Seizure localization in humans: the effect of inhibitory surround on the EEG

描述（由申请人提供）：该项目旨在实现脑电图解释的重大概念性进展，脑电图是癫痫诊断评估的基石，也是有效性依赖于靶向相关脑区的治疗的基础。使用EEG记录来识别癫痫发作期间活跃的皮质部位在很大程度上依赖于高振幅EEG波形反映同一部位处的强烈同步神经放电的假设。然而，体外研究的数据表明，在癫痫发作期间存在的极端病理条件下，两种局部神经元活动模式占主导地位：急剧的 以超同步爆发放电为标志的分界发作病灶，以及以大突触传导但最小的去突触化放电为特征的周围发作半影，归因于快速激活的前馈抑制性抑制。因此，半影区的神经活动不会主动传播癫痫发作，而是扮演“无辜旁观者”的角色。由于视觉范围内的EEG信号容易反映突触电导，但对神经活动不太敏感，因此临床上被鉴定为“癫痫发作区”并靶向切除或集中治疗的脑区域包括发作灶和半影。本提案的目标是确定半影扭曲EEG提供的癫痫脑区域视图的程度。我们将获得接受侵入性长期监测（作为耐药性癫痫手术治疗的一部分）的患者癫痫发作的靶向微电极阵列记录，以评估发作病灶和半影区神经元活动对EEG的贡献。焦点/半影椎间盘切开术还为高频振荡（HFO）的作用提供了明确的机制解释，这是由于高伽马活性和多单位放电之间的众所周知的关系。通过使用神经放电数据来建立针对癫痫发作病灶的发作HFO的标准，我们将创建一种有用的方法来识别由临床电极采样的整个区域中的发作病灶的时间和空间轨迹。我们希望这些研究将导致一个新的临床方法发作脑电图解释。这将是一个根本性的进步，将影响所有针对癫痫发作的癫痫治疗。

DESCRIPTION (provided by applicant): This project aims to achieve a major conceptual advance in the interpretation of EEG, the cornerstone of epilepsy diagnostic evaluation and the basis for therapies whose effectiveness relies on targeting relevant brain areas. The use of EEG recordings to identify cortical sites that are active during a seizure relies heavily on the assumption that high amplitude EEG waveforms reflect intense, synchronous neural firing at the same site. Data from in vitro studies, however, suggest that during the extreme pathological conditions that exist during a seizure, two regional neuronal activity patterns dominate: a sharply demarcated ictal focus marked by hypersynchronous burst firing, and a surrounding ictal penumbra characterized by large synaptic conductances but minimal, desynchronized firing, attributed to a rapidly activated feedforward inhibitory restraint. Thus, neural activity in the penumbra does not actively propagate the seizure, but rather takes the role of an "innocent bystander". Because EEG signals in the visual range readily reflect synaptic conductances but are less sensitive to neural activity, brain regions clinically identified as the "seizure onset zoe" and targeted for resection or focused treatment include both the ictal focus and penumbra. The goal of this proposal is to establish the degree to which the penumbra distorts the view of epileptic brain regions provided by EEG. We will obtain targeted microelectrode array recordings of seizures in patients undergoing invasive long term monitoring as part of surgical treatment for pharmacoresistant epilepsy, to assess the contribution to EEG of neuronal activity both in the ictal focus and in penumbral regions. The focus/penumbra dischotomy also provides a clear, mechanistic explanation for the role of high frequency oscillations (HFOs), due to the well- known relationship between high gamma activity and multiunit firing. By using the neural firing data to establish criteria for ictal HFOs that are specific for the seizure focus, we will ceate a useful method of identifying the temporal and spatial trajectory of the ictal focus across the entire region sampled by clinical electrodes. We expect that these studies will lead to a new clinical methodology for ictal EEG interpretation. This would be a fundamental advance that will affect all epilepsy treatments targeting seizures where they arise.