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癫痫发生大鼠模型中功能脑网络的改变:一项纵向静息态 fMRI 研究。

Alterations in the functional brain network in a rat model of epileptogenesis: A longitudinal resting state fMRI study.

机构信息

MEDISIP, Department of Electronics and Information Systems, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium.

4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium.

出版信息

Neuroimage. 2019 Nov 15;202:116144. doi: 10.1016/j.neuroimage.2019.116144. Epub 2019 Aug 29.

DOI:10.1016/j.neuroimage.2019.116144
PMID:31473355
Abstract

Epilepsy is a neurological disorder characterized by recurrent epileptic seizures. Electrophysiological and neuroimaging studies in patients with epilepsy suggest that abnormal functional brain networks play a role in the development of epilepsy, i.e. epileptogenesis, resulting in the generation of spontaneous seizures and cognitive impairment. In this longitudinal study, we investigated changes in functional brain networks during epileptogenesis in the intraperitoneal kainic acid (IPKA) rat model of temporal lobe epilepsy (TLE) using resting state functional magnetic resonance imaging (rsfMRI) and graph theory. Additionally, we investigated whether these changes are related to the frequency of occurrence of spontaneous epileptic seizures in the chronic phase of epilepsy. Using a 7T MRI system, rsfMRI images were acquired under medetomidine anaesthesia before and 1, 3, 6, 10 and 16 weeks after status epilepticus (SE) induction in 20 IPKA animals and 7 healthy control animals. To obtain a functional network, correlation between fMRI time series of 38 regions of interest (ROIs) was calculated. Then, several graph theoretical network measures were calculated to describe and quantify the network changes. At least 17 weeks post-SE, IPKA animals were implanted with electrodes in the left and right dorsal hippocampus, EEG was measured for 7 consecutive days and spontaneous seizures were counted. Our results show that correlation coefficients of fMRI time series shift to lower values during epileptogenesis, indicating weaker whole brain network connections. Segregation and integration in the functional brain network also decrease, indicating a lower local interconnectivity and a lower overall communication efficiency. Secondly, this study demonstrates that the largest decrease in functional connectivity is observed for the retrosplenial cortex. Finally, post-SE changes in functional connectivity, segregation and integration are correlated with seizure frequency in the IPKA rat model.

摘要

癫痫是一种以反复癫痫发作为特征的神经系统疾病。癫痫患者的电生理学和神经影像学研究表明,异常的功能性大脑网络在癫痫的发展中起作用,即癫痫发生,导致自发性癫痫发作和认知障碍的产生。在这项纵向研究中,我们使用静息态功能磁共振成像(rsfMRI)和图论研究了腹腔内海人酸(ipka)颞叶癫痫(tle)大鼠模型在癫痫发生过程中功能性大脑网络的变化。此外,我们还研究了这些变化是否与癫痫慢性期自发性癫痫发作的频率有关。使用 7t MRI 系统,在诱导癫痫持续状态(SE)前和 SE 后 1、3、6、10 和 16 周,对 20 只 ipka 动物和 7 只健康对照动物进行了麻醉下的 rsfMRI 图像采集。为了获得功能网络,计算了 38 个感兴趣区(ROI)的 fMRI 时间序列之间的相关性。然后,计算了几个图论网络度量来描述和量化网络变化。至少在 SE 后 17 周,ipka 动物被植入左、右背侧海马电极,连续 7 天测量 EEG,并计数自发性癫痫发作。我们的结果表明,在癫痫发生过程中,fMRI 时间序列的相关系数向较低的值转移,表明整个大脑网络的连接较弱。功能性大脑网络的分离和整合也减少,表明局部互连性较低,整体通信效率较低。其次,本研究表明,在癫痫发生过程中,功能连接的最大减少发生在后扣带回皮层。最后,IPKA 大鼠模型 SE 后功能连接、分离和整合的变化与癫痫发作频率相关。

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