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

描述（由申请人提供）：本项目旨在实现脑电图解释的重大概念进步，这是癫痫诊断评估的基石，也是治疗的基础，其有效性依赖于靶向相关脑区。利用脑电图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脑电图波形反映同一部位强烈的、同步的神经放电的假设。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

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.