Functional Orderly Topography of Brain Networks Associated with Gene Expression Heterogeneity

The human cerebral cortex expanded much more relative to non-human primates and rodent in evolution, leading to a functional orderly topography of the brain networks. Here, we show that functional topography may be associated with gene expression heterogeneity in various brain structures. The neocortex exhibits greater gene expression heterogeneity, with lower housekeeping gene proportion, a longer mean path length, less clusters, and a lower degree of ordering of networks, compared to archicortical and subcortical area in human, rhesus macaque, and mouse brains consistently. In particular, the cerebellar cortex displays greater gene expression heterogeneity than cerebellar deep nuclei in the human brain, but not in the mouse brain, corresponding to the emergence of novel functions in the human cerebellar cortex. Moreover, the cortical areas with greater gene expression heterogeneity, primarily located in multimodal association cortex, tend to express genes with higher evolutionary rates and exhibit higher functional connectivity degree measured by resting-state fMRI, implying that such spatial pattern of cortical gene expression may be shaped by evolution and favorable for the specialization of higher cognitive functions. Together, the cross-species imaging genetic findings may provide convergent evidence to support the association between the orderly topography of brain function networks and gene expression.