Correlated gene expression and anatomical communication support synchronized brain activity in the mouse functional connectome

Abstract Cognition and behavior depend on synchronized intrinsic brain activity which is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity in the mouse brain by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting state functional connectivity MRI. The model suggests that functional connectivity arises from synergies between anatomical links and inter-areal similarities in gene expression. By estimating these interactions, we identify anatomical modules in which correlated gene expression and anatomical connectivity cooperatively, versus distinctly, support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI.