Warren Aaron E L, Abbott David F, Vaughan David N, Jackson Graeme D, Archer John S
Department of Medicine, The University of Melbourne, Heidelberg, Victoria, Australia.
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.
Epilepsia. 2016 May;57(5):812-22. doi: 10.1111/epi.13342. Epub 2016 Mar 6.
In patients with Lennox-Gastaut syndrome (LGS), recurrent epileptic activity is thought to contribute to impaired cognition (epileptic encephalopathy). Using concurrent electroencephalography-functional magnetic resonance imaging (EEG-fMRI), we recently showed that epileptiform discharges in LGS recruit large-scale networks that normally support key cognitive processes. In LGS, given that epileptic activity engages cognitive networks, and cognition is pervasively impaired, we hypothesized that cognitive network interactions in LGS are persistently abnormal.
We studied 15 LGS patients (mean age ± 1 standard deviation [SD] = 28.7 ± 10.6 years) and 17 healthy controls (mean age ± 1 SD = 27.6 ± 6.6 years) using task-free EEG-fMRI. Four networks of interest (default-mode, dorsal attention, executive control, and anterior salience) were defined using group-level independent components analysis (ICA). Functional connectivity within and between networks was determined for each subject, and then LGS network interactions were compared to network behavior in the control group. To test whether group differences were present in periods without scalp-detectable epileptiform discharges (i.e., persistent), we separately assessed discharge-affected and discharge-unaffected epochs in six patients with sufficient data for this analysis.
In LGS, cognitive networks showed (1) reduced within-network integration, including weaker connectivity within the default-mode network, and (2) impaired between-network segregation, including stronger connectivity between the default-mode and dorsal attention networks. Abnormal interactions were present during fMRI periods with and without discharges, indicating that impaired network behavior may endure during periods without scalp-detectable epileptic activity.
In LGS, cognitive network interactions are persistently abnormal. Given that cognition typically worsens with the onset of LGS, and may improve after seizure control, our findings are consistent with the hypothesis that the epileptic process in LGS may initiate and perhaps sustain abnormal network behavior. We propose that epileptic encephalopathy may be a consequence of persistently disrupted cognitive network interactions.
在Lennox-Gastaut综合征（LGS）患者中，反复的癫痫活动被认为会导致认知障碍（癫痫性脑病）。我们最近使用同步脑电图-功能磁共振成像（EEG-fMRI）研究发现，LGS中的癫痫样放电会激活通常支持关键认知过程的大规模网络。在LGS中，鉴于癫痫活动会涉及认知网络，且认知普遍受损，我们推测LGS中的认知网络相互作用持续异常。
我们使用静息态EEG-fMRI对15例LGS患者（平均年龄±1标准差[SD]=28.7±10.6岁）和17名健康对照者（平均年龄±1 SD=27.6±6.6岁）进行了研究。使用组水平独立成分分析（ICA）定义了四个感兴趣的网络（默认模式、背侧注意、执行控制和前凸显网络）。确定了每个受试者网络内和网络间的功能连接，然后将LGS的网络相互作用与对照组的网络行为进行比较。为了测试在无头皮可检测到的癫痫样放电期间（即持续性期间）是否存在组间差异，我们对六例有足够数据进行此分析的患者分别评估了受放电影响和未受放电影响的时间段。
在LGS中，认知网络表现出：（1）网络内整合减少，包括默认模式网络内连接性减弱；（2）网络间分离受损，包括默认模式网络和背侧注意网络之间连接性增强。在有放电和无放电的fMRI期间均存在异常相互作用，这表明在无头皮可检测到的癫痫活动期间，受损的网络行为可能持续存在。
在LGS中，认知网络相互作用持续异常。鉴于认知通常在LGS发作时恶化，且在癫痫控制后可能改善，我们的研究结果与以下假设一致，即LGS中的癫痫过程可能引发并可能维持异常的网络行为。我们提出，癫痫性脑病可能是认知网络相互作用持续中断的结果。
