Converging Topographic Axes of Connectivity and Genetic Architectures across the Cerebral Cortex

Genetic factors have involved the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogenous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles to reveal the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across the cortex. Instead of considering a complex one-to-one mapping between genetic coding and interareal connectivity, we hypothesized the existence of a more efficient way that the organizing principles are embedded in genetic profiles to underpin the cortical wiring space. Leveraging on the vertex-wise tractography in diffusion-weighted MRI, we derived the global connectopies to reliably index the organizing principles of interareal connectivityvariation in a low-dimensional space, which specifically captured three dominant topographic patterns along the dorsoventral, rostrocaudal, and mediolateral axes of the cortex. More importantly, we demonstrated that the global connectopies converge to the gradients of vertex-by-vertex genetic correlation matrix on the phenotype of cortical morphology and the cortex-wide spatiomolecular gradients. By diving into the genetic profiles, we found the critical role of genes related to brain morphogenesis in scaffolding the global connectopies. Taken together, our findings demonstrated the existence of a genetically determined space to encode the interareal connectivity variation, which may give new insights into the links between cortical connections and arealization. Teaser We identify a common space linking genetic profiling and interareal connectivity variation. ### Competing Interest Statement The authors have declared no competing interest.