Pathological network activity in Parkinson's disease: from neural activity and connectivity to causality?
Pathological network activity in Parkinson's disease: from neural activity and connectivity to causality?
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DOI：
10.1093/brain/awq381
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
L. Timmermann;G. Fink
中科院分区：
文献类型：
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作者：
L. Timmermann;G. Fink
20年前Alexander等人首次描述了基底节丘脑皮质环的病理生理学变化。(1990)，通常被认为是帕金森氏病的关键症状的基础。在他们的模型中，Alexander等人。(1990)描述了基底节、丘脑和皮质不同亚核之间的抑制性和兴奋性联系的大型网络。在正常(即生理)状态下，有两个不同的环路调节基底节的活动：纹状体和苍白球内段之间的一个直接环路；以及该结构和纹状体之间的一个间接环路(在这个环路中，活动通过丘脑底核传递)。在健康状态下，这两个环路是平衡的，导致苍白球内段和黑质紧密相连的网状部的活动得到很好的调节。除了对脑干活动的影响外，这个基础神经节网络的“输出区”被认为投射到丘脑，从而调节丘脑-皮质的相互作用。尽管过于简单，但迄今为止，黑质致密部的多巴胺能神经元变性被认为是帕金森病的关键神经病理改变。根据神经病理学发现，在黑质多巴胺能细胞变性后，Alexander等人(1990年)的模型提出了间接环的影响，导致丘脑底核抑制减少，苍白球内段和黑质网状部受到更强的兴奋。相反，该模型预测纹状体对苍白球内段和实质网状部的直接抑制投射减少。这些变化的总和是苍白球内侧部分和实质网状部的“过度活动”，以及丘脑-皮质相互作用的抑制。然后这个模型就可以…
Pathophysiological changes in the basal ganglia thalamocortical loops, first described ∼20 years ago by Alexander et al . (1990), are commonly assumed to underlie key symptoms of Parkinson's disease. In their model, Alexander et al . (1990) described a large network of inhibitory and excitatory connections between different subnuclei of basal ganglia, thalamus and cortex. In the normal (i.e. physiological) state, two distinct loops regulate basal ganglia activity: a direct loop between the striatum and the internal segment of the globus pallidus; and an indirect loop between this structure and the striatum (in this loop, activity is relayed via the subthalamic nucleus). In the healthy state, these two loops are balanced resulting in well-regulated activity of the internal segment of the globus pallidus and the tightly connected pars reticulata of the substantia nigra. Besides its influence on brainstem activity, the ‘output-region’ of this basal ganglia network is assumed to project to the thalamus, thereby modulating thalamo-cortical interactions. Albeit simplistic, the degeneration of dopaminergic neurons in the pars compacta of the substantia nigra is to date considered the key neuropathological change underlying Parkinson's disease. Based upon neuropathological findings, after degeneration of dopaminergic cells in the substantia nigra the Alexander et al .'s (1990) model proposes affection of the indirect loop leading to reduced inhibition of the subthalamic nucleus, and stronger excitation of the internal segment of the globus pallidus and the pars reticulata of the substantia nigra. Conversely, the model predicts that the direct inhibitory projections of the striatum to the internal segment of the globus pallidus and the pars reticulata of the substantia are reduced. The sum effects of these changes are ‘overactivity’ in the internal segment of the globus pallidus and the pars reticulata of the substantia and an inhibition of thalamo-cortical interactions. This model could then …