Surface Expansion Regionalization of the Hippocampus in Early Brain Development

Abstract

The hippocampal formation is implicated in a myriad of crucial functions, particularly centered around memory and emotion, with distinct subdivisions fulfilling specific roles. However, there is no consensus on the spatial organization of these subdivisions, given that the functional connectivity and gene expression-based parcellation along its longitudinal axis differs from the histology-based parcellation along its medial-lateral axis. The dynamic nonuniform surface expansion of the hippocampus during early development reflects the underlying changes of microstructure and functional connectivity, providing important clues on hippocampal subdivisions. Moreover, the thin and convoluted properties bring out the hippocampal maturity largely in the form of expanding surface area. We thus unprecedentedly explore the development-based surface area regionalization and patterns of the hippocampus by leveraging 513 high-quality longitudinal MRI scans during the first two postnatal years. Our findings imply two discrete hippocampal developmental patterns, featuring one pattern of subdivisions along the anterior-posterior axis (head, regions 1 and 5; body, regions 2, 4, 6, and 7; tail, region 3) and the other one along the medial-lateral axis (subiculum, regions 4, 5, and 6; CA fields, regions 1, 2, and 7). Most of the resulting 7 subdivisions exhibit region-specific and nonlinear spatiotemporal surface area expansion patterns with an initial high growth, followed by a transition to low increase. Each subregion displays bilaterally symmetric pattern. The medial portion of the hippocampal head experiences the most rapid surface area expansion. These results provide important references for exploring the fine-grained organization and development of the hippocampus and its intricate cognitions.

Keywords: Developmental trajectory; Infant hippocampus; MRI; Surface area.

Fig. 1.. Determine the optimal subregion number r in bilateral hippocampi.

(A) and (B) correspond to the average silhouette coefficients and reconstruction errors across varying subregion numbers in left hippocampus. (C) and (D) pertain to the average silhouette coefficients and reconstruction errors in right hippocampus. The arrows denote the appropriate subregion number with local relatively high silhouette coefficients and low reconstruction errors.

Fig. 2.. The developmental regionalization maps of surface area.

Panels (A), (B), and (C) showcase the hippocampal parcellation maps with different region numbers (r = 2, 5, and 7) in bilateral hippocampi. (D) The spatial position of hippocampus relative to the brain. The coloring in D corresponds to C (r = 7).

Fig. 3.. Organization among the hippocampal subregions.

The dendrogram of the hierarchical relationship (A) among the hippocampal subregions using the Ward D2 method and the visualization upon grouping these regions into three distinct classes (B).

Fig. 4.. The longitudinal developmental trajectories of hippocampal absolute surface area.

(A) and (B) separately depict the surface area developmental pattern of each subregion in left and right hippocampi. The solid red and blue curves illustrate the population-fitted trajectories of each hippocampal subregion for females and males, respectively. The bule and red faint lines represent the developmental trajectories of each subject with multiple scans for males and females, respectively. The shaded ribbons represent 95% confidence intervals of the fitted curves. The brown horizontal bars on the X-axis mark the age intervals with significant sex differences.

Fig. 5.. The normalized surface area and the surface area expansion velocity.

(A) and (B) respectively showcase the normalized surface area relative to the surface area at birth and the monthly expansion velocity of the surface area in each hippocampal subregion at time points 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 months.

Fig. 6.. The longitudinal developmental trajectories of hippocampal relative surface area.

(A) and (B) separately delineate the surface area developmental pattern of each subregion in left and right hippocampi. The solid red and blue curves depict the population-fitted trajectories in each hippocampal subregion for females and males, respectively. The blue and red faint lines represent individual subject-specific surface area developmental trajectories, for males and females, respectively. The shaded ribbons represent 95% confidence intervals of the fitted curves. The brown horizontal bars on the X-axis delineate the age intervals with notable sex differences.