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 age-related trajectories, which were coupled with cortical functional hierarchy, most prominently within the frontoparietal and ventral-attention / action-mode systems. These gradients showed distinct associations with episodic memory and specific aspects of executive function. The hippocampus showed age-related decreases in the coupling between geometric modes and functional gradients. 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 and their associations with cortical hierarchy and cognitive maturation, offering a parsimonious framework for developmental neuroscience.