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

描述（由申请人提供）：该提案的目标是通过在广泛的时空尺度上表征其电生理活动来定位人类癫痫网络。几十年来，临床颅内EEG（IEEG）使用有限的空间（厘米尺度）和时间（~0.5-100 Hz）带宽，更多地基于传统而不是现代神经科学，使癫痫学家在癫痫手术评估期间寻找离散的、可切除的“电描记病变”感到沮丧。类似地，在癫痫发作充分确定可以在标准临床宏电极上检测到之后，最近应用直接脑刺激来中止癫痫发作的努力到目前为止只取得了部分成功。我们假设，提高临床颅内EEG的空间和时间分辨率可以提高癫痫手术和响应性脑刺激控制癫痫发作的疗效。人类癫痫网络产生的病理活动范围从立方厘米的脑组织产生的癫痫发作和尖峰，到亚毫米尺度上发生的高频振荡。最近的证据表明，这些信号的重要组成部分是在标准临床IEEG检测不到的频率上发现的。使用同时IEEG记录从微丝阵列和临床宏电极，我们的小组已经开始表征两个潜在的特征癫痫脑，高频振荡和“微癫痫发作”，这是传统的临床IEEG的分辨率之外。在这个应用中，我们提出了分析连续的，高分辨率的，宽带宽的IEEG记录同时从微线阵列和临床宏电极，以本地化人类癫痫网络。我们将在一组接受癫痫手术评估的患者中前瞻性地将我们的发现与手术结果相关联。这项工作建立在我们在转化神经工程方面的既定努力之上，将最先进的癫痫护理与尖端研究相结合。人类癫痫脑的神经元网络是多尺度的;从以皮质柱（~300 - 600 <m）的尺度组织的细胞集合延伸到以叶结构组织的大尺度网络。这些病理性网络产生在宽范围的频率（0.01 - 1000 Hz）和空间尺度上的振荡，而临床EEG没有探测到。我们的实验室和其他实验室已经确定了发生在临床IEEG范围之外的病理性网络振荡，这些振荡似乎是致痫区的特征。

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.