Cortical deactivation induced by subcortical network dysfunction in limbic seizures.
Cortical deactivation induced by subcortical network dysfunction in limbic seizures.
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DOI：
10.1523/jneurosci.3846-09.2009
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发表时间：
2009-10-14
期刊：
影响因子：
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通讯作者：
Blumenfeld H
中科院分区：
文献类型：
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作者：
Englot DJ;Modi B;Mishra AM;DeSalvo M;Hyder F;Blumenfeld H
正常人类意识可能通过两种可能的途径受到损害：广泛皮质区域的功能直接降低，或皮质下激活系统的间接破坏。颞叶边缘癫痫发作损害意识的途径尚不清楚。我们最近开发了一种动物模型，与人类边缘癫痫发作一样，表现出新皮质失活，包括皮质慢波和皮质脑血流量（CBF）减少。我们现在通过功能性磁共振成像 (fMRI) 发现，电刺激大鼠海马癫痫发作会导致包括间隔区和内侧丘脑在内的皮质下结构活动增加，同时额叶、扣带回和压后皮质活动减少。海马体、隔膜和内侧丘脑的直接记录表明，快速多尖峰活动与神经元放电和 CBF 增加相关，而额叶皮层则显示缓慢振荡，与神经元放电和 CBF 减少相关。在没有癫痫发作的情况下，刺激间隔区，但不刺激海马或内侧丘脑，会导致皮质失活，伴有缓慢振荡和行为停止，类似于边缘系统癫痫发作期间看到的变化。横断穹窿是从海马体到皮质下结构的主要通道，消除了癫痫发作对皮质和行为的负面影响。通过诱导海马体和间隔区的同步活动，可以在穹窿受损的动物中重建皮质缓慢振荡和行为停滞，这意味着两个结构汇聚的下游区域都参与其中。这些发现表明，边缘系统癫痫发作可能通过皮质下功能受损间接导致新皮质失活。如果得到证实，皮质下网络可能代表旨在保留人类颞叶癫痫发作意识的治疗的目标。
Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions, or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model which, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional MRI (fMRI) that electrically-stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, while frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged upon by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures.