Microseizures, Ultra-slow & High Frequency Oscillations: Biomarkers of epilepsy

描述（由申请人提供）：本提案的目标是通过在广泛的时空尺度上表征人类癫痫网络的电生理活动来定位人类癫痫网络。几十年来，临床颅内脑电图（IEEG）使用有限的空间（厘米尺度）和时间（~0.5-100 Hz）带宽，更多地基于传统神经科学而不是现代神经科学，这让癫痫学家在癫痫手术评估中寻找离散的、可切除的“电图病变”感到沮丧。类似地，最近的尝试是，在癫痫发作充分确立，可以在标准的临床大电极上检测到之后，应用直接脑刺激来中止癫痫发作，但到目前为止，只取得了部分成功。我们假设提高临床颅内脑电图的时空分辨率可以提高癫痫手术和脑刺激控制癫痫发作的效果。人类癫痫网络产生的病理活动范围从由立方厘米脑组织产生的癫痫发作和尖峰，到发生在亚毫米尺度上的高频振荡。最近的证据表明，这些信号的重要组成部分是在标准临床脑电图检测不到的频率上发现的。通过同时使用来自微线阵列和临床大电极的脑电图记录，我们的团队已经开始描述两种潜在的癫痫性大脑特征，高频振荡和“微癫痫”，这是传统临床脑电图的分辨率之外的。在这个应用中，我们建议分析从微线阵列和临床大电极同时记录的连续、高分辨率、宽带宽的脑电图，以定位人类癫痫网络。我们将把我们的发现与手术结果联系起来，前瞻性地，在一组接受癫痫手术评估的患者中。这项工作建立在我们在转化神经工程方面的既定努力的基础上，融合了最先进的癫痫护理和前沿研究。人类癫痫大脑的神经网络是多尺度的从在皮层柱（~300 - 600 <m）上组织的细胞集合扩展到在叶状结构上组织的大规模网络。这些病理网络产生的振荡频率范围很广（0.01 - 1000赫兹），而且是临床脑电图无法探测到的空间尺度。我们的实验室和其他实验室已经确定了发生在临床IEEG范围之外的病理网络振荡，这似乎是癫痫区的特征。

DESCRIPTION (provided by applicant): The goal of this proposal is to localize human epileptic networks by characterizing their electrophysiological activity over a wide range of spatiotemporal scales. Decades of clinical intracranial EEG (IEEG) using restricted spatial (centimeter scale) and temporal (~0.5-100 Hz) bandwidth, based more on tradition than modern neuroscience, have frustrated epileptologists looking for discrete, resectable "electrographic lesions" during evaluation for epilepsy surgery. Similarly, recent efforts to apply direct brain stimulation to abort seizures after they are sufficiently established to be detected on standard clinical macroelectrodes have, so far, met with only partial success. We hypothesize that enhancing the spatial and temporal resolution of clinical intracranial EEG can improve the efficacy of epilepsy surgery and responsive brain stimulation to control seizures. Human epileptic networks produce pathological activity that ranges from seizures and spikes, generated by cubic centimeters of brain tissue, to high frequency oscillations that occur on sub-millimeter dimensions. Recent evidence suggests that important components of these signals are found at frequencies not detected by standard clinical IEEG. Using simultaneous IEEG recordings from microwire arrays and clinical macroelectrodes, our group has begun to characterize two potential signatures of epileptogenic brain, high frequency oscillations and "micro-seizures," that are outside the resolution of conventional clinical IEEG. In this application, we propose analysis of continuous, high-resolution, wide- bandwidth IEEG recorded simultaneously from microwire arrays and clinical macroelectrodes in order to localize human epileptic networks. We will correlate our findings with surgical outcome, prospectively, in a cohort of patients undergoing evaluation for epilepsy surgery. This work builds upon our established effort in Translational Neuroengineering melding state of the art epilepsy care with cutting-edge research. PUBLIC HEALTH RELEVANCE The neuronal networks of human epileptic brain are multiscale; extending from cellular assemblies organized on the scale of cortical columns (~300 - 600 <m) to large-scale networks organized over lobar structures. These pathological networks generate oscillations over a wide range of frequency (0.01 - 1000 Hz) and spatial scales not probed by clinical EEG. Our laboratory and others have identified pathological network oscillations occurring outside the range of clinical IEEG that appear to be signatures of the epileptogenic zone.