What structural and connectivity features of the human brain help to explain the extraordinary human cognitive abilities? We recently proposed a set of relevant connectomic fundamentals, some of which arise from the size scaling of the human brain relative to other primate brains, while others of these fundamentals may be uniquely human. In particular, we suggested that the remarkable increase of the size of the human brain due to its prolonged prenatal development has brought with it an increased sparsification, hierarchical modularization, as well as increased depth and cytoarchitectonic differentiation of brain networks. These characteristic features are complemented by a shift of projection origins to the upper layers of many cortical areas as well as the significantly prolonged postnatal development and plasticity of the upper cortical layers. Another fundamental aspect of cortical organization that has emerged in recent research is the alignment of diverse features of evolution, development, cytoarchitectonics, function, and plasticity along a principal, natural cortical axis from sensory (“outside”) to association (“inside”) areas. Here we highlight how this natural axis is integrated in the characteristic organization of the human brain. In particular, the human brain displays a developmental expansion of outside areas and a stretching of the natural axis such that outside areas are more widely separated from each other and from inside areas than in other species. We outline some functional implications of this characteristic arrangement. Author Summary Which brain connectivity features underlie the extraordinary human cognitive abilities? We have proposed a set of relevant connectomic fundamentals, including the increased sparsification, hierarchical modularization, as well as increased depth and cytoarchitectonic differentiation of cortical networks due to the prolonged prenatal development and size increase of the human brain. Such features are complemented by a shift of projection origins to the upper layers of many cortical areas and significantly prolonged postnatal development of such layers. Another fundamental aspect of cortical organization is the alignment of diverse features of evolution, development, cytoarchitectonics, function, and plasticity along a natural cortical axis from sensory (“outside”) to association (“inside”) areas. Here we highlight how this natural axis is integrated in the characteristic connectivity organization of the human brain.

The connections linking neurons within and between cerebral cortical areas form a multiscale network for communication. We review recent work relating essential features of cortico-cortical connections, such as their existence and laminar origins and terminations, to fundamental structural parameters of cortical areas, such as their distance, similarity in cytoarchitecture, defined by lamination or neuronal density, and other macroscopic and microscopic structural features. These analyses demonstrate the presence of an architectonic type principle. Across species and cortices, the essential features of cortico-cortical connections vary consistently and strongly with the cytoarchitectonic similarity of cortical areas. By contrast, in multivariate analyses such relations were not found consistently for distance, similarity of cortical thickness, or cellular morphology. Gradients of laminar cortical differentiation, as reflected in overall neuronal density, also correspond to regional variations of cellular features, forming a spatially ordered natural axis of concerted architectonic and connectional changes across the cortical sheet. The robustness of findings across mammalian brains allows cross-species predictions of the existence and laminar patterns of projections, including estimates for the human brain that are not yet available experimentally. The architectonic type principle integrates cortical connectivity and architecture across scales, with implications for computational explorations of cortical physiology and developmental mechanisms. Author Summary The mammalian cortex possesses multiple dimensions of organization, for instance, the connectional and the cytoarchitectonic dimension. Are there principles that link the different dimensions? Here we review an architectonic type principle that links cytoarchitectonic aspects of the cerebral cortex, such as neuron density or morphology across the cortical layers, to large-scale interregional cortical connection patterns. The reviewed findings highlight the existence of a natural axis of spatially ordered, concerted changes of multiple architectonic, connectional, and functional features stretching from less to more differentiated cortical areas. This framework comprises species-general, but also species-specific, principles of the organization of the mammalian, and particularly the primate, cerebral cortex and highlights potential developmental underpinnings as well as functional ramifications of such principles.