Li Cuicui, Li Tong, Chen Ying, Zhang Chunling, Ning Mingmin, Qin Rui, Li Lin, Wang Ximing, Chen Linglong
Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Department of Radiology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
Autism Res. 2023 Sep;16(9):1693-1706. doi: 10.1002/aur.2991. Epub 2023 Aug 10.
Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same-sex controls. Given its central role, altered structures and functions, and sex-dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex-related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8-14 years) and 72 typically developing controls (TCs) (36 females, 8-14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design. We also assessed brain-behavior relationships and the effects of age on EC. We found significant diagnosis-by-sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain-behavior correlations and significant effects of age on EC.
自闭症谱系障碍（ASD）在男性中显著居多，但这种性别差异背后的神经生物学基础仍不清楚。性别不连贯（GI）理论表明，ASD在神经方面比同性对照组更具双性特征。鉴于其核心作用、结构和功能的改变以及ASD中与性别相关的网络差异，包括中央执行网络（CEN）、默认模式网络（DMN）和突显网络（SN）的三重网络模型已成为表征这种性别差异的候选模型。在此，我们使用2×2协方差分析析因设计，测量了来自自闭症脑成像数据交换库5个站点的72名ASD儿童（36名女性，8 - 14岁）和72名发育正常的对照组（TCs）（36名女性，8 - 14岁）这三个网络内部及之间与性别相关的有效连接性（EC）差异。我们还评估了脑 - 行为关系以及年龄对EC的影响。我们发现EC存在显著的诊断 - 性别交互作用：患有ASD的女性在DMN内部以及SN和CEN之间的EC显著高于男性ASD患者。这种交互模式支持了GI理论，表明患有ASD的女性中观察到的较高EC反映了向男性TCs中显示的较高EC水平的转变（神经男性化），而患有ASD的男性中较低的EC反映了向女性TCs中显示的较低EC水平的转变（神经女性化）。我们还发现了显著的脑 - 行为相关性以及年龄对EC的显著影响。
