Hippocampal and caudate network specificity is altered in older adults

Abstract The hippocampal and the caudate networks, defined by their intrinsic resting state functional connectivity (FC), exhibit strong network specificity. This is reflected as strong within-network and weak between-network FC, as well as their dissociable roles in cognition. Aging typically reduces the specificity of brain networks. However, whether the hippocampal and caudate networks show age-related decreases in network specificity is unclear. Further, whether any age-related decreases in network specificity are due to reduced within-network FC, increased between-network FC, or some combination of both, is also unclear. Using a large-scale fMRI data set acquired from healthy younger ( n = 101, aged 18–40 years) and older ( n = 101, 55–75 years) adults, networks centered on the left anterior hippocampus and the head of the right caudate nucleus were compared. These sub-regions were chosen based on their distinct contributions to cognition, their known interactions, and their susceptibility to age-related changes. A mixed effect model was used to identify brain regions where network specificity differed between groups. For younger adults, hippocampal network specificity was strong in the medial frontal gyrus (MFG), while caudate network specificity was strong in the basal nuclei. However, network specificity in these same regions was significantly reduced in older adults. Reduced specificity in each network was due to a weakening of within-network connectivity rather than an increase in between-network connectivity. These results indicate that hippocampal and caudate network specificity decreases with advancing age, raising the possibility that these reductions may contribute to age-related changes in memory. Impact Statement Older adults represent an increasing proportion of the population, thus increasing the urgency for us to understand the neurological changes that contribute to age-related memory loss. Aging is associated with a loss of network specificity, reflected as reduced within-network, and increased between-network, connectivity. My work shows that this phenomenon is not restricted to the hippocampal and caudate networks, which are critical for learning facts and skills, respectively: Both networks decreased in network functional connectivity. These results raise the possibility that “blurring” between these networks relates to age-related memory loss, possibly as a compensatory mechanism to protect memory in old age.