Development of hippocampal subfield volumes from 4 to 22 years

Abstract

The hippocampus supports several important cognitive functions known to undergo substantial development during childhood and adolescence, for example, encoding and consolidation of vivid personal memories. However, diverging developmental effects on hippocampal volume have been observed across studies. It is possible that the inconsistent findings may attribute to varying developmental processes and functions related to different hippocampal subregions. Most studies to date have measured global hippocampal volume. We aimed to explore early hippocampal development both globally and regionally within subfields. Using cross-sectional 1.5 T magnetic resonance imaging data from 244 healthy participants aged 4-22 years, we performed automated hippocampal segmentation of seven subfield volumes; cornu ammonis (CA) 1, CA2/3, CA4/dentate gyrus (DG), presubiculum, subiculum, fimbria, and hippocampal fissure. For validation purposes, seven subjects were scanned at both 1.5 and 3 T, and all subfields except fimbria showed strong correlations across field strengths. Effects of age, left and right hemisphere, sex and their interactions were explored. Nonparametric local smoothing models (smoothing spline) were used to depict age-trajectories. Results suggested nonlinear age functions for most subfields where volume increases until 13-15 years, followed by little age-related changes during adolescence. Further, the results showed greater right than left hippocampal volumes that seemed to be augmenting in older age. Sex differences were also found for subfields; CA2/3, CA4/DG, presubiculum, subiculum, and CA1, mainly driven by participants under 13 years. These results provide a detailed characterization of hippocampal subfield development from early childhood.

Keywords: brain maturation; children; dentate gyrus; hippocampus; magnetic resonance imaging.

Figure 1

The figure shows the result of the hippocampus segmentation for one subject superimposed on the subject's T1‐weighted scan in sagittal, coronal, and axial views, respectively. Right column: Colour coded hippocampal subfield segmentation. The last volume labelled “hippo rest” is the tail of the hippocampus where the delineation no longer discerns between the different subfields. CA = cornu ammonis, DG = dentate gyrus, Fissure = hippocampal fissure.

Figure 2

Scatterplots showing hippocampal subfields and total hippocampal volume against age, with local smoothing models. Volume is reported in number of 0.5 mm³ voxels and age is shown in years. Fissure = hippocampal fissure. Total hippocampus = total hippocampal volume where all subfields, including the tail of the hippocampus, is added together.