Abstract
The hippocampus plays a crucial role in cognition, yet its microstructural development during childhood and adolescence remains poorly understood. Here, we investigate age-related differences in hippocampal microstructure using diffusion MRI with ultra-strong gradients (300 mT/m) in a cohort of 88 participants aged 8–19 years. Surface-based hippocampal modelling was combined with established microstructural approaches, and a more advanced biophysical model (Soma and Neurite Density Imaging: SANDI) suited for studying cortical microstructure. Hippocampal volume, gyrification, and thickness remained stable across this developmental window, however we observed significant differences across age related to MR-derived neurite and soma parameters. Diffusion-derived changes across age were found to be correlated with adult microstructure maps related to myelin and iron content, synaptic density, and hippocampal interneurons derived from MRI, PET and histology. These findings highlight age-related differences of MR-derived neurite and soma parameters in the human hippocampus during late childhood and adolescence, offering insights into structural maturation during this critical period.
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Data availability
The histology, ex vivo MRI, and PET maps can be found in both the HippoMaps (osf.io/92p34/) and NeuroMaps (https://github.com/netneurolab/neuromaps) toolbox. Due to the inclusion of minors (under 18 participants), the availability of derived or identifiable data from the participant cohort is restricted due to privacy concerns. Derived data supporting the findings of the imaging analyses are available by contacting the authors in writing via email, allowing 4 weeks for access requests to be granted. Numerical Source data underlying all graphs in this article can be found in the Supplementary data file.
Code availability
The SANDI model was fit to the diffusion data using an open-source MATLAB toolbox (https://github.com/palombom/SANDI-Matlab-Toolbox-v1.0). Code to repeat the study analyses can be found at: https://doi.org/10.17605/OSF.IO/4AQXR.
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Acknowledgements
The data were acquired at the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, funded by the EPSRC (grant EP/M029778/1) and The Wolfson Foundation. B.G.K. is supported by a post-graduate scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). S.G. is supported by the Royal Children’s Hospital Foundation (RCHF 2022-1402). E.P.R. is supported by NICHD at NIH (F32HD103313). M.P. is funded by UKRI Future Leaders Fellowship (MR/T020296/2). A.R.K. is supported by the Canada Research Chairs program #950-231964, NSERC Discovery Grants RGPIN-2015-06639 and RGPIN-2023-05558, Canadian Institutes for Health Research Project grant #366062, Canada Foundation for Innovation (CFI) John R. Evans Leaders Fund project #37427, the Canada First Research Excellence Fund, and Brain Canada. D.K.J. is supported by a Wellcome Trust Investigator Award (096646/Z/11/Z) and a Wellcome Trust Strategic Award (104943/Z/14/Z). We thank the children/adolescents (and their carers) for generously donating their time to participate in this study.
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S.G. and E.P.R. acquired the data with input from M.P. and D.K.J.; B.G.K. devised the study methods and analysis; B.G.K. performed the analysis and wrote the code; S.G., E.P.R., M.P., A.R.K., and D.K.J. refined the analysis; B.G.K. wrote the manuscript; S.G., E.P.R., M.P., A.R.K., and D.K.J. edited the manuscript; All authors commented on and discussed the results.
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Karat, B.G., Genc, S., Raven, E.P. et al. Microstructural variation of hippocampal substructures across childhood and adolescence quantified with high-gradient diffusion MRI. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09622-x
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DOI: https://doi.org/10.1038/s42003-026-09622-x
