The effective connectome over a century of human life.

Brain functional connectomes describe the coordination principles of neural systems. Understanding normative developmental connectomes is crucial for standardized growth assessment and early disease detection. However, functional connectome has been mostly studied using undirected functional connectivity estimated based on statistical correlation of functional MRI (fMRI) signals. Effective connectivity (EC), in comparison, builds on a generative model of neural interactions and provides directed connectivity strengths among neural populations. To understand how EC evolves with age, we charted the lifespan effective connectome of human brain networks based on high-quality fMRI data from the Lifespan Human Connectome Projects. We found that global and network EC follows an overall inverted U-shape development with an average maturation time at around 9 years of age, significantly earlier than functional connectivity. Regional EC strength exhibits diverse evolution patterns and is more variable during early development than later life, underscoring a critical early window of plasticity. Also, maturation of excitatory and inhibitory nodal EC follows opposite hierarchical sequences. Moreover, the development of nodal EC is constrained by the sensorimotor-association (S-A) gradient, primarily governed by inhibitory EC. Our work reveals fundamental development principles of directed causal interactions between functional networks, offering a foundation for more precise and individualized brain assessments.