Adult lifespan effects on functional specialization along the hippocampal long axis
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There has been increasing attention to differences in function along the hippocampal long axis, with posterior regions proposed to have properties that are well suited to representing fine-grained details and coarser representations in anterior regions. Whether long axis functional specialization persists into older age is not well understood, despite well documented memory changes in older age. In this study, we used a large database of fMRI data (n =323 humans of both sexes included) from across the adult lifespan (ages 18-88) to determine the degree of functional differentiation across the hippocampal posterior-anterior axis. Our first approach was to measure the similarity among signals within each hippocampal subregion. We found that intra-region signals within the most posterior hippocampal subregion became more similar in older age, but did not relate to episodic memory performance. As a second approach, we measured functional connectivity between hippocampal subregions and the rest of the brain. The functional connectivity profiles of the posterior and anterior hippocampal subregions became more distinct from one another with increasing age, and age-related reductions in connectivity were strongest for the intermediate portion of the hippocampus. In contrast, anterior hippocampal functional connectivity remained relatively stable across the adult lifespan, and stronger anterior hippocampus connectivity with the anterior cingulate was associated with better episodic memory in older adults, suggesting that the anterior hippocampus may help some older adults compensate for age-related changes to more posterior hippocampal regions to preserve episodic memory.
Significance Statement
There is an increasing understanding that differences across the hippocampal long axis help give rise to multifaceted episodic memories. Yet, whether hippocampal long axis differentiation persists into older age is not well understood. Here, we show that older age exaggerates the differentiation along the hippocampal long axis due largely to changes in posterior and intermediate portions of the hippocampus. Anterior hippocampal signals were more stable and were sometimes associated with better episodic memory performance in older age. These findings suggest that functional declines in posterior hippocampus may be a normal part of healthy aging, but that some older adults offset this decline by upregulating anterior hippocampal function, which in turn helps maintain episodic memory.
