Differential Functional Connectivity in Anterior and Posterior Hippocampus Supporting the Development of Memory Formation

Abstract

Neuroimaging evidence suggests that the development of the hippocampus, a brain structure critical for memory function, contributes to the improvements of episodic memory between middle childhood to adulthood. However, investigations on age differences in hippocampal activation and functional connectivity and their contributions to the development of memory have yielded mixed results. Given the known structural and functional heterogeneity along the long axis of the hippocampus, we investigated age differences in the activation and functional connectivity in hippocampal subregions with a cross-sectional sample of 96 participants ages 8-25 years. We found that anterior and posterior hippocampus supported memory formation, and there was overall stability in memory-related hippocampal activation with age. Without taking account of memory outcome, direct contrast between subregions showed higher functional connectivity of anterior, compared to the posterior hippocampus, with regions in the inferior frontal and lateral temporal lobes, and higher functional connectivity of posterior, compared to the anterior hippocampus, with regions in the medial and superior frontal, inferior parietal, and occipital lobes. A direct contrast between the memory-related connectivity patterns of anterior and posterior hippocampus identified a region in the medial frontal cortex, with which anterior and posterior hippocampus was differentially functionally connected. Finally, we identified age differences in memory-related differential hippocampal functional connectivity with several frontal and visual/sensory cortices, underscoring the importance of examining age differences in the patterns of hippocampal connectivity. Moreover, the specific patterns of differential anterior and posterior functional connectivity indicate an increase in the functional specialization along the long axis of the hippocampus and a dynamic shift in hippocampal connectivity patterns that supports memory development.

Keywords: MRI; anterior; connectivity; development; hippocampus; memory; posterior.

Figure 1

An illustration of the subsequent memory paradigm. Participants studied indoor and outdoor scenes in the scanner and completed a recognition test later outside the scanner. Based on the responses during memory retrieval, encoding trials were labeled as Hit or Miss.

Figure 2

A schematic for the processing pipelines in this study. Manually traced hippocampal head, body, and tail were realigned to functional images [by applying deformation matrices derived from realigning proton density-weighted turbo spin-echo (PD-TSE) images to functional images] in order to construct individual anterior and posterior hippocampal Regions of Interest (ROIs). Functional images were preprocessed in two parallel streams, in native space or in MNI space, to facilitate different analytical needs. Analyses focusing on the hippocampus were conducted with unsmoothed images, whereas whole-brain analyses were conducted with smoothed images.

Figure 3

Manually segmented bilateral hippocampal head, body, and tail (in color) overlaid on top of structural images of one participant (light gray: PD-TSE high-resolution hippocampal image, dark gray: T1 MPRAGE whole-brain structural image).

Figure 4

Recognition accuracy by age. Across all participants, recognition accuracy (Hit rate—False Alarm rate) showed significant increase with age (r₍₉₄₎ = 0.46, p < 0.001).

Figure 5

Subsequent memory effects across the whole brain. Canonical subsequent memory effects were found in a range of brain regions, including bilateral hippocampi. p < 0.001, FDR-corrected at p < 0.01.

Figure 6

Hippocampal activations and subsequent memory effects. Top: Hippocampal activations showed a main effect of memory outcome (F_(1,91) = 19.58, p < 0.001), and an interaction between memory outcome and subregion [F_(1,91) = 19.86, p < 0.001; left hippocampus shown in (A); right hippocampus shown (B), *p < 0.05]. Bottom: Hippocampal activations did not show age effects. There were also no interactions between age and memory outcome, between age and subregion, or between age and hemisphere (all ps > 0.12; left hippocampus shown in C; right hippocampus shown D).

Figure 7

Differential functional connectivity between anterior and posterior hippocampus. (A) Difference in functional connectivity between anterior and posterior hippocampal subregions, regardless of memory outcome (red: higher functional connectivity with anterior compared to posterior hippocampus; blue: higher functional connectivity with posterior compared to anterior hippocampus). (B) Subsequent memory-related differences in functional connectivity between anterior and posterior hippocampus (blue: difference in functional connectivity with posterior compared to anterior hippocampus related to memory outcome).

Figure 8

Differential hippocampal functional connectivity with medial prefrontal cortex (mPFC) related to memory outcome. Reduced functional connectivity between anterior hippocampus and mPFC was found specifically for subsequently remembered trials.

Figure 9

Age modulated differential memory-related functional connectivity between anterior and posterior hippocampus in the inferior frontal gyrus (A), superior frontal gyrus (SFG) (B), postcentral gyrus (C), and occipital lobe (D). With an increase of age, posterior hippocampus showed a dynamic shift in its functional connectivity pattern with the prefrontal subregions, whereas anterior hippocampus showed decreased functional connectivity to sensory and visual regions.