The Ontogeny of the Human Connectome

The human brain comprises distributed cortical regions that are structurally and functionally connected into a network that is known as the human connectome. Elaborate developmental processes starting in utero herald connectome genesis, with dynamic changes in its architecture continuing throughout life. Connectome changes during development, maturation, and aging may be governed by a set of biological rules or algorithms, forming and shaping the macroscopic architecture of the brain's wiring network. To explore the presence of developmental patterns indicative of such rules, this review considers insights from studies on the cellular and the systems level into macroscopic connectome genesis and dynamics across the life span. We observe that in parallel with synaptogenesis, macroscopic connectome formation and transformation is characterized by an initial overgrowth and subsequent elimination of cortico-cortical axonal projections. Furthermore, dynamic changes in connectome organization throughout the life span are suggested to follow an inverted U-shaped pattern, with an increasingly integrated topology during development, a plateau lasting for the majority of adulthood and an increasingly localized topology in late life. Elucidating developmental patterns in brain connectivity is crucial for our understanding of the human connectome and how it may give rise to brain function, including the occurrence of brain network disorders across the life span.