Alterations in functional connectivity in children with autism spectrum disorder: an eigen-microstate analysis-based functional MRI study
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摘要: 基于神经影像的人脑连接组学研究表明，孤独症患者脑功能网络连接模式呈现异常特征．然而，以往研究主要集中在静态功能连接方面，孤独症患者脑功能网络连接模式的多样性及其异常特征仍有待进一步阐明．本研究采用45名6~10岁男性儿童（27名孤独症和18名正常发育儿童）的静息态功能磁共振影像，开展了全脑功能活动时间序列的本征微观态分析．研究发现，正常发育儿童与孤独症儿童的全脑自发功能活动均由6个活动模态所主导．每个主导模态具有不同的空间分布特征，并且对应于一种功能系统依赖的连接模式．相较于正常发育儿童，孤独症儿童在第一、第二以及第四主导模态上呈现功能连接的异常增强或者减弱，主要涉及视觉网络内连接，以及背侧注意网络与额顶网络、默认网络和视觉网络之间的连接．这些结果表明，孤独症儿童脑功能网络的异常连接模式存在多样性，为深入理解孤独症脑网络异常机制提供了新颖见解．Abstract: Neuroimaging studies of human brain connectomics have revealed abnormal functional connectivity patterns in individuals with autism spectrum disorder (ASD)． Previous works primarily focused on static functional connectivity, but diversity in functional connectivity patterns and their abnormal features in ASD remains to be elucidated． Statistical eigen-microstate analysis of resting-state functional magnetic resonance imaging data from 45 children (6-10 years old, all males) was performed in this study, which included 27 children with ASD and 18 healthy controls． It was found that certain (i.e., six in total) leading basic modes made a dominant contribution to whole-brain spontaneous activity for both healthy children and children with ASD． Each leading mode showed distinct spatial distribution of brain activity and corresponded to functional system-dependent connectivity pattern． Compared to healthy developing children, children with ASD showed altered functional connectivity patterns for the first, second, and fourth leading modes, primarily involving connectivity within the visual network and connectivity between the dorsal attention network and the frontoparietal, default-mode, and visual networks． These data suggest that multiple abnormal connectivity patterns simultaneously occur in functional brain networks of children with ASD, offering novel insights into mechanisms underlying brain network alterations in autism．
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Key words:
- autism spectrum disorder /
- children /
- magnetic resonance imaging /
- eigen-microstate /
- brain networks
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图 2 正常发育儿童与孤独症儿童功能活动的各主导模态对应的功能连接模式（系统水平）
每个主导模态对应的功能连接模式定义为该主导模态中所有脑节点对之间的共激活模式．对于孤独症儿童，调整第3个与第4个主导模态的排序，以保持与正常发育儿童的空间对应性．
图 3 相较正常发育儿童，孤独症儿童脑功能网络的异常连接模式
a. 孤独症儿童在系统水平的连接模式差异；b. 孤独症儿童异常功能连接的空间分布．图中红色表明孤独症儿童的共激活模式高于正常发育儿童，蓝色表明孤独症儿童的共激活模式低于正常发育儿童．a中，＊标注显著差异（P < 0.05，FDR校正）；b中呈现各脑节点涉及的显著改变连接的数量，这些连接满足P < 0.05，FDR校正．
表 1 儿童受试者的人口统计学信息
参数 ASD (n = 27) TD (n = 18) P组间对比1） 年龄/岁 7.1~10.9 (9.2±1.2) 6.5~10.8 (9.1±1.4) 0.80 全量表智商 80~138 (109.2±17.8) 76~148 (112.3±12.5) 0.50 头动/mm2） 0.03~0.19 (0.10±0.05) 0.02~0.12 (0.06±0.02) 0.43 1）基于双样本t检验；2）头动指标采用平均逐帧位移．每个指标均给出数值范围以及均值与标准差． 
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