 有机会在科学研究、癫痫病理学、计算建模、理论研究方面积累专业知识 神经科学、非线性动力学和数据分析。

PROJECT SUMMARY Epilepsy is a neurological disorder that is characterized by spontaneous, recurrent seizures. However, a significant population (~1/3rd) of focal epilepsy patients does not respond to anti-epileptic drugs. Furthermore, alternative treatment strategies (such as electrical stimulation or resective surgery) depend on accurate localization of the seizure onset zone, which can be difficult with current technology. This may be due to poor spatial resolution of clinical recording modalities, such as electroencephalography. To this end, this project seeks to identify unique markers that arise from activity within the seizure onset zone and thus, elucidate the mechanisms responsible for seizure recruitment in drug-resistant focal epilepsy. In the long term, the results generated by this research will not only increase our overall understanding of epilepsy pathology, but also refine individualized therapies for drug-resistant focal epilepsy patients. The overall hypothesis is that the spiking activity from the seizure onset zone interacts with the local field potential of the macroscopic penumbra and that this relationship is unique in human focal epilepsy. To fulfill this objective and test the overall hypothesis, the following aims will be pursued: (1A) Determine the spatiotemporal spike-triggered average between spiking activity and the LFP by accounting for both spike timing and location. (1B) A mathematical model of seizure activity within and outside of the seizure onset zone will be developed to corroborate the results. (2A) Sort spikes from the ictal epoch into excitatory and inhibitory populations using template- matching and modeling of convex hull changes. (2B) Investigate the spatiotemporal dynamics of excitatory- inhibitory populations during a seizure. The results from this analysis will yield a powerful multi-scale characterization of network states during and around seizure events. The computational approaches that will be utilized will probe specific mechanisms that underlie seizure onset, propagation, and termination. The outcomes of this proposal may have translational implications that facilitate identification of the seizure onset zone or the development of novel therapeutic strategies, such as intracortical stimulation approaches. This proposed research will be conducted in a collaborative and interdisciplinary environment with significant training potential as it includes growth in opportunities for mentorship, collaborations, publications, grantsmanship, and communication. Specifically, this research will be conducted under the mentorship of experts at the University of Chicago in computational epilepsy work. This training experience will also provide opportunities to build expertise in scientific inquiry, epilepsy pathology, computational modeling, theoretical neuroscience, nonlinear dynamics, and data analysis.