Microscale Electrophysiology of Epileptic Cortex - Resubmission - 1

项目摘要 癫痫和癫痫发作的外科治疗包括记录癫痫发作活动以确定癫痫发作区 (SOZ)尽可能多地切除SOZ。现有的方法，如皮质电图 （ECoG），定义癫痫皮质-脑组织与潜在的启动癫痫发作-但不准确， 40-60%的患者在切除/消融术后没有实现持久的癫痫发作自由。这种结果差距 激发了人们对识别新的神经生理学生物标志物的兴趣，以识别用于神经外科手术的脑区域。 最大限度地发挥癫痫手术的益处。就像癫痫的宏观组织 大脑是异质的，具有相互连接的大脑区域，这些区域有助于癫痫发作的开始和扩散， 致痫皮质的微尺度组织也是异质性的，包含亚毫米区域， 在癫痫发作之间产生微尺度的发作间期活动。微尺度事件可能有助于产生 在标准宏观尺度下观察到临床癫痫发作，但尚未进行研究，因为在 标准临床皮层脑电图记录研究微尺度事件需要微尺度ECoG记录。下 其他支持，我们已经开发出一种新的电极阵列，提供高密度的微接触记录， 大皮层区域的微尺度事件，101 cm 2。电极记录皮层表面电位， 分辨率和覆盖范围的任何目前临床上可用的技术。 对于这个R21提案，我们建议发起临床医生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特性。我们建议调查的机制和 癫痫样活动的临床意义我们将重点讨论微尺度模型的两个预测。 目的1测试了发作间期微癫痫发作与发作期癫痫发作具有相似细胞机制的机制预测 癫痫发作事件目的2通过检查微尺度记录的关系来测试微尺度记录的临床意义。 术中记录的癫痫发作发生在易受癫痫发作启动和早期传播影响的皮质， 标准临床记录接受诊断监测的患者的初步术中研究 证明了我们方法的可行性。因此，R21提案将确定具体的潜在价值， 机制和/或临床，研究微尺度发作间期事件。成果将系统推进 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.