Microscale Electrophysiology of Epileptic Cortex - Resubmission - 1

癫痫皮层的微观电生理学 - 重新提交 - 1

• 批准号: 10527706
• 负责人: Daniel Friedman
• 金额: $ 25.05万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10527706
• 关键词: Ablation; Affect; American; Area; Biological Markers; Brain; Brain region; Clinical; Collaborations; Development; Devices; Diagnosis; Diagnostic; Diameter; Electrocorticogram; Electrodes; Electroencephalography; Electrophysiology (science); Engineering; Epilepsy; Event; Excision; Film; Freedom; Future; Generations; Heterogeneity; Implant; Intervention; Intractable Epilepsy; Investigation; Link; Measures; Microelectrodes; Modeling; Monitor; Morbidity - disease rate; Neocortex; Neurologic; Neurons; Operative Surgical Procedures; Outcome; Patients; Phase; Population; Property; Publishing; Records; Recurrence; Resected; Resolution; Seizures; Series; Signal Transduction; Site; Surface; Technology; Testing; Thinness; Tissues; Work; brain tissue; clinically significant; density; epileptiform; experimental study; improved; interest; liquid crystal polymer; meter; millimeter; mortality; neocortical; nervous system disorder; neurophysiology; neurosurgery; neurotechnology; nonhuman primate; novel; response; standard of care; surgery outcome; tumor

Project Summary Surgical treatment of epilepsy and seizures involves recording seizure activity to identify the seizure onset zone (SOZ), and resecting as much of the SOZ as possible. Existing approaches, such as electrocorticography (ECoG), define epileptogenic cortex – brain tissue with the potential to initiate seizures – but are inaccurate as 40-60% of patients do not achieve durable seizure freedom after resection/ablation. This outcome gap has spurred an interest in identifying novel neurophysiological biomarkers to identify brain regions for neurosurgical intervention to maximize the benefit of epilepsy surgery. Just as the macroscale organization of the epileptic brain is heterogenous with interconnected brain regions that contribute to seizure initiation and spread, the microscale organization of epileptogenic cortex is also heterogenous, containing sub-millimeter regions that can generate microscale inter-ictal activity between seizures. Microscale events may contribute to the generation of clinical seizures observed at standard macroscales but have not been investigated as they are not detectable in standard clinical ECoG recordings. Studying microscale events requires microscale µECoG recordings. Under other support, we have developed a novel electrode array that provides high-density microcontact recording of microscale events over large cortical areas, 1 cm2. The electrode records cortical surface potentials beyond the resolution and coverage of any currently clinically-available technology. For this R21 proposal, we propose to initiate a collaboration between a clinician and a neuroscientist-engineer to develop and test the multiscale properties of seizure networks. We propose to investigate the mechanistic and clinical implications of microscale epileptiform activity. We will focus on two predictions of the microscale model. Aim 1 tests the mechanistic prediction that inter-ictal µ-seizures share similar cellular mechanisms as ictal seizure events. Aim 2 tests the clinical significance of microscale recordings by examining the relationship of µ- seizures recording intra-operatively to cortex vulnerable to seizure initiation and early propagation identified in standard clinical recordings. Preliminary intraoperative studies in patients undergoing diagnostic monitoring demonstrates the feasibility of our approach. This R21 proposal will therefore identify the specific potential value, mechanistic and/or clinical, of studying microscale interictal events. The results will advance systematic investigations of the microscale electrophysiology of epileptogenic tissue more broadly.

项目摘要 癫痫和癫痫发作的手术治疗涉及记录癫痫活性以鉴定癫痫发作区 （SOZ），并尽可能多地求解SOZ。现有方法，例如电视学 （ECOG），定义癫痫病皮质 - 脑组织具有启动癫痫发作的可能性 - 但不准确 40-60％的患者在切除/消融后无法获得持久的癫痫发作自由。这个结果差距有 激发了人们对识别新型神经生理生物标志物的兴趣，以鉴定神经外科的大脑区域 干预以最大程度地提高癫痫手术的益处。就像癫痫病的宏观组织 大脑与互连的大脑区域是异质的，有助于癫痫发作和扩散， 癫痫病皮质的微观组织也是异质的，其中包含可以 在癫痫发作之间产生显微镜间歇性活性。微观事件可能有助于产生 在标准宏观上观察到的临床癫痫发作，但尚未研究，因为它们在 标准的临床ECOG记录。研究显微镜事件需要微观的记录。在下面 其他支持，我们开发了一个新型的电极阵列，可提供高密度的微接触记录 大型皮质区域上的微观事件，1cm2。电极记录皮层表面电位 任何当前临床上可用技术的分辨率和覆盖范围。 对于此R21提案，我们建议启动临床和神经科学家工程师之间的合作 开发和测试癫痫发作网络的多尺度属性。我们建议调查机理和 微观癫痫样活性的临床意义。我们将重点关注微观模型的两个预测。 AIM 1测试了机械预测，即间歇性µ-塞济具有与ICTAL相似的细胞机制 癫痫事件。 AIM 2通过检查µ-的关系来测试微观记录的临床意义。 在术中记录对皮质内的癫痫发作，易于癫痫发作倡议和早期传播。 标准临床记录。接受诊断监测的患者的术中初步研究 展示了我们方法的可行性。因此，该R21提案将确定特定的潜在价值， 机械和/或临床，研究显微镜间介绍事件。结果将推进系统性 对癫痫组织微观生理学的研究更广泛。