Altered canonical and striatal-frontal resting state functional connectivity in children with pathogenic variants in the Ras/mitogen-activated protein kinase pathway.
Altered canonical and striatal-frontal resting state functional connectivity in children with pathogenic variants in the Ras/mitogen-activated protein kinase pathway.
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在RAS/有丝分裂原激活的蛋白激酶途径中具有致病性变异的儿童的儿童的规范和纹状体额叶静息状态功能连通性。
DOI：
10.1038/s41380-021-01422-5
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发表时间：
2022-03
影响因子：
11
通讯作者：
Green T
中科院分区：
文献类型：
--
作者：
Bruno JL;Shrestha SB;Reiss AL;Saggar M;Green T
越来越多的证据支持Ras/丝裂原活化蛋白激酶（Ras/MAPK）通路在神经发育障碍中的作用。在这里，作者使用遗传学优先的方法来研究Ras/MAPK致病变异如何影响大脑的功能组织和认知表型，包括注意力和抑制的弱点。应用功能MRI检测努南综合征（NS）患儿静息状态功能连接（RSFC）与Ras/MAPK致病变异的关系。参与者（年龄4-12岁）包括39名NS患儿（平均年龄8.44岁，SD=2.20, 25名女性）和49名典型发育（TD）患儿（平均年龄9.02，SD=9.02, 33名女性）。NS组28名儿童和TD组46名儿童有可用的MRI数据，并纳入最终分析。结果显示，NS组在典型视觉、腹侧注意、左额顶叶和边缘网络内具有显著的超连通性（p<0.05 FWE）。典型左额顶叶和边缘网络内较高的连通性与NS内的认知功能呈正相关，但与TD组无关。此外，NS组在基于种子的纹状叶-额叶连通性方面表现出显著的组间差异（Z>2.6, p<0.05 FWE）。典型脑网络中的超连通性可能代表了Ras/MAPK致病变异和认知表型之间的中间表型，包括注意力和抑制的弱点。纹状体-额叶连通性的改变与纹状体体积的缩小和白质连通性的改变相对应。这些结果可能表明延迟成熟和代偿机制，它们对于理解NS和更广泛的神经发育障碍儿童群体中认知表型的病理生理学是重要的。
Mounting evidence supports the role of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway in neurodevelopmental disorders. Here, the authors used a genetics-first approach to examine how Ras/MAPK pathogenic variants affect the functional organization of the brain and cognitive phenotypes including weaknesses in attention and inhibition. Functional MRI was used to examine resting state functional connectivity (RSFC) in association with Ras/MAPK pathogenic variants in children with Noonan syndrome (NS). Participants (age 4–12 years) included 39 children with NS (mean age 8.44, SD=2.20, 25 females) and 49 typically developing (TD) children (mean age 9.02, SD=9.02, 33 females). Twenty-eight children in the NS group and 46 in the TD group had usable MRI data and were included in final analyses. The results indicated significant hyperconnectivity for the NS group within canonical visual, ventral attention, left frontoparietal and limbic networks (p<0.05 FWE). Higher connectivity within canonical left frontoparietal and limbic networks positively correlated with cognitive function within the NS but not the TD group. Further, the NS group demonstrated significant group differences in seed-based striatal-frontal connectivity (Z>2.6, p<0.05 FWE). Hyperconnectivity within canonical brain networks may represent an intermediary phenotype between Ras/MAPK pathogenic variants and cognitive phenotypes, including weaknesses in attention and inhibition. Altered striatal-frontal connectivity corresponds with smaller striatal volume and altered white matter connectivity previously documented in children with NS. These results may indicate delayed maturation and compensatory mechanisms and they are important for understanding the pathophysiology underlying cognitive phenotypes in NS and in the broader population of children with neurodevelopmental disorders.
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影响因子：
5.7
作者：
Beckmann, CF;Jenkinson, M;Smith, SM
通讯作者：
Smith, SM
影响因子：
30.8
作者：
Goyal Y;Jindal GA;Pelliccia JL;Yamaya K;Yeung E;Futran AS;Burdine RD;Schüpbach T;Shvartsman SY
通讯作者：
Shvartsman SY
影响因子：
16.6
作者：
Bunda S;Burrell K;Heir P;Zeng L;Alamsahebpour A;Kano Y;Raught B;Zhang ZY;Zadeh G;Ohh M
通讯作者：
Ohh M
DOI：
10.1073/pnas.0811168106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Honey, C. J.;Sporns, O.;Hagmann, P.
通讯作者：
Hagmann, P.
影响因子：
3.7
作者：
Green, Tamar;Saggar, Manish;Reiss, Allan L.
通讯作者：
Reiss, Allan L.