Structure-Function Coupling Aligns with a Unimodal-to-Transmodal Gradient in the Mouse Cortex

Abstract Understanding how anatomical connectivity shapes brain activity is essential for clarifying brain function and disorders. In the human brain, the regional heterogeneity in structure-function (S-F) coupling is well characterized by measuring correlations between structural and functional connectivity. However, it remains unclear whether the same principles apply to the mouse cortex, where biological mechanisms can be studied directly. Here, we mapped S-F coupling across the mouse cortex by combining high-resolution structural connectivity derived from axonal tracing with resting-state functional connectivity measured by wide-field calcium imaging. Our findings revealed that structural connectivity imposes a robust yet regionally variable constraint on functional connectivity. As in humans, the S-F coupling was strong in primary sensorimotor areas and weaker in association areas, demonstrating a gradient from unimodal-to-transmodal cortical organization. This spatial variation covaried with intrinsic cellular properties, including myelination, excitation-inhibition balance, synaptic density, and gene expression profiles, but did not align with the anatomically defined cortical hierarchy. Our findings highlight graded S-F coupling as a common organizational principle in both the mouse and human cortex, providing a framework for future mechanistic studies using mouse models. Competing Interest Statement The authors have declared no competing interest.