Emergent Functional Network Effects in Parkinson Disease
Emergent Functional Network Effects in Parkinson Disease
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DOI：
10.1093/cercor/bhy121
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发表时间：
2019-06-01
期刊：
影响因子：
3.7
通讯作者：
Campbell, Meghan C.
中科院分区：
文献类型：
--
作者：
Gratton, Caterina;Koller, Jonathan M.;Campbell, Meghan C.
帕金森病(PD)的标志性病理是进行性突触核病，始于尾侧脑干，后来向吻部扩散。然而，主要的皮质下病理不能解释帕金森病广泛的临床表现。为了与这些观察结果相一致，可以使用静息状态功能连接(FC)来检查分布在不同大脑网络上的功能障碍。我们对非痴呆性帕金森病(N=107；停药)和健康对照组(N=46)进行了一项大型单点研究，结合严格的质量控制措施和对皮质、皮质下和小脑区域的全面采样，测量了FC。我们使用了新的统计方法来确定整个连接体、网络水平和特定大脑区域的组差异。群体差异尊重具有良好特征的网络描述，从而产生网络到网络效应的显著“区块式”模式。令人惊讶的是，这些结果表明，最大的FC差异涉及感觉运动、丘脑和小脑网络，纹状体的影响明显较小。对半重复实验证明了这些结果的稳健性。最后，功能障碍与行为的区块相关性表明，功能障碍的中断可能有助于帕金森病的临床表现。总体而言，这些结果表明功能网络相互作用的协调崩溃，远离主要的病理生理学，并表明帕金森病的FC缺陷与紧急网络水平现象有关，而不是局灶性病理。
The hallmark pathology underlying Parkinson disease (PD) is progressive synucleinopathy, beginning in caudal brainstem that later spreads rostrally. However, the primarily subcortical pathology fails to account for the wide spectrum of clinical manifestations in PD. To reconcile these observations, resting-state functional connectivity (FC) can be used to examine dysfunction across distributed brain networks. We measured FC in a large, single-site study of nondemented PD (N = 107; OFF medications) and healthy controls (N = 46) incorporating rigorous quality control measures and comprehensive sampling of cortical, subcortical and cerebellar regions. We employed novel statistical approaches to determine group differences across the entire connectome, at the network-level, and for select brain regions. Group differences respected well-characterized network delineations producing a striking "block-wise" pattern of network-to-network effects. Surprisingly, these results demonstrate that the greatest FC differences involve sensorimotor, thalamic, and cerebellar networks, with notably smaller striatal effects. Split-half replication demonstrates the robustness of these results. Finally, block-wise FC correlations with behavior suggest that FC disruptions may contribute to clinical manifestations in PD. Overall, these results indicate a concerted breakdown of functional network interactions, remote from primary pathophysiology, and suggest that FC deficits in PD are related to emergent network-level phenomena rather than focal pathology.