Spatiotemporal dynamics of epileptic activity

癫痫活动的时空动态

• 批准号: 10599685
• 负责人: Sarita Srisai Deshpande
• 金额: $ 3.68万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10599685
• 关键词: Accounting; Adult; Antiepileptic Agents; Chicago; Clinical; Collaborations; Communication; Computer Models; Data Analyses; Data Set; Development; Diagnosis; Drug resistance; Electric Stimulation; Electrocorticogram; Electrodes; Electroencephalography; Epilepsy; Event; Evolution; Failure; Frequencies; Grant; Growth; Human; Interneurons; Knowledge; Lead; Location; Magnetic Resonance Imaging; Measures; Mentorship; Methodology; Methods; Microelectrodes; Mission; Modality; Modeling; Neocortex; Neurons; Neurosciences; Nonlinear Dynamics; Operative Surgical Procedures; Outcome; Partial Epilepsies; Pathology; Patients; Population; Property; Public Health; Publications; Recurrence; Research; Resolution; Role; Scientific Inquiry; Seizures; Sorting; Technology; Testing; Theoretical model; Training; United States National Institutes of Health; Universities; Work; alternative treatment; collaborative environment; comparative; epileptiform; experience; hippocampal pyramidal neuron; imaging modality; individualized medicine; innovation; mathematical model; neocortical; nervous system disorder; novel; novel therapeutic intervention; recruit; spatiotemporal; surgery outcome; treatment strategy

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.

项目摘要 癫痫是一种神经系统疾病，其特征是自发的，复发性癫痫发作。但是， 局灶性癫痫患者的大量人群（〜1/3）对抗癫痫药不反应。此外， 替代治疗策略（例如电刺激或改善手术）取决于准确 癫痫发作区域的定位，当前技术可能很困难。这可能是由于差 临床记录方式的空间分辨率，例如脑电图。为此，这个项目 试图确定由癫痫发作区域内活动产生的独特标记，从而阐明 导致耐药性局灶性癫痫发作的机制。从长远来看，结果 这项研究产生的不仅会增加我们对癫痫病理学的整体理解，而且还会增加 为抗药性局灶性癫痫患者提供了个性化疗法。总体假设是 癫痫发作区的尖峰活动与宏观半阴茎的局部场电位相互作用 这种关系在人类局灶性癫痫中是独一无二的。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 通过考虑尖峰时序和位置，在尖峰活动和LFP之间。 （1b）数学 将开发癫痫发作区域内外的癫痫发作活动模型，以证实 结果。 （2a）使用模板将发作时期的尖峰从发作时期分类为兴奋性和抑制种群 凸船体的匹配和建模变化。 （2b）研究兴奋性的时空动力学 癫痫发作期间的抑制种群。该分析的结果将产生强大的多尺度 在癫痫发作事件期间和周围的网络状态表征。计算方法将 使用将探测癫痫发作，繁殖和终止的特定机制。这 该提案的结果可能具有转化的含义，有助于鉴定癫痫发作 区域或新型治疗策略的发展，例如皮质内刺激方法。 这项拟议的研究将在协作和跨学科的环境中进行， 培训潜力包括增长指导，合作，出版物， 赠款和沟通。具体而言，这项研究将在 芝加哥大学计算癫痫工作的专家。这种培训经验也将提供 建立科学探究，癫痫病理学，计算建模，理论上的专业知识的机会 神经科学，非线性动力学和数据分析。