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

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 [18F]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. SIGNIFICANCE STATEMENT: We report how whole-brain networks are involved in spatial navigation behaviors and how normal aging alters these network patterns in nonhuman primates. This is the first study to examine whole-brain network activity in young or old nonhuman primates while they actively or passively traversed an environment. The strength of this study resides in our ability to identify and differentiate whole-brain networks associated with specific navigational behaviors within the same nonhuman primate and to compare how these networks change with age. The use of high-resolution PET (microPET) to capture brain activity of real-world behaviors adds significantly to our understanding of how active circuits critical for navigation are affected by aging.