Extreme male developmental trajectories of homotopic brain connectivity in autism

Abstract

It has been proposed that autism spectrum disorder (ASD) may be characterized by an extreme male brain (EMB) pattern of brain development. Here, we performed the first investigation of how age‐related changes in functional brain connectivity may be expressed differently in females and males with ASD. We analyzed resting‐state functional magnetic resonance imaging data of 107 typically developing (TD) females, 114 TD males, 104 females, and 115 males with ASD (6–26 years) from the autism brain imaging data exchange repository. We explored how interhemispheric homotopic connectivity and its maturational curvatures change across groups. Differences between ASD and TD and between females and males with ASD were observed for the rate of changes in connectivity in the absence of overall differences in connectivity. The largest portion of variance in age‐related changes in connectivity was described through similarities between TD males, ASD males, and ASD females, in contrast to TD females. We found that shape of developmental curvature is associated with symptomatology in both males and females with ASD. We demonstrated that females and males with ASD tended to follow the male pattern of developmental changes in interhemispheric connectivity, supporting the EMB theory of ASD.

Enhancement of indirect functional connections with shortest path length in the adult autistic brain

“…Using seed-based and whole-brain functional connectivity analyses, Alaerts et al (2016) found that autistic males predominantly displayed hypo-connectivity while autistic females predominantly exhibited hyper-connectivity compared to sex-matched typical controls. Interhemispheric homotopic functional connectivity was showed to follow different development trajectories between autistic males and females (Kozhemiako et al, 2019). In the current study, failure to detect a diagnosis-by-sex interaction effect on global SMP (Table 2) suggests sex-independent semi-metric changes in autistic adults, although small sample sizes reduce statistical power.…”

“…(a) Post-hoc analyses for main effect of sex on SMP. Interhemispheric homotopic functional connectivity was showed to follow different development trajectories between autistic males and females (Kozhemiako et al, 2019). (b) Main effect of sex at the network level.…”

“…The question arises whether the brain functional organization differs between autistic males and females after taking typical sex differences into account. To the best of our knowledge, only three studies have assessed resting-state functional connectivity in autistic males and females (Alaerts, Swinnen, & Wenderoth, 2016;Di & Biswal, 2016;Kozhemiako et al, 2019).…”

Altered inter‐ and intrahemispheric functional connectivity dynamics in autistic children

“…The current study included only male children due to the relatively limited number of female participants in ABIDE database. Yet, there is considerable evidence that biological sex contributes to the heterogeneity of ASD on functional connectivity (Alaerts, Swinnen, & Wenderoth, 2016;Kozhemiako et al, 2019), neuroanatomy (Lai et al, 2013) and genetics (Jeste & Geschwind, 2014). How sex heterogeneity interacts with intra-and interhemispheric functional connectivity dynamics should be addressed in future studies to advance our understanding the sex differences in ASD.…”

“…However, our understanding of the intrahemispheric and interhemispheric functional processing in ASD remains relatively limited (Anderson et al, 2011;Di Martino et al, 2014;Dinstein et al, 2011;Hahamy, Behrmann, & Malach, 2015;Kozhemiako et al, 2019;Lee, Kyeong, Kim, & Cheon, 2016). Notably, most of these studies have focused on the interhemispheric functional connectivity by evaluating the neural synchronization between homologous voxels and showed consistently reduced interhemispheric connections in ASD (Anderson et al, 2011;Di Martino et al, 2014;Dinstein et al, 2011;Kozhemiako et al, 2019). To the best of our knowledge, only two fMRI studies have investigated both intra-and interhemispheric functional connectivity at rest in ASD (Hahamy et al, 2015;Lee et al, 2016).…”