A key component of current theories of brain structure and function is the layer-specific origin of structural connections of the cerebral cortex. This fundamental connectional feature pertains to different mammalian cortices, and recent neuroimaging advancements have started to pave the way for its function-based mapping in humans. Here, we propose a framework that systematically explains the characteristic layer-specific origin of structural connections and its graded variation across the cortical sheet and across mammalian species. The framework unifies seemingly dispersed observations on multiple levels of cortical organization, including the cellular, connectional, and functional level. Moreover, the framework allows the prediction of the layer-specific origin of connections in a spectrum of mammals, from rodents to humans.
