Hippocampal anterior- posterior shift in childhood and adolescence

Abstract

Hippocampal-cortical networks play an important role in neurocognitive development. Applying the method of Connectivity-Based Parcellation (CBP) on hippocampal-cortical structural covariance (SC) networks computed from T1-weighted magnetic resonance images, we examined how the hippocampus differentiates into subregions during childhood and adolescence (N = 1105, 6-18 years). In late childhood, the hippocampus mainly differentiated along the anterior-posterior axis similar to previous reported functional differentiation patterns of the hippocampus. In contrast, in adolescence a differentiation along the medial-lateral axis was evident, reminiscent of the cytoarchitectonic division into cornu ammonis and subiculum. Further meta-analytical characterization of hippocampal subregions in terms of related structural co-maturation networks, behavioural and gene profiling suggested that the hippocampal head is related to higher order functions (e.g. language, theory of mind, autobiographical memory) in late childhood morphologically co-varying with almost the whole brain. In early adolescence but not in childhood, posterior subicular SC networks were associated with action-oriented and reward systems. The findings point to late childhood as an important developmental period for hippocampal head morphology and to early adolescence as a crucial period for hippocampal integration into action- and reward-oriented cognition. The latter may constitute a developmental feature that conveys increased propensity for addictive disorders.

Keywords: Adolescence; Childhood; Hippocampus; Structural covariance.

Figure 1.

Stability and consistency of differentiation patterns measured with the aRI or the silhouette scores (A, B). Basic divisions of 2 and 3 subregions were more stable and consistent within hippocampal voxels and across age groups. A division into 3 subregions appeared optimal to study age related differences since it was a robust and consistent subdivision, which in addition captured age related differences across groups (C, D, E). Adults’ hippocampal differentiation patterns in (D) were previously obtained in a former study (Plachti et al., 2020).

Figure 2.

Structural covariance networks of left hippocampal subregions and their behavioral characterization. Hippocampal subregions’ associated unthresholded structural covariance networks (T>=1) are displayed for each of the investigated age group in the upper panel of the figure, whereas behavioral characterization of the structural covariance networks, performed with Neurosynth (r>=0.1), are summarized in the lower panel of the figure. In late childhood, anterior hippocampal subregions covaried with almost the whole brain, whereas posterior subregions’ structural covariance networks spatially expanded in middle adolescence. This pattern of results was also visible in networks’ behavioral associations. In late childhood, anterior hippocampus seems to covary with brain regions, involved in higher cognitive function including language, theory of mind, but also emotion and perception. In early adolescence, medial body-tail (blue) hippocampal subregion was linked to motivational and motor systems.

Figure 3.

Gene mapping of structural covariance networks associated with the left hippocampal differentiation pattern. Gene profiling of the unthresholded structural covariance networks was performed with Neurosynth and NeuroVault based on the Allen Human Brain Atlas. A maximum of 10 genes, which were positively correlated with the networks, FDR P < 0.05 corrected and explained more than 5% of the variance, were reported. In early adolescence structural covariance network of the medial body-tail (blue) hippocampal subregion was also genetically linked to motivation and reward systems. In late childhood, hippocampal tail (green) subregion is probably related to axonal and synaptic formation.