Karat Bradley G, Genc Sila, Raven Erika P, Palombo Marco, Khan Ali R, Jones Derek K
Robarts Research Institute, Western University, London, ON, Canada.
Centre for Functional and Metabolic Mapping, Western University, London, ON, Canada.
bioRxiv. 2024 Aug 19:2024.08.19.608590. doi: 10.1101/2024.08.19.608590.
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.
海马体是内侧颞叶中的一种结构，具有多种认知功能。虽然海马体很重要，但在儿童期和青少年期的形成阶段，其发育情况尚未得到广泛研究，当代大多数研究都集中在体积的宏观结构测量上。因此，关于海马体微观尺度结构（即微结构）的发育研究很少，而正是这些微结构产生了其认知功能。本研究使用超强梯度（300 mT/m）MRI扫描仪采集的扩散MRI数据，对儿童和青少年样本（N = 88；8 - 19岁）中海马体微结构的年龄相关变化进行了研究。基于表面的海马体建模与既定的微结构方法相结合，如扩散张量成像（DTI）和神经突方向分散密度成像（NODDI），以及一种更先进的灰质扩散模型——体细胞和神经突密度成像（SANDI）。在8 - 19岁之间，未发现宏观结构测量指标（体积、脑回形成和厚度）有显著变化，而在与神经突（来自NODDI和SANDI）、体细胞（来自SANDI）和平均扩散率（来自DTI）相关的微结构测量指标上发现了显著变化。特别是，神经突MR信号分数随年龄显著增加，细胞外MR信号分数和平均扩散率在海马体亚区和长轴上显著降低。在海马体前部和体部的整个下托和CA1区域，发现年龄与MR表观体细胞半径之间存在显著负相关。进一步基于表面的分析揭示了亚区和长轴之间与年龄相关的微结构变化的变异性，这可能反映了沿这两个轴表面上的发育差异。最后，将代表微结构年龄相关变化的海马体表与组织学图谱进行相关性分析，有助于推测扩散随年龄变化可能捕捉到的潜在微结构。总体而言，首次报告了人类海马体在儿童晚期和青少年期独特的神经突和体细胞发育特征。
