Network Patterns Associated with Navigation Behaviors Are Altered in Aged Nonhuman Primates

Abstract

The ability to navigate through space involves complex interactions between multiple brain systems. Although it is clear that spatial navigation is impaired during aging, the networks responsible for these altered behaviors are not well understood. Here, we used a within-subject design and [18 F]FDG-microPET to capture whole-brain activation patterns in four distinct spatial behaviors from young and aged rhesus macaques: constrained space (CAGE), head-restrained passive locomotion (CHAIR), constrained locomotion in space (TREADMILL), and unconstrained locomotion (WALK). The results reveal consistent networks activated by these behavior conditions that were similar across age. For the young animals, however, the coactivity patterns were distinct between conditions, whereas older animals tended to engage the same networks in each condition. The combined observations of less differentiated networks between distinct behaviors and alterations in functional connections between targeted regions in aging suggest changes in network dynamics as one source of age-related deficits in spatial cognition.

Network Models Predict That Pyramidal Neuron Hyperexcitability and Synapse Loss in the dlPFC Lead to Age-Related Spatial Working Memory Impairment in Rhesus Monkeys

“…Such units could be well-suited for extending the DRSTsp model introduced here to simulate choice of the novel spatial cue and related internal signals, plus the full 3 × 6 array of wells presented to the monkeys during the DRSTsp. There is evidence that aging affects information flow between cortical regions, which can contribute to working memory impairment (Engle et al, 2016;Lee et al, 2016;Proskovec et al, 2016;King et al, 2018;Koen et al, 2019). Any such age effects must be examined in concert with the changes to dlPFC synapses and neuronal excitability, to predict the extent to which these concomitant changes compound vs. partially compensate each other.…”

Network models predict that pyramidal neuron hyperexcitability and synapse loss in the dlPFC lead to age-related spatial working memory impairment in rhesus monkeys

“…Such units could be well-suited for extending the DRSTsp model introduced here to simulate choice of the novel spatial cue and related internal signals, plus the full 3x6 array of wells presented to the monkeys during the DRSTsp. There is evidence that aging affects information flow between cortical regions, which can contribute to working memory impairment (Engle et al, 2016;Lee et al, 2016;Proskovec et al, 2016;King et al, 2018;Koen et al, 2019). Any such age effects must be examined in concert with the changes to dlPFC synapses and neuronal excitability, to predict the extent to which these concomitant changes compound versus partially compensate each other.…”

Hippocampal contributions to novel spatial learning are both age-related and age-invariant

“…A higher score on this index indicated more differentiated environmental-specific neural representations (remapping) and a lower score indicated de-differentiation or less distinct network patterns. Previous work has suggested that older adults and nonhuman primates show greater de-differentiation for overlapping stimuli than do younger adults (8)(9)(10)(11)(12)17). This may be particularly true for scenes, suggesting a parallel with navigation, although some studies have also supported the idea that these findings are age-invariant (18)(19)(20).…”

“…In the CA3 subfield of the rodent hippocampus, old rat hippocampal representations do not strongly distinguish between two different environments (i.e., dedifferentiation) (7), suggesting a possible alteration in a computational mechanism termed "pattern separation." This difficulty differentiating separate environments may relate more broadly to age-related network de-differentiation in human and nonhuman primate studies (8)(9)(10)(11)(12), although this, too, has not been studied across the lifespan.…”