Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex

Abstract

Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social-cognition and autobiographical memory. Our findings suggest that genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition.

Multiscale neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

“…This is in particular notable with respect to the heteromodal vs paralimbic anchor that these two gradients radiate towards. Mounting evidence suggests that heteromodal systems, such as the default mode network, decouple from microstructurally defined axes of brain organization that mainly describe differences in laminar differentiation 38 , 116 . That work has also shown that regions with strong microstructure-function decoupling also host more flexible cognitive functions, and have marked cross-species differences between humans and nonhuman primates.…”

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

“…To phylogenetically map the asymmetry of functional gradients across macaques and humans, we transformed the human gradients to macaque cortex surface based on a functional joint alignment technique ( Xu et al, 2020 ). This method leverages advances in representing functional organization in high-dimensional common space and provides a transformation between human and macaque cortices, also previously used in Valk et al, 2020 ; Valk et al, 2022 .…”

“…Gradients provide a synoptic framework to capture smooth variations of connectivity patterns across the cortical mantle. They describe variations in genetic patterning ( Vainik et al, 2020 ; Valk et al, 2020 ; Valk et al, 2022 , functional processes Margulies et al, 2016 ; Murphy et al, 2018 ; Turnbull et al, 2020 ), and are observed across species ( Valk et al, 2020 ; Coletta et al, 2020 ; Xu et al, 2020 ). Gradients have been linked to graph-theoretical markers such as degree centrality ( Hong et al, 2019 ) and microcircuit dynamics ( Park et al, 2021 ) as well as connectivity distance ( Hong et al, 2019 ; Wang et al, 2021 ).…”

Functional orderly topography of brain networks associated with gene expression heterogeneity

“…The multimodal association areas and their structural and functional connections in the human brain, primarily constituting cognitive functional networks, such as the frontoparietal network, salience network, and default-mode network, play an essential role in higher-order brain functions 10 – 12 . Most recent studies suggest that the development of higher-order cognitive networks in recent human brain evolution is associated with specific gene expression profiles 13 – 15 . The highly consistent transcriptional architecture in neocortex is correlated with resting-state functional connectivity 13 , and genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition 15 .…”

“…Most recent studies suggest that the development of higher-order cognitive networks in recent human brain evolution is associated with specific gene expression profiles 13 – 15 . The highly consistent transcriptional architecture in neocortex is correlated with resting-state functional connectivity 13 , and genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition 15 . However, the pattern of gene expression in the human brain to support the emergence of higher-order brain functions remains to be determined.…”