Microscale Electrophysiology of Epileptic Cortex - Resubmission - 1

项目摘要 癫痫和癫痫的外科治疗包括记录癫痫发作活动以确定癫痫发作的起始区 (SOZ)，并尽可能多地切除SOZ。现有的方法，如皮层脑电图术 (ECOG)，定义致痫皮质-具有引发癫痫发作的潜力的脑组织-但不准确为 40-60%的患者在切除/消融后不能获得持久的癫痫缓解。这一结果差距已经 激发了人们对识别新的神经生理生物标记物的兴趣，以确定神经外科的大脑区域 干预以最大限度地提高癫痫手术的效益。就像癫痫患者的宏观组织 大脑是异质性的，有相互连接的大脑区域，这些区域有助于癫痫的启动和传播， 致痫皮质的微尺度组织也是异质性的，包含亚毫米级的区域，可以 在两次发作之间产生微小的发作间歇性活动。微尺度事件可能有助于产生 在标准宏观尺度下观察到的临床癫痫发作，但尚未进行调查，因为它们在 标准的临床ECoG记录。研究微尺度事件需要微尺度的µECoG记录。在……下面 其他支持，我们开发了一种新的电极阵列，它提供高密度微接触记录 大脑皮层区域上的微尺度事件，1平方厘米。电极记录的皮层表面电位超过了 任何目前可用于临床的技术的分辨率和覆盖面。 对于这个R21提案，我们建议启动临床医生和神经科学家-工程师之间的协作 开发和测试癫痫发作网络的多尺度特性。我们建议研究这一机制和 微尺度癫痫样活动的临床意义。我们将重点关注微尺度模型的两个预测。 目的1验证发作间期微电发作与发作期相似的细胞机制的机制预测 癫痫发作事件。目的2检验微尺度记录的临床意义，探讨微尺度记录与微尺度记录的关系。 术中记录到皮层的癫痫易受癫痫发作的启动和早期传播的影响 标准的临床记录。接受诊断性监测的患者的初步术中研究 论证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， 研究微尺度发作间歇期事件的机制和/或临床。结果将系统性地推进 更广泛地研究致痫组织的微尺度电生理学。

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.