Cortical microarchitecture supports preadolescent functional brain network connectivity

Abstract

A century ago, Brodmann suggested that local cortical microarchitecture dictates function, yet modern structure-function mapping overwhelmingly focuses on white matter macroarchitecture. Here, we reframe structure-function coupling by linking gray matter microarchitecture and macroscale connectomics, demonstrating how gray matter cellular and neurite density are linked to functional network organization in preadolescents. By applying partial least squares correlation to cortical microarchitecture (i.e., cellular and neurite density) estimates from diffusion MRI and network connectivity estimates from functional MRI, in 6,320 children ages 9-11 years from the U.S.-wide Adolescent Brain Cognitive Development (ABCD) Study, we identified several principles of structure-function coupling. First, we found that functional connectivity is associated with one dominant and global pattern of cellular density differences explaining nearly 80% of shared variance, but by several patterns of neurite density differences. Second, we found similar gradients of sensorimotor network connectivity related to this dominant cellular density pattern and the secondary, rostro-caudal neurite density pattern (explaining 17% of shared variance). Third, we found a profile of attention network connectivity associated with the primary neurite density pattern (44% of shared variance) and the secondary, rostro-caudal cellular density pattern (5% of shared variance). Altogether, this work suggests that cellular density (i.e., neuronal cell bodies, support cells) across cortex largely supports a sensorimotor network connectivity gradient. Conversely, there are several connectivity-related patterns of neurite density (i.e., axons, dendrites) across cortex, providing a glimpse into how local neurite connectivity may differentially support long-range functional connectivity of sensorimotor networks and attention networks.