Genetic Effects on Structural and Functional Properties of Sensorimotor-Association Axis of Cortical Organization are Selectively Distinct

The topological differentiation of sensorimotor and association cortical regions along a sensorimotor-association (S-A) axis has undergone profound evolutionary change along the mammalian lineage. In humans, patterns of gene expression, microstructure, and functional connectivity have been shown to vary systematically along such S-A axis. Despite robust spatial relationships between these different neurobiological traits, whether common genetic pressures shape the S-A axis across traits remains poorly understood. In this study, we exploit observed pervasive inter-individual variation in the S-A axis to capture its genetic architecture and to study shared common genetic sources of structure-function relationships. To do so, we applied a structural equation modeling framework, which reduced the issue of measurement error heterogeneity across the cortex and its impact on structure-function relationship estimates. We then used genetic relatedness across pairs of twins and removed intra-individual differences to focus on the reliable inter-individual differences along the S-A functional axis. Notwithstanding robust spatial relationships and highly heritable inter-individual differences in S-A axis microstructure and functional organisation, and contrary to group-level findings, our results indicate distinct genetic effects across the different S-A axis properties. Together, our observations challenge the notion of a common genetic cause for the association between S-A axis structural and functional properties. Our approach highlights the diversity of genetic origins of brain features that co-vary along the S-A axis, which is key to interrogating inter-individual variability in brain organisation and its consequences on cognition. ### Competing Interest Statement The authors have declared no competing interest.