Heritability and cross-species comparisons of human cortical functional organization asymmetry

Abstract

The human cerebral cortex is symmetrically organized along large-scale axes but also presents inter-hemispheric differences in structure and function. The quantified contralateral homologous difference, i.e., asymmetry, is a key feature of the human brain left-right axis supporting functional processes, such as language. Here, we assessed whether the asymmetry of cortical functional organization is heritable and phylogenetically conserved between humans and macaques. Our findings indicate asymmetric organization along an axis describing a functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization in humans. These asymmetries were heritable in humans and showed a similar spatial distribution with macaques, in the case of intra-hemispheric asymmetry of functional hierarchy. This suggests (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques. Overall, our findings suggest a genetic basis for asymmetry in intrinsic functional organization, linked to higher-order cognitive functions uniquely developed in humans.

A Comparative Perspective on the Cerebello-Cerebral System and Its Link to Cognition

“…Integrating multimodal, cross-species data in a standardized manner will enable the comparison of function-related, connectivity-dependent evolutionary variations across species [210]. Comparative neuroimaging methods are likely to contribute significantly to this endeavor [206,207,210], as illustrated by contemporary studies that compare macaques and chimpanzees to humans [6,[214][215][216]. Even without the ability to directly compare across species, the integration of evolutionary accounts with neuroimaging data [89,175,177] and insights into disease [197] allow for further exploration of cerebellar contributions to brain evolution and its associated function.…”

Diverging asymmetry of intrinsic functional organization in autism

“…Together, these gradients describe patterns of developmental and heritable variation in the human cortex (Dong et al, 2021;Valk et al, 2022;Xia et al, 2022). In previous work, we and others have shown robust hemispheric differences in functional organization in non-autistic adults (Gonzalez Alam et al, 2021;Liang et al, 2021;Wan et al, 2022). For example, the main lateralization axis separated different abstract cognitive functions (language to executive function) from left to right (Wan et al, 2022).…”

“…In previous work, we and others have shown robust hemispheric differences in functional organization in non-autistic adults (Gonzalez Alam et al, 2021;Liang et al, 2021;Wan et al, 2022). For example, the main lateralization axis separated different abstract cognitive functions (language to executive function) from left to right (Wan et al, 2022). Given that language impairments and verbal imbalances are key traits of autism (Boucher, 2012;Hong et al, 2023;Kjellmer et al, 2018;Vogindroukas et al, 2022) and executive function may underlie the psychological and behavioral neurodivergence observed in autism (Demetriou et al, 2018;Zhang et al, 2020), we hypothesize that atypical lateralization axes in autism may contribute to autistic behaviors.…”

“…To further understand system-level functional lateralization alterations in autism, here we investigated the asymmetry of intra-and inter-hemispheric functional connectome gradients (Gotts et al, 2013;Wan et al, 2022), which robustly capture associated organizational features (Margulies et al, 2016;Vos de Wael et al, 2020). Cortical regions show organizational axes reflecting integration and segregation (Gotts et al, 2013) along different dimensions (Huntenburg et al, 2018;Margulies et al, 2016;Paquola et al, 2022;Smallwood et al, 2021).…”

“…Because brain asymmetry (Kong et al, 2018;Roe et al, 2021) and gradients (Bethlehem et al, 2020;Dong et al, 2021;Xia et al, 2022) are affected by age, we also evaluated the interaction of age and autism status to reveal the cross-sectional developmental trajectory. Given the heritability of functional gradient asymmetry (Wan et al, 2022), and also of autism (Colvert et al, 2015;Tick et al, 2016), we used prior heritability estimates (Wan et al, 2022), to evaluate whether autism is associated with differences in regions found to be heritable in adulthood. Finally,…”