Engels Marjolein M A, Stam Cornelis J, van der Flier Wiesje M, Scheltens Philip, de Waal Hanneke, van Straaten Elisabeth C W
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Department of Clinical Neurophysiology and MEG center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
BMC Neurol. 2015 Aug 20;15:145. doi: 10.1186/s12883-015-0400-7.
EEG studies have shown that patients with Alzheimer's disease (AD) have weaker functional connectivity than controls, especially in higher frequency bands. Furthermore, active regions seem more prone to AD pathology. How functional connectivity is affected in AD subgroups of disease severity and how network hubs (highly connected brain areas) change is not known. We compared AD patients with different disease severity and controls in terms of functional connections, hub strength and hub location.
We studied routine 21-channel resting-state electroencephalography (EEG) of 318 AD patients (divided into tertiles based on disease severity: mild, moderate and severe AD) and 133 age-matched controls. Functional connectivity between EEG channels was estimated with the Phase Lag Index (PLI). From the PLI-based connectivity matrix, the minimum spanning tree (MST) was derived. For each node (EEG channel) in the MST, the betweenness centrality (BC) was computed, a measure to quantify the relative importance of a node within the network. Then we derived color-coded head plots based on BC values and calculated the center of mass (the exact middle had x and y values of 0). A shifting of the hub locations was defined as a shift of the center of mass on the y-axis across groups. Multivariate general linear models with PLI or BC values as dependent variables and the groups as continuous variables were used in the five conventional frequency bands.
We found that functional connectivity decreases with increasing disease severity in the alpha band. All, except for posterior, regions showed increasing BC values with increasing disease severity. The center of mass shifted from posterior to more anterior regions with increasing disease severity in the higher frequency bands, indicating a loss of relative functional importance of the posterior brain regions.
In conclusion, we observed decreasing functional connectivity in the posterior regions, together with a shifted hub location from posterior to central regions with increasing AD severity. Relative hub strength decreases in posterior regions while other regions show a relative rise with increasing AD severity, which is in accordance with the activity-dependent degeneration theory. Our results indicate that hubs are disproportionally affected in AD.
脑电图研究表明，阿尔茨海默病（AD）患者的功能连接性比对照组弱，尤其是在高频波段。此外，活跃区域似乎更容易出现AD病理改变。疾病严重程度不同的AD亚组中功能连接性如何受到影响以及网络枢纽（高度连接的脑区）如何变化尚不清楚。我们在功能连接、枢纽强度和枢纽位置方面对不同疾病严重程度的AD患者和对照组进行了比较。
我们研究了318例AD患者（根据疾病严重程度分为三分位数：轻度、中度和重度AD）和133例年龄匹配的对照组的常规21通道静息态脑电图（EEG）。采用相位滞后指数（PLI）估计EEG通道之间的功能连接性。从基于PLI的连接矩阵中导出最小生成树（MST）。对于MST中的每个节点（EEG通道），计算中介中心性（BC），这是一种量化节点在网络中相对重要性的指标。然后我们根据BC值导出彩色编码的头部图，并计算质心（精确中心的x和y值为0）。枢纽位置的移动定义为质心在y轴上跨组的移动。在五个传统频段中，使用以PLI或BC值为因变量、组为连续变量的多变量一般线性模型。
我们发现，在α波段，功能连接性随疾病严重程度的增加而降低。除后部区域外，所有区域的BC值均随疾病严重程度的增加而增加。在高频波段，质心随着疾病严重程度的增加从后部区域转移到更前部区域，表明后脑区域的相对功能重要性丧失。
总之，我们观察到后部区域的功能连接性降低，同时随着AD严重程度的增加，枢纽位置从后部区域转移到中部区域。后部区域的相对枢纽强度降低，而其他区域随着AD严重程度的增加呈现相对上升，这与活动依赖的退化理论一致。我们的结果表明，枢纽在AD中受到的影响不成比例。
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