Correlation Between Cortical Gene Expression And Resting State Functional Connectivity Strength In Healthy Young Adults

Background: Resting-state functional connectivity in the human brain is heritable;however,gene expression associated with functional connectivity strength(FCS)is still largely unknown.In this exploratory study,we aimed to answer three questions:(1)which genes are associated with FCS;(2)what are the biological functions of these genes? and(3)in which cell types and developmental periods are these genes overrepresented? Methods: We performed a comprehensive transcriptome-neuroimaging association investigation to identify the molecular correlates of whole-brain voxel-wise FCS rather than region-based functional connectivity.The FCS of each voxel in the whole cerebral cortex was computed in 100 healthy young adults from the Human Connectome Project.The FCS matrix was anatomically matched to the cortical gene expression matrix from the Allen Human Brain Atlas.A multivariate technique of partial least squares regression(PLSR)was then conducted to identify genes whose spatial expression profiles best predicted the FCS distribution.Validations were performed with different preprocessing methods for neuroimaging and gene expression data and with an independent imaging dataset.A suite of gene functional annotation tools was used to interpret the biological functions of FCS-related genes.Results: The regions with higher FCS values were predominantly located in the default mode network(DMN)[mainly involving the posterior cingulate cortex/precuneus(PCC/PCU),inferior parietal lobule,medial prefrontal cortex] and dorsolateral prefrontal cortex(DLPFC),lateral temporal,parietal and visual cortices,which is highly in line with the findings of the previous investigations.We found that FCS spatial distribution was significantly positively correlated with the expression of genes defined by the first PLSR component.The FCS-related genes we identified were significantly enriched for ion channels,axon guidance and synaptic transmission.Moreover,FCS-related genes were preferentially expressed in cortical neurons and in the young adulthood and were enriched in a number of neurodegenerative and neuropsychiatric disorders.The high level of overlap in the FCS-related genes using the different methods and the highly similar results across the two imaging datasets indicates the robustness of our study.Conclusions: Our results suggest that the spatial distribution of FCS in the human cerebral cortex is modulated by the expression of a set of genes associated with ion channels,axon guidance and synaptic transmission.