Abstract
Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer’s disease.
Highlights
Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species
Consistent with greater nodal interactions observed in males (Fig. 1), there was greater clustering coefficient (k15–40 p = 0.05) and a trend for greater graph strength (k30–40 p = 0.1), in males compared to females (Fig. 2)
There was a non-significant trend for node strength correlating with the reversal index (RI) in both females and males, with a greater RI reflecting poorer reversal performance (Fig. 3)
Summary
Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. We used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Monkeys have to select the rewarded stimulus in pairs of stimuli (discrimination) and reverse their response as the previsouly unrewarded stimulus becomes the rewarded stimulus (reversal) This test evaluates cognitive flexibility, which can be assessed by recording the number of trials monkeys need to perform a reversal relative to a discrimination. These cognitive differences are strongly correlated with sex differences in resting-state functional connectivity (rsFC) assessed using magnetic resonance imaging (MRI)[9]
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