Developmental Landscape of Gradients in Human Hippocampus

Understanding hippocampal–cortical integration is critical for cognitive development, yet the hippocampus’ multidimensional organization and its developmental coupling with cortical systems during youth remain unclear. Here, across three large-scale developmental cohorts, we conducted a multiscale association study that revealed reproducible triple-gradient organizations of the hippocampus and their distinct maturational trajectories, which uniquely shape cortical hierarchy, most prominently within the frontoparietal and ventral-attention or action-mode systems. These gradients differentially support episodic memory and specific aspects of executive function. Mechanistically, the hippocampus exhibits a progressive relaxation of geometric constraints on its function over development. Furthermore, the maturation of hippocampal gradients mirrors regional myelination patterns, while transcriptome analyses link gradient reorganization to molecular pathways of neurodevelopment, stress-hormone regulation, and neuroactive signaling. These findings demonstrate a developmental landscape of the triple gradients in human hippocampus to orchestrate cortical hierarchy and cognitive maturation, offering a parsimonious framework for developmental neuroscience.