病理性高频振荡在新皮质癫痫发生中的作用和机制研究

The epileptogenic zone in neocortical epilepsy can be a complicated network, which is difficult to be localized by routine methods. High frequency oscillation (HFO), a tiny EEG signal recorded by intracranial EEG, is closely related to seizure generation. More recently, HFOs are found to be closely related to epileptogenic zone in clinic and provide useful information in making the surgical plan. Current HFO studies were usually based on mesial temporal epilepsy. However,in neocortical epilepsy, the distribution, role in seizure generation, relationship with epileptogenic zone as well as the cellular mechanism of HFO remains unknown. We have explored the HFO distribution in patients with neocortical epilepsy and found that both physiological HFOs and pathological HFO (pHFO) exist in human neocortex. Furthermore, the pHFOs were multi-focally distributed; and the pHFO foci may be inter-connected and the interaction may participate ictogenesis. Here we plan to study the role of pHFO and pHFO network in seizure generation of neocortical epilepsy in clinical level as well as in animal epilepsy model using a combination of macro-electrode and micro-electrode. We also plan to elucidate the cellular mechanism of neocortical pHFO generation using microelectrode array. Our project will help to understand neocortical epilepsy generation and epileptogenic network; it can also promotes pHFO application in localizing epileptogenic zone in neocortical epilepsy.

新皮质癫痫的致痫区可能具有网络特征，常规方法较难准确定位。近年的研究表明，颅内脑电图中的高频振荡（HFO）与癫痫的形成和发作密切相关，癫痫患者脑内的HFO还可能帮助定位致痫区，指导癫痫手术。但是，目前HFO的研究一般基于颞叶内侧面癫痫，HFO在新皮质癫痫中的分布、作用、与致痫区的关系，以及产生机制都还有待进一步研究。申请人在前期研究中发现癫痫患者大脑新皮质中的病理性HFO (pHFO)与癫痫发生紧密联系，而且pHFO的分布还具有多灶性特点，pHFO灶点之间可能通过相互联系和相互作用导致癫痫发作。课题组拟在临床研究和整体动物模型两个层次上，以常规电极、微电极和微电极阵列的多维度记录手段，阐明pHFO和pHFO网络在新皮质癫痫发生中的作用，并明确pHFO产生的细胞机制。本项目不仅能加深对新皮质癫痫发生机制和致痫区网络学说的认识，还能为临床致痫区定位提供指导。

在临床和动物模型两个层次，课题组分析了病理性高频震荡（pHFO）与癫痫发生的关系，阐明了它在新皮质癫痫中的变化特征。我们为接受慢性颅内电极埋藏的癫痫患者（观察对象主要为局灶性脑皮质发育障碍的患者）进行宽频脑电图采集和分析，观察到I型ripple和fast ripple同样具有病理特性，I型ripple比fast ripple更容易记录到，不完全切除I型ripple的产生区域会增加癫痫的远期复发风险（6个月后）；而fast ripple区域的不完全切除会增加癫痫早期复发（6个月内）的风险。它们对标记致痫区均有意义，都是有价值的癫痫标记物（epilepsy marker）。我们还意外观察到了在新皮质癫痫和颞叶内侧面癫痫中，癫痫发作期的高频震荡（HFO）具有不同的演变特点，在前者中ripple波增加，在后者中ripple波反而减少。我们在动物模型中观察了后者的变化规律，发现癫痫发作前II型ripple的减少比I型ripple减少更为明显。这提示两类ripple的发生机制不同。本研究阐明解致痫网络提供了新的视角，也为提高临床癫痫手术疗效或者癫痫预测提供了理论帮助。

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