Diverging asymmetry of intrinsic functional organization in autism

Abstract

Autism is a neurodevelopmental condition involving atypical sensory-perceptual functions together with language and socio-cognitive deficits. Previous work has reported subtle alterations in the asymmetry of brain structure and reduced laterality of functional activation in individuals with autism relative to non-autistic individuals (NAI). However, whether functional asymmetries show altered intrinsic systematic organization in autism remains unclear. Here, we examined inter- and intra-hemispheric asymmetry of intrinsic functional gradients capturing connectome organization along three axes, stretching between sensory-default, somatomotor-visual, and default-multiple demand networks, to study system-level hemispheric imbalances in autism. We observed decreased leftward functional asymmetry of language network organization in individuals with autism, relative to NAI. Whereas language network asymmetry varied across age groups in NAI, this was not the case in autism, suggesting atypical functional laterality in autism may result from altered developmental trajectories. Finally, we observed that intra- but not inter-hemispheric features were predictive of the severity of autistic traits. Our findings illustrate how regional and patterned functional lateralization is altered in autism at the system level. Such differences may be rooted in atypical developmental trajectories of functional organization asymmetry in autism.

Altered asymmetry of functional connectome gradients in major depressive disorder

“…Despite the overall similar gradient patterns between the two hemispheres, we found that both MDD and healthy participants exhibited significant left-right differences, with each hemisphere showing relative advantages in particular functional modules. For example, we observed the leftward principal gradient in language-related regions, which has also been consistently observed in previous studies (Liang et al, 2021 ; Wan et al, 2022 , 2023 ), indicates higher integration of language and transmodal regions in the left hemisphere than in the right hemisphere. In contrast, we found that visual cortices exhibited rightward asymmetry, which may be related to previously reported right dominance of visuospatial function (Fink et al, 2001 ).…”

“…Figure 1A illustrated the average intra-hemispheric patterns of the first three gradients across all individuals. Consistent with previous literature (Margulies et al, 2016 ; Wan et al, 2022 , 2023 ), the principle gradient (G1) of both hemispheres capture a hierarchical organization where unimodal regions (e.g., visual and somatomotor networks) and transmodal regions (e.g., default mode network) were situated at opposite ends. The second gradient component (G2) reveals a hierarchy traversing from visual regions to somatosensory regions.…”

“…For network-level analyzes, we aggregated the AI scores of regions by Yeo's seven functional systems (Yeo et al, 2011 ), which included default mode, limbic, control, salience, dorsal attention, somatomotor, and visual networks. In line with previous work (Wan et al, 2023 ), the MDD-HC comparisons were conducted using a multivariate linear model whose dependent variable consisted of AI patterns along G1, G2, and G3. Age, sex, and head motion (mean FD) were entered as covariates in the model.…”

Microstructural asymmetry in the human cortex

“…Such a principle would be in line with the structural model, posing that regions with similar microstructure may be functionally connected (García-Cabezas et al, 2019). Indeed, various studies have demonstrated asymmetry along this sensory-transmodal-axis for intrinsic function (Gonzalez Alam et al, 2022; Labache et al, 2023; Liang et al, 2021; Wan et al, 2022, 2023).…”

The universe is asymmetric, the mouse brain too

“…For instance, in the striatum, we report a rightward bias in the caudoputamen volumes, while there is a leftward bias for the putamen in humans. Beyond looking at structural markers, there is also evidence for functional asymmetries, including in autism spectrum disorders, for instance using functional gradients 44 , that would be interesting to investigate in corresponding animal models 45,46 . This could unlock additional comparisons between species and help to bring an understanding of functional asymmetries.…”