Deciphering developmental gradients in human hippocampus

The cortical organization of human hippocampus is multidimensional, yet its developmental profile and underlying mechanisms remain largely unknown. We combined three large-scale developmental cohorts to conduct a multiscale association study and revealed a reproducible triple-gradient organization profile on the hippocampus with distinct brain-mind maturational profiles. This multidimensional organization uniquely shapes the development of cortical hierarchy, most prominently within the frontoparietal (cognitive control) and cingulo-opercular (action mode) systems. Specifically, the three gradients differentially support maturation of episodic memory and specific aspects of executive function. A progressive relaxation of geometric constraints of human hippocampus was detectable on its function over development while this mirrors regional myelination patterns related to maturation of hippocampal gradients. Further transcriptome analyses find a link between these gradient reorganization and molecular pathways underlying neurodevelopment, stress-hormone regulation, and neuroactive signaling. This multidimensional principle on hippocampal gradient organization may offer insights of its integrative growth with connectomic, geometric, myeloarchitectural, and transcriptomic factors to orchestrate the cortical hierarchy and cognitive maturation, forming a parsimonious framework for developmental neuroscience and brain health.