Sex differentiation of brain structures in autism: Findings from a gray matter asymmetry study

Abstract

Autism spectrum disorder (ASD) is diagnosed much more often in males than females. This male predominance has prompted a number of studies to examine how sex differences are related to the neural expression of ASD. Different theories, such as the “extreme male brain” theory, the “female protective effect” (FPE) theory, and the gender incoherence (GI) theory, provide different explanations for the mixed findings of sex‐related neural expression of ASD. This study sought to clarify whether either theory applies to the brain structure in individuals with ASD by analyzing a selective high‐quality data subset from an open data resource (Autism Brain Imaging Data Exchange I and II) including 35 males/35 females with ASD and 86 male/86 female typical‐controls (TCs). We examined the sex‐related changes in ASD in gray matter asymmetry measures (i.e., asymmetry index, AI) derived from voxel‐based morphometry using a 2 (diagnosis: ASD vs. TC) × 2 (sex: female vs. male) factorial design. A diagnosis‐by‐sex interaction effect was identified in the planum temporale/Heschl's gyrus: (i) compared to females, males exhibited decreased AI (indicating more leftward brain asymmetry) in the TC group, whereas AI was greater (indicating less leftward brain asymmetry) for males than for females in the ASD group; and (ii) females with ASD showed reduced AI (indicating more leftward brain asymmetry) compared to female TCs, whereas there were no differences between ASDs and TCs in the male group. This interaction pattern supports the FPE theory in showing greater brain structure changes (masculinization) in females with ASD. Lay Summary To understand the neural mechanisms underlying male predominance in autism spectrum disorder (ASD), we investigated the sex differences in ASD‐related alterations in brain asymmetry. We found greater changes in females with ASD compared with males with ASD, revealing a female protective effect. These findings provide novel insights into the neurobiology of sex differences in ASD.

Sex differences of the triple network model in children with autism: A resting‐state fMRI investigation of effective connectivity

“…reflected a shift towards the higher level of EC displayed in male TCs and the lower EC in males with ASD reflected a shift towards the lower level of EC displayed in female TCs. Thus, the EC changes were in line with the neural masculinization effect as proposed by the EMB theory (Deng & Wang, 2021) only in females with ASD, whereas the EC changes in males with ASD were consistent with the shift-towards-feminization (neural feminization) effect as proposed by the GI theory (Bejerot et al, 2012). Similar neural feminization patterns in males with ASD and neural masculinization patterns in females with ASD have been previously identified in neuroanatomical and FC studies (Alaerts et al, 2016).…”

A Multi-Site Anti-Interference Neural Network for ASD Classification

“…Brain regions of great relative importance in the two structures include vermis, frontal lobe, posterior cingulate gyrus, orbital part, fusiform gyrus, thalamus, temporal transverse gyrus, precuneus, horny gyrus, caudate nucleus, and hippocampus. These brain regions are the same as those reported in the literature for differences between ASD and TD [7,[27][28][29][30][31][32]. This indicates that the representation learning module can actively identify the brain regions that change due to disease, and extract the difference features for classification.…”

Gray matter asymmetry atypical patterns in subgrouping minors with autism based on core symptoms

“…In all general linear models and multiple regression analyses, the results were corrected for multiple comparisons using the Gaussian random field (GRF) procedure with the voxel level of P -value < 0.005 and the cluster level of P < 0.05 implemented by DPARSF ( Deng and Wang, 2021 ).…”