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

人类癫痫定位：抑制性周围环境对脑电图的影响

• 批准号: 8714087
• 负责人: Catherine A Schevon
• 金额: $ 58.01万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714087
• 关键词: Active Sites; Address; Affect; Animals; Area; Biological Markers; Brain; Brain region; Calculi; Clinical; Data; Data Set; Diagnostic; Effectiveness; Electrodes; Electroencephalography; Epilepsy; Evaluation; Event; Evolution; Excision; Focal Seizure; Frequencies; Goals; High Frequency Oscillation; Human; In Vitro; Interneurons; Language; Lead; Maps; Methodology; Methods; Microelectrodes; Modeling; Monitor; Motor; Nature; Neurons; Operative Surgical Procedures; Outcome; Partial Epilepsies; Patients; Pattern; Postoperative Period; Property; Publishing; Recurrence; Resected; Role; Sampling; Seizures; Signal Transduction; Site; Slice; Source; Synapses; Syndrome; Techniques; Testing; Visual; Work; base; improved; indexing; neocortical; neurophysiology; novel strategies; novel therapeutics; public health relevance; relating to nervous system; restraint

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.

描述（由申请人提供）：该项目旨在在脑电图的解释方面取得重大概念进展，脑电图是癫痫诊断评估的基石，也是其有效性依赖于针对相关大脑区域的治疗的基础。使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这样的假设：高振幅脑电图波形反映了同一部位强烈、同步的神经放电。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，两种区域神经元活动模式占主导地位： 以超同步突发放电为特征的划定的发作焦点，以及以突触电导大但不同步放电为特征的周围发作半影，归因于快速激活的前馈抑制抑制。因此，半影中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。由于视觉范围内的脑电图信号很容易反映突触电导，但对神经活动不太敏感，临床上确定为“癫痫发作区域”并进行切除或集中治疗的大脑区域包括发作灶和半暗带。该提案的目标是确定半影扭曲脑电图提供的癫痫大脑区域视图的程度。作为耐药性癫痫手术治疗的一部分，我们将获得接受侵入性长期监测的患者癫痫发作的目标微电极阵列记录，以评估发作灶和半暗区神经元活动对脑电图的贡献。由于高伽马活动和多单元发射之间众所周知的关系，焦点/半影二分法还为高频振荡（HFO）的作用提供了清晰的机械解释。通过使用神经放电数据建立针对癫痫病灶的发作性 HFO 的标准，我们将创建一种有用的方法来识别临床电极采样的整个区域的发作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图解释带来新的临床方法。这将是一项根本性的进步，将影响所有针对癫痫发作的癫痫治疗。