Adult lifespan effects on functional specialization along the hippocampal long axis

There has been increasing attention to differences in function along the hippocampal long axis, with the posterior hippocampus proposed to have more variable signals that are well-suited to representing idiosyncratic details in memory, and the anterior hippocampus having less dynamic signals that are well-suited to integration. Whether long axis functional specialization persists into older age is not well-understood, despite known age-related declines in the level of detail in memories.

We used a large database of resting state fMRI data (n = 337 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 correlation of signals within hippocampal subregions. Our second approach was to measure functional connectivity between hippocampal subregions and the rest of the brain. For both approaches, we tested how well functional differences along the hippocampal long axis accounted for individual and age differences in episodic memory.

Within the hippocampus, we found a more positive age slope (i.e., increasing similarity of signals) for the most posterior hippocampal region compared to the intermediate and anterior region, consistent with the posterior hippocampus losing some of its heterogeneous signaling in older age. Patterns of whole-brain connectivity showed significant differences in the age trajectories between hippocampal subregions for a number of target regions, including several frontal connections. Yet we did not find strong evidence that either within-hippocampal signals or differences in functional connectivity were associated with age-related episodic memory decline.

Age differences in hippocampal long axis functional organization were apparent during rest but were limited in how well they accounted for memory decline.