Age-related functional connectivity along the hippocampal longitudinal axis

Accumulated evidence points toward a long-axis functional division of the hippocampus, with its anterior part primarily associated with emotional processes and the posterior with navigation and cognition. It is yet unclear, however, how functional connectivity between areas along the hippocampal longitudinal axis and other brain regions differ, and how they are affected by age. Applying an anatomically driven general linear model-based functional connectivity analysis on a large database of resting-state fMRI data, we demonstrate that independent of age, the posterior hippocampus is functionally connected primarily with sensory and motor areas, the middle hippocampus with the default mode network, and the anterior with limbic and prefrontal regions. Along with an age-related disintegration of intra-hippocampal BOLD signal uniformity, the middle and posterior sub-regions exhibit mostly decreases in their functional connectivity with cortical regions, whereas the anterior hippocampus and ventral striatum appear to become more synchronized with age. These findings indicate that long-axis hippocampal areas are tuned to particular functional networks, which do not age in a unified manner.