Dynamic Network Drivers of Seizure Generation, Propagation and Termination in Human Neocortical Epilepsy.
Dynamic Network Drivers of Seizure Generation, Propagation and Termination in Human Neocortical Epilepsy.
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DOI：
10.1371/journal.pcbi.1004608
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发表时间：
2015-12
影响因子：
4.3
通讯作者：
Bassett DS
中科院分区：
文献类型：
--
作者：
Khambhati AN;Davis KA;Oommen BS;Chen SH;Lucas TH;Litt B;Bassett DS
癫痫网络的特点是病理的、癫痫产生的“病灶”嵌入在结构和功能连接的网络中。临床上，癫痫病灶被认为是手术的最佳目标。然而，较差的手术结果表明病灶和周围网络之间存在复杂的关系，这种关系驱动了癫痫发作的动态。我们开发了一种新的技术，从颅内记录构建的动态功能网络中客观地跟踪癫痫发作状态。每一个动态状态都捕获了网络连接的独特模式，这些模式表明了神经群体的同步和不同步枢纽。我们的方法表明，当病灶附近的同步关系与周围癫痫网络中快速变化的非同步关系协同工作时，癫痫发作就会产生。随着癫痫发作的进展，网络连接的地形和几何变化加强和收紧了病灶附近的同步连接——这一机制可能有助于癫痫发作的终止。总的来说，我们的观察结果暗示了癫痫发作产生、传播和终止的分布皮层结构，并可能在确定用植入式装置调制哪些电路方面具有实际意义。定位相关性癫痫是一种使人衰弱的疾病，癫痫发作始于功能失调的大脑区域，并且通常对药物有抗药性。治疗患者的挑战是绘制随时间变化和驱动癫痫发作动态的皮质结构之间的联系。众所周知，全脑功能结构在任务期间会重新配置，我们假设癫痫网络在中观尺度上重新配置导致癫痫发作的产生、传播和终止。我们开发了新的方法来跟踪不同强度的连接之间的动态网络重构随着癫痫发作的发展。我们的研究结果表明，癫痫发作的产生主要是由快速重组的弱连接驱动的，随着癫痫发作的进展和终止，弱连接驱动更强的连接进一步加强和拓扑收紧。这些发现可能有实际的临床意义，针对特定的连接植入，治疗装置来控制癫痫发作。
The epileptic network is characterized by pathologic, seizure-generating ‘foci’ embedded in a web of structural and functional connections. Clinically, seizure foci are considered optimal targets for surgery. However, poor surgical outcome suggests a complex relationship between foci and the surrounding network that drives seizure dynamics. We developed a novel technique to objectively track seizure states from dynamic functional networks constructed from intracranial recordings. Each dynamical state captures unique patterns of network connections that indicate synchronized and desynchronized hubs of neural populations. Our approach suggests that seizures are generated when synchronous relationships near foci work in tandem with rapidly changing desynchronous relationships from the surrounding epileptic network. As seizures progress, topographical and geometrical changes in network connectivity strengthen and tighten synchronous connectivity near foci—a mechanism that may aid seizure termination. Collectively, our observations implicate distributed cortical structures in seizure generation, propagation and termination, and may have practical significance in determining which circuits to modulate with implantable devices. Localization-related epilepsy is a debilitating condition where seizures begin in dysfunctional brain regions, and is often resistant to medication. The challenge for treating patients is mapping connections between cortical structures that vary with time and drive seizure dynamics. While it is well known that whole-brain functional architecture reconfigures during tasks, we hypothesize that epileptic networks reconfigure at the meso-scale leading to seizure generation, propagation, and termination. We develop new methods to track dynamic network reconfiguration amongst connections of different strength as seizures evolve. Our results indicate that seizure generation is primarily driven by rapidly reorganizing weak connections that drive stronger connections to further strengthen and topographically tighten as seizures progress and terminate. These findings may have practical clinical implications for targeting specific connections with implantable, therapeutic devices to control seizures.