
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.19.608590
preprint
1
Article
The developing hippocampus: Microstructural evolution through childhood and adolescence
Karat Bradley G. http://orcid.org/0000-0002-6550-1418

Genc Sila http://orcid.org/0000-0002-4624-7071

Raven Erika P. http://orcid.org/0000-0002-9567-5259

Palombo Marco http://orcid.org/0000-0003-4892-7967

Khan Ali R. http://orcid.org/0000-0002-0760-8647

Jones Derek K. http://orcid.org/0000-0003-4409-8049

19 8 2024
2024.08.19.608590https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.08.19.608590
nihpp-2024.08.19.608590.pdf
Abstract

The hippocampus is a structure in the medial temporal lobe which serves multiple cognitive functions. While important, the development of the hippocampus in the formative period of childhood and adolescence has not been extensively investigated, with most contemporary research focusing on macrostructural measures of volume. Thus, there has been little research on the development of the micron-scale structures (i.e., microstructure) of the hippocampus, which engender its cognitive functions. The current study examined age-related changes of hippocampal microstructure using diffusion MRI data acquired with an ultra-strong gradient (300 mT/m) MRI scanner in a sample of children and adolescents (N=88; 8-19 years). Surface-based hippocampal modelling was combined with established microstructural approaches, such as Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion Density Imaging (NODDI), and a more advanced gray matter diffusion model Soma And Neurite Density Imaging (SANDI). No significant changes in macrostructural measures (volume, gyrification, and thickness) were found between 8-19 years, while significant changes in microstructure measures related to neurites (from NODDI and SANDI), soma (from SANDI), and mean diffusivity (from DTI) were found. In particular, there was a significant increase across age in neurite MR signal fraction and a significant decrease in extracellular MR signal fraction and mean diffusivity across the hippocampal subfields and long-axis. A significant negative correlation between age and MR apparent soma radius was found in the subiculum and CA1 throughout the anterior and body of the hippocampus. Further surface-based analyses uncovered variability in age-related microstructural changes between the subfields and long-axis, which may reflect ostensible developmental differences along these two axes. Finally, correlation of hippocampal surfaces representing age-related changes of microstructure with maps derived from histology allowed for postulation of the potential underlying microstructure that diffusion changes across age may be capturing. Overall, distinct neurite and soma developmental profiles in the human hippocampus during late childhood and adolescence are reported for the first time.
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pmc
