Abstract
The hippocampus is known to be comprised of several subfields, but the developmental trajectories of these subfields are under debate. In this study, we analyzed magnetic resonance imaging (MRI) data from a cross-sectional sample (198 healthy Chinese) using an automated segmentation tool to delineate the development of the hippocampal subregions from 6 to 26 years of age. We also examined whether gender and hemispheric differences influence the development of these subregions. For the whole hippocampus, the trajectory of development was observed to be an inverse-u. A significant increase in volume with age was found for most of the subregions, except for the L/R-parasubiculum, L/R-fimbria, and L-HATA. Gender-related differences were also found in the development of most subregions, especially for the hippocampal tail, CA1, molecular layer HP, GC-DG, CA3, and CA4, which showed a consistent increase in females and an early increase followed by a decrease in males. A comparison of the average volumes showed that the right whole hippocampus was significantly larger, along with the R-presubiculum, R-hippocampal-fissure, L/R-CA1, and L/R-molecular layer HP in males in comparison to females. Additionally, the average volume of the right hemisphere was shown to be significantly larger for the hippocampal tail, CA1, molecular layer HP, GC-DG, CA3, and CA4. However, for the presubiculum, parasubiculum, and fimbria, the left side was shown to be larger. In conclusion, the hippocampal subregions appear to develop in various ways from childhood to adulthood, with both gender and hemispheric differences affecting their development.
Highlights
The hippocampal cortex is an important structure in the limbic system, plays a critical role in memory, and is vulnerable to the effects of aging (Richter-Levin, 2004; Malykhin et al, 2017; Zammit et al, 2017)
Positive associations between age and volume are observed bilaterally for the whole hippocampus from 6 to 26 years of age (P < 0.001 for both left and right). For both of these volumes, the trajectory of their development was observed to be an inverse-u, in which the volume was shown to increase early, followed by slight decreases (Figure 2). Among these studies of the hippocampal subregions, our results showed significant corrected (P = 0.002 for L-CA3, P < 0.001 for the others) age-related volume increases for all of the subregions, except the L/R-parasubiculum, L/R-fimbria, and L-HATA (Figure 3)
Three important findings can be drawn from the results of this study: (1) For the whole hippocampus, the development of both the left and right hemispheres followed an inverted U-shaped trajectory from 6 to 26 years of age, the hippocampal subregions showed heterogeneous developmental patterns, with significant age-related volume increases for all subregions except for the L/R-parasubiculum, L/R-fimbria, and L-HATA; (2) the development of the hippocampal subregions showed sexual dimorphism from 6 to 26 years of age, showing a consistent increase in females and an early increase followed by a decrease in males for most subregions; and (3) the average volume of the hippocampal subregions between 6–26 years of age showed both gender and hemisphere related differences
Summary
The hippocampal cortex is an important structure in the limbic system, plays a critical role in memory, and is vulnerable to the effects of aging (Richter-Levin, 2004; Malykhin et al, 2017; Zammit et al, 2017). The hippocampus formation is not a homogeneous structure and is comprised of several subfields with distinctive histological characteristics, including the subiculum (which can be further subdivided into the pre-subiculum, parasubiculum, and the subiculum proper), the four cornu ammonis sectors (CA1–4), and the dentate gyrus (Duvernoy, 2005). These subfields have been shown to play different roles in memory and learning (Yassa and Stark, 2011; Kesner, 2013; Reagh et al, 2014), and subsequently, are affected differently by Alzheimer’s disease (AD) and the normal process of aging. We utilized the more detailed segmentation method proposed by Iglesias et al (2015) and examined the parasubiculum, presubiculum, subiculum, CA1, CA3, CA4, GC-DG, HATA, fimbria, molecular layer HP, fissure, and the tail in both the left and right hippocampus
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