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.

项目总结