Gene Gradients Reveal Directed Structural Connectivity Across Species

Diffusion MRI (dMRI) tractography is widely used to estimate structural connectivity (SC) between brain regions in vivo, but it cannot determine the direction of white matter pathways. Here, we introduce a structure-function computational model that combines dMRI-derived SC, gene co-expression gradients, and functional activity data to infer structural directionality. Our model accurately predicts ground truth directionality in C. elegans (r=0.70), mouse (r=0.57), and macaque (r=0.46). We then inferred directionality across 770 healthy young adults from the Human Connectome Project. Predicted directionality reproduced established asymmetries between the primary sensory areas and the thalamus