背景:越来越多的证据表明儿童生长激素缺乏症(GHD)的区域灰质(GM)形态改变;然而,这些患者的大规模脑形态网络(MBN)尚不清楚.
目的:探讨儿童GHD个体水平MBN的拓扑组织。
方法:纳入61例GHD和42例典型发展中对照(TD)。利用GM的区域间形态相似性构建个体水平的MBN。比较了拓扑参数的组间差异和基于网络的统计分析。最后,分析网络特性与临床变量之间的关联关系。
结果:与TD相比,GHD表明正常的小世界组织受到干扰,反映在Lp增加,γ,λ,σ和降低的Cp,Eglob(所有PFDR<0.017)。关于节点属性,GHD在小脑4-5,与中央执行网络相关的左额下回表现出增加的淋巴结轮廓,边缘区相关的右后扣带回,左海马,和双侧苍白球,丘脑(所有PFDR<0.05)。同时,GHD在感觉运动网络相关的双侧中央旁小叶表现出减少的结节轮廓,默认模式网络相关的左额上回,与视觉网络相关的右舌回,听觉网络相关的右颞上回和双侧杏仁核,右侧小脑3,双侧小脑10,疣1-2,3,4-5,6(PFDR均<0.05)。此外,GHD组的血清标志物和行为评分与淋巴结改变相关(P≤0.046,未校正).
结论:GHD在大规模个体水平MBN中经历了广泛的重组,可能是由于皮质-纹状体-丘脑-小脑环异常,皮质-边缘-小脑,背侧视觉-感觉运动-纹状体,和小脑听觉电路.这项研究强调了GHD背后异常形态连接的关键作用,这可能会导致它们在运动方面的发展相对较慢,认知,和行为问题表现中的语言功能。
BACKGROUND: Accumulating evidences indicate regional grey matter (GM) morphology alterations in pediatric growth hormone deficiency (GHD); however, large-scale morphological brain networks (MBNs) undergo these patients remains unclear.
OBJECTIVE: To investigate the topological organization of individual-level MBNs in pediatric GHD.
METHODS: Sixty-one GHD and 42 typically developing controls (TDs) were enrolled. Inter-regional morphological similarity of GM was taken to construct individual-level MBNs. Between-group differences of topological parameters and network-based statistics analysis were compared. Finally, association relationship between network properties and clinical variables was analyzed.
RESULTS: Compared to TDs, GHD indicated a disturbance in the normal small-world organization, reflected by increased Lp, γ, λ, σ and decreased Cp, Eglob (all PFDR < 0.017). Regarding nodal properties, GHD exhibited increased nodal profiles at cerebellum 4-5, central executive network-related left inferior frontal gyrus, limbic regions-related right posterior cingulate gyrus, left hippocampus, and bilateral pallidum, thalamus (all PFDR < 0.05). Meanwhile, GHD exhibited decreased nodal profiles at sensorimotor network -related bilateral paracentral lobule, default-mode network-related left superior frontal gyrus, visual network -related right lingual gyrus, auditory network-related right superior temporal gyrus and bilateral amygdala, right cerebellum 3, bilateral cerebellum 10, vermis 1-2, 3, 4-5, 6 (all PFDR < 0.05). Furthermore, serum markers and behavior scores in GHD group were correlated with altered nodal profiles (P ≤ 0.046, uncorrected).
CONCLUSIONS: GHD undergo an extensive reorganization in large-scale individual-level MBNs, probably due to abnormal cortico-striatal-thalamo-cerebellum loops, cortico-limbic-cerebellum, dorsal visual-sensorimotor-striatal, and auditory-cerebellum circuitry. This study highlights the crucial role of abnormal morphological connectivity underlying GHD, which might result in their relatively slower development in motor, cognitive, and linguistic functional within behavior problem performance.