Neurobiological correlates of behavioral and cognitive performance in nonhuman primates

Animals in experiments are traditionally grouped by experimental treatment. Although this is a valuable way to differentiate the groups, alternatively, groups can be distinguished based on cognitive performance. Performance based analysis can yield valuable insights, corresponding to behavior and/or cognition, that might not otherwise be observed. As an example of such an analysis, we discuss a cohort of elderly female rhesus macaques who participated in a spatial food port maze navigational test. Circadian activity and pharmacological MRI (phMRI) were assessed in these monkeys in vivo and radioligand binding was assessed in post-mortem tissue. Based on cognitive performance in the spatial maze, the cohort of monkeys was divided into Good Spatial Performers (GSP) and Poor Spatial Performers (PSP). GSP animals were more active during the day and less active at night compared to PSP animals. In addition, GSP animals had a higher percentage change in blood-oxygen-level-dependent (BOLD) signal after a scopolamine challenge, a non-specific muscarinic receptor antagonist, compared to PSP animals. Post-mortem radioligand experiments demonstrated that hippocampal muscarinic type 1 (M1) maximum receptor binding and receptor binding affinity, hypothesized to have an integral role in spatial learning and memory, was significantly greater in the hippocampus of GSP than PSP animals. In contrast to the hippocampus, M1 receptor binding was not significantly different in the prefrontal cortex (PFC). Muscarinic type 2 (M2) maximum receptor binding and receptor binding affinity were not significantly different between the two groups in either brain region. Finally, there were positive correlations between circadian measures and the percentage change in BOLD signal following the scopolamine challenge, as well as M1 receptor binding measures. Thus, GSP animals sleep more and have anenhanced M1 receptor function. These data demonstrate the close relationship between BOLD signal changes, circadian activity, and M1 receptor binding parameters. Distinguishing groups based on cognitive or behavioral performance is valuable for studying neurobiological correlates of performance in nonhuman primates.