Developmental human brain connectome from fetal stage to early childhood

The human brain undergoes the most rapid maturation across the lifespan from the fetal stage through early childhood. Diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rs-fMRI) enable noninvasive mapping of the emerging brain structural and functional connections, which can subsequently be examined using various network-based analytic approaches to characterize how brain network topology evolves during development. Here, we review developmental connectome studies spanning mid-gestation to early childhood using dMRI and rs-fMRI. During this critical early period, unique and dynamic short- and long-range connectivity changes continually reshape the brain connectome. Structural and functional brain networks achieve highly efficient topological architectures in early life, with small-world organization emerging prenatally and adult-like hub distributions observed at birth. Importantly, early connectome development is characterized by a shift from segregation to integration, facilitated by initially faster growth of short-range connections followed by the later strengthening of long-range connections, and demonstrates a hierarchical axis from primary to higher-order regions. Structural connectome maturation is underpinned by the microstructural enhancement of certain white matter fibers and the pruning of others, while functional network emergence is supported by increased cerebral blood flow. Moreover, neurodevelopmental disorders such as autism and schizophrenia are associated with aberrant patterns of hyper- and hypo-connectivity, respectively, and exhibit atypical maturation of brain connectivity, underscoring the need for a developmental perspective. Collectively, this review outlines the spatiotemporal principles of early connectome development, discusses key challenges and methodological considerations in studying the baby brain connectome, setting the stage for understanding aberrant brain development during this vulnerable period.