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

描述(由申请者提供)：该项目旨在实现对脑电的解释方面的重大概念性进展，脑电是癫痫诊断评估的基石，也是治疗的基础，其有效性依赖于针对相关大脑区域的治疗。使用脑电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这样的假设，即高幅度脑电波形反映了同一部位强烈、同步的神经放电。然而，来自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，两种区域神经元活动模式占主导地位： 以超同步爆发式放电为标志的分界性发作灶，以及周围的发作半影区，其特征是大的突触电导，但最小的去同步放电，归因于快速激活的前馈抑制抑制。因此，半影区的神经活动并不是主动地传播癫痫发作，而是扮演一个“无辜的旁观者”的角色。由于视觉范围内的脑电信号容易反映突触传导，但对神经活动不那么敏感，因此临床上被确定为“癫痫发作ZOE”的大脑区域包括发作灶和半影区。这项建议的目标是确定半影区扭曲脑电提供的癫痫脑区域的程度。我们将获得有针对性的微电极阵列记录，作为耐药癫痫外科治疗的一部分，对接受侵入性长期监测的患者的癫痫发作进行记录，以评估发作灶和半影区神经元活动对脑电的贡献。焦点/半影视盘切开术也为高频振荡(HFO)的作用提供了一个明确的、机械的解释，这是因为众所周知，高伽马活动和多单位放电之间的关系。通过使用神经放电数据来建立针对癫痫灶的发作期HFO的标准，我们将获得一种有用的方法来识别临床电极采样的整个区域的发作期病灶的时间和空间轨迹。我们期望这些研究将为发作期脑电的解释带来一种新的临床方法。这将是一项根本性的进步，将影响所有针对癫痫发作的治疗。

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.