Dynamic Functional Connectivity Alterations and Their Associated Gene Expression Pattern in Autism Spectrum Disorders.
Dynamic Functional Connectivity Alterations and Their Associated Gene Expression Pattern in Autism Spectrum Disorders.
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自闭症谱系障碍中的动态功能连接改变及其相关基因表达模式
DOI：
10.3389/fnins.2021.794151
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发表时间：
2021
影响因子：
4.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Ma L;Yuan T;Li W;Guo L;Zhu D;Wang Z;Liu Z;Xue K;Wang Y;Liu J;Man W;Ye Z;Liu F;Wang J
自闭症谱系障碍（ASDs）是一组异质性神经发育障碍，具有高度遗传性，并与动态功能连接受损（DFC）相关。然而，DFC改变背后的分子机制在很大程度上仍然未知。本研究纳入了来自自闭症脑成像数据交换II数据库的88名asd患者和87名人口统计学匹配的典型对照（tc）。然后采用基于种子的滑动窗口方法来研究10个经典静息状态功能网络和整个大脑中29个种子中的每一个种子的DFC变化。随后，评估asd患者DFC改变与其症状严重程度之间的关系。最后，进行转录-神经影像学关联分析，探讨asd患者DFC中断的分子机制。与tc相比，asd患者右侧背外侧前额叶皮层（DLPFC）与左侧梭状回/舌回之间、DLPFC与颞上回之间、右侧额叶视野（FEF）与左侧额叶中回之间、FEF与右侧角回之间、左侧顶叶内沟与右侧颞中回之间的DFC显著增加。此外，观察到DFC改变与症状严重程度之间存在显著关系。此外，通过从Allen人脑图谱中提取的6个供体大脑的基因表达与病例对照DFC差异之间进行基因跨样本空间相关性分析，确定了与asd中DFC变化相关的基因。在富集分析中，这些基因在突触信号、电压门控离子通道和钙通路相关的过程中富集；此外，这些基因在自闭症、慢性酒精中毒和一些与抑郁症相关的疾病中高度表达。这些结果不仅表明asd患者的DFC更高，而且为这些改变背后的分子机制提供了新的见解。
Autism spectrum disorders (ASDs) are a group of heterogeneous neurodevelopmental disorders that are highly heritable and are associated with impaired dynamic functional connectivity (DFC). However, the molecular mechanisms behind DFC alterations remain largely unknown. Eighty-eight patients with ASDs and 87 demographically matched typical controls (TCs) from the Autism Brain Imaging Data Exchange II database were included in this study. A seed-based sliding window approach was then performed to investigate the DFC changes in each of the 29 seeds in 10 classic resting-state functional networks and the whole brain. Subsequently, the relationships between DFC alterations in patients with ASDs and their symptom severity were assessed. Finally, transcription-neuroimaging association analyses were conducted to explore the molecular mechanisms of DFC disruptions in patients with ASDs. Compared with TCs, patients with ASDs showed significantly increased DFC between the right dorsolateral prefrontal cortex (DLPFC) and left fusiform/lingual gyrus, between the DLPFC and the superior temporal gyrus, between the right frontal eye field (FEF) and left middle frontal gyrus, between the FEF and the right angular gyrus, and between the left intraparietal sulcus and the right middle temporal gyrus. Moreover, significant relationships between DFC alterations and symptom severity were observed. Furthermore, the genes associated with DFC changes in ASDs were identified by performing gene-wise across-sample spatial correlation analysis between gene expression extracted from six donors’ brain of the Allen Human Brain Atlas and case-control DFC difference. In enrichment analysis, these genes were enriched for processes associated with synaptic signaling and voltage-gated ion channels and calcium pathways; also, these genes were highly expressed in autistic disorder, chronic alcoholic intoxication and several disorders related to depression. These results not only demonstrated higher DFC in patients with ASDs but also provided novel insight into the molecular mechanisms underlying these alterations.
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影响因子：
5.7
作者：
Behroozmand R;Shebek R;Hansen DR;Oya H;Robin DA;Howard MA 3rd;Greenlee JD
通讯作者：
Greenlee JD
影响因子：
13.5
作者：
Bhat S;El-Kasaby A;Freissmuth M;Sucic S
通讯作者：
Sucic S
影响因子：
3.9
作者：
Charlton, Anna S.;Smith, Isaac C.;White, Susan W.
通讯作者：
White, Susan W.
影响因子：
11
作者：
Di Martino, A.;Yan, C-G;Li, Q.;Denio, E.;Castellanos, F. X.;Alaerts, K.;Anderson, J. S.;Assaf, M.;Bookheimer, S. Y.;Dapretto, M.;Deen, B.;Delmonte, S.;Dinstein, I.;Ertl-Wagner, B.;Fair, D. A.;Gallagher, L.;Kennedy, D. P.;Keown, C. L.;Keysers, C.;Lainhart, J. E.;Lord, C.;Luna, B.;Menon, V.;Minshew, N. J.;Monk, C. S.;Mueller, S.;Mueller, R. A.;Nebel, M. B.;Nigg, J. T.;O'Hearn, K.;Pelphrey, K. A.;Peltier, S. J.;Rudie, J. D.;Sunaert, S.;Thioux, M.;Tyszka, J. M.;Uddin, L. Q.;Verhoeven, J. S.;Wenderoth, N.;Wiggins, J. L.;Mostofsky, S. H.;Milham, M. P.
通讯作者：
Milham, M. P.
影响因子：
3.7
作者：
Allen, Elena A.;Damaraju, Eswar;Calhoun, Vince D.
通讯作者：
Calhoun, Vince D.