Effect of Gender on Development of Hippocampal Subregions From Childhood to Adulthood

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.

Keywords: MRI; development; gender; hippocampus; subregion.

Figure 1

Scatterplots of the ages of the females (red) and males (blue).

Figure 2

Scatterplots showing whole hippocampal volumes against age, using local smoothing models. Individual left (blue) and right (red) hippocampi are represented by individual lines. Volume is reported in mm³ and age is shown in years. L-Whole left whole hippocampus; R-Whole, the right whole hippocampus. *Indicates a significant relationship between volume and age after applying a 5% FDR correction.

Figure 3

Scatterplots showing the volumes of hippocampal subfields against age, using local smoothing models. Panel (A) is the left hippocampus and panel (B) is the right hippocampus. Individual hippocampal subregions are represented by individual lines. Volume is reported in mm³ and age is shown in years. L-Whole left whole hippocampus; R-Whole, the right whole hippocampus. *Indicates a significant relationship between volume and age after applying a 5% FDR correction.

Figure 4

Scatterplots showing the volumes of the hippocampal subfields against age in females and males, using local smoothing models. Panel (A) is the left hippocampus in females, panel (B) is the left hippocampus in males, panel (C) is the right hippocampus in females and panel (D) is the right hippocampus in males. Individual hippocampal subregions are represented by individual lines. Volume is reported in mm³ and age is shown in years. L, left; R, right. *Indicates a significant relationship of volume with age after applying a 5% FDR correction.

Figure 5

Comparison of the volumes of hippocampal subregions between the left (red circle) and right (blue triangle) hemispheres. *Indicates significant differences between left and right subfields after applying a 5% FDR correction.

Figure 6

Comparison of whole hippocampal volumes (left and right) between females (gray) and males (black). L, left; R, right. *Indicates significant differences between females and males uncorrected (P < 0.05).

Figure 7

Comparison of the volumes of hippocampal subregions (left and right) between females (gray) and males (black). Panels (A–L) showed hippocampal_tail, subiculum, CA1, hippocampal-fissure, presubiculum, parasubiculum, molecular layer HP, GC-ML-DG, CA3, CA4, fimbria and HATA, respectively. L, left; R, right. *Indicates significant differences between females and males uncorrected (P < 0.05).