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利用时变格兰杰因果关系揭示WAG/Rij大鼠失神发作期间皮质-皮质和皮质-海马网络的变化。

Changes in corticocortical and corticohippocampal network during absence seizures in WAG/Rij rats revealed with time varying Granger causality.

作者信息

Sysoeva Marina V, Vinogradova Lyudmila V, Kuznetsova Galina D, Sysoev Ilya V, van Rijn Clementina M

机构信息

Yuri Gagarin State Technical University of Saratov, Saratov, Russia; Saratov Branch of Kotel'nokov's Institute of Radioengineering and Electronics of RAS, Saratov, Russia.

Institute of Higher Nervous Activity and Neurophysiology of RAS, Moscow, Russia.

出版信息

Epilepsy Behav. 2016 Nov;64(Pt A):44-50. doi: 10.1016/j.yebeh.2016.08.009. Epub 2016 Oct 11.

DOI:10.1016/j.yebeh.2016.08.009
PMID:27728902
Abstract

PURPOSE

Spike-and-wave discharges (SWDs) recorded in the cortical EEGs of WAG/Rij rats are the hallmark for absence epilepsy in this model. Although this type of epilepsy was long regarded as a form of primary generalized epilepsy, it is now recognized that there is an initiation zone - the perioral region of the somatosensory cortex. However, networks involved in spreading the seizure are not yet fully known. Previously, the dynamics of coupling between different layers of the perioral cortical region and between these zones and different thalamic nuclei was studied in time windows around the SWDs, using nonlinear Granger causality. The aim of the present study was to investigate, using the same method, the coupling dynamics between different regions of the cortex and between these regions and the hippocampus.

METHODS

Local field potentials were recorded in the frontal, parietal, and occipital cortices and in the hippocampus of 19 WAG/Rij rats. To detect changes in coupling reliably in a short time window, in order to provide a good temporal resolution, the innovative adapted time varying nonlinear Granger causality method was used. Mutual information function was calculated in addition to validate outcomes. Results of both approaches were tested for significance.

RESULTS

The SWD initiation process was revealed as an increase in intracortical interactions starting from 3.5s before the onset of electrographic seizure. The earliest preictal increase in coupling was directed from the frontal cortex to the parietal cortex. Then, the coupling became bidirectional, followed by the involvement of the occipital cortex (1.5s before SWD onset). There was no driving from any cortical region to hippocampus, but a slight increase in coupling from hippocampus to the frontoparietal cortex was observed just before SWD onset. After SWD onset, an abrupt drop in coupling in all studied pairs was observed. In most of the pairs, the decoupling rapidly disappeared, but driving force from hippocampus and occipital cortex to the frontoparietal cortex was reduced until the SWD termination.

CONCLUSION

Involvement of multiple cortical regions in SWD initiation shows the fundamental role of corticocortical feedback loops, forming coupling architecture and triggering the generalized seizure. The results add to the ultimate aim to construct a complete picture of brain interactions preceding and accompanying absence seizures in rats.

摘要

目的

在WAG/Rij大鼠皮质脑电图中记录到的棘慢波放电(SWDs)是该模型失神癫痫的标志。尽管这种类型的癫痫长期以来被视为原发性全身性癫痫的一种形式,但现在人们认识到存在一个起始区域——体感皮质的口周区域。然而,参与癫痫传播的网络尚未完全明确。此前,利用非线性格兰杰因果关系,在SWDs周围的时间窗口内研究了口周皮质区域不同层之间以及这些区域与不同丘脑核之间的耦合动力学。本研究的目的是使用相同的方法研究皮质不同区域之间以及这些区域与海马体之间的耦合动力学。

方法

在19只WAG/Rij大鼠的额叶、顶叶和枕叶皮质以及海马体中记录局部场电位。为了在短时间窗口内可靠地检测耦合变化,以提供良好的时间分辨率,使用了创新的自适应时变非线性格兰杰因果关系方法。此外,还计算了互信息函数以验证结果。对两种方法的结果进行了显著性检验。

结果

SWD起始过程表现为从脑电图发作开始前3.5秒起皮质内相互作用增加。最早的发作前耦合增加是从额叶皮质指向顶叶皮质。然后,耦合变为双向,随后枕叶皮质参与进来(SWD发作前1.5秒)。没有从任何皮质区域驱动到海马体,但在SWD发作前观察到从海马体到额顶叶皮质的耦合略有增加。SWD发作后,观察到所有研究的配对中耦合突然下降。在大多数配对中,解耦迅速消失,但从海马体和枕叶皮质到额顶叶皮质的驱动力降低,直到SWD终止。

结论

多个皮质区域参与SWD起始表明皮质皮质反馈回路的基本作用,形成耦合结构并触发全身性癫痫发作。这些结果有助于实现构建大鼠失神发作之前和伴随发作时大脑相互作用完整图景的最终目标。

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