Sex differences in cognition, emotional reactivity, and motor ability in gonadally-intact middle-aged marmosets (Callithrix jacchus)

Sex differences in cognition are well documented. Women outperform men on measures of perceptual speed and verbal abilities, while men outperform women on tests of spatial processing. Robust sex differences also exist in stress responses. However, it is unclear how these sex differences change over time and whether males and females follow different trajectories of age-related cognitive decline. Studies in nonhuman primate models can help resolve this issue. The common marmoset (Callithrix jacchus) is a New World primate with a short lifespan that can perform complex cognitive tasks in computerized settings that are comparable to those used with humans. The present study is part of a longitudinal project aimed at determining whether males and females follow different trajectories of cognitive aging. This report focuses on sex differences at study entry. Thirteen marmosets (7 females), aged 4-6 years were tested on a comprehensive battery of tasks assessing cognitive function, motor skills and emotional reactivity. For cognition, monkeys were initially trained on a simple visual discrimination problem, followed by reversal learning using the Cambridge Neuropsychological Test Automated Battery (CANTAB). They also performed the Hill-and-Valley task as a measure of fine motor skills. To assess emotional reactivity, each marmoset was separated from their colony for 7 hours. Behavioral assessments, which involved recording the occurrence of approximately 25 behaviors, occurred a total of 6 times: immediately before separation, 3 times during separation, immediately after separation, and 24-hr later. No sex difference was found for simple discrimination, but males tended to perform better than females on the reversal learning task. No sex difference was observed in motor skills. During separation from the colony, females were more reactive than males, as indicated by more agitated locomotion, and vocalizations. Together, these findings expand upon previous studies and demonstrate sex differences in reversal learning and emotional reactivity in gonadally-intact middle-aged marmosets. As the study progresses, we should be able to determine the neural correlates of these sex differences and how they may change with aging. Supported by NIH grant AG04626

Robustness of sex-differences in functional connectivity over time in middle-aged marmosets

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\u27s disease

Testosterone Treatment Does Not Facilitate Prefrontal Cortex Mediated Cognition in Male Marmosets (callithrix jacchus)

Aging in men is associated with decreases in serum testosterone (T) and a decline in cognitive abilities. We sought to clarify the relationship between T, aging and cognition using the common marmoset (callithrix jacchus), which has been shown to be a useful model of human aging. Ten castrated male marmosets (ages 3-8) were given weekly injections of either T cypionate dissolved in cottonseed oil (T, n = 5) or cottonseed oil alone (controls, n = 5). Cognitive function was assessed with two tasks, the object reversals (OR) and the delayed response (DR). Marmoset behavior was recorded twice daily using a modified frequency scoring system, measuring 20 target behaviors in 15-s intervals over 5-min. For the OR task, no effect of group (F (1,8) = .51, p = .50), reversal (F (3,24) = .527, p = .67), or group x reversal interactions (F (3,24) = .640, p = .60) was found in the number of correct trials. There was a significant effect of outcome on response latency, with all monkeys having longer latencies on incorrect trials (F (1,2451) = 45.36,

Sex differences in inhibitory control in socially-housed baboons (Papio papio)

International audienceInhibitory control is an important component of executive function. An emerging literature in humans suggests that inhibitory control is sexually dimorphic and modulated by sex steroids, but evidence for such a link in nonhuman animals is scarce. In this study, we examined the effects of menstrual cycle and biological sex on response inhibition, as measured by a Stop-Signal task, in the baboon (Papio papio). The monkeys (n = 13) were socially-housed, with voluntary access to multiple touchscreen computerized stations. The task required monkeys to inhibit prepotent responses (touching a target, ``Go'' trials) following the appearance of a visual stop signal on 25% of the trials (''Stop'' trials). The cognitive data, consisting of computerized records of the monkeys' performance on the Stop-Signal task over a year of testing, were matched to records of female sexual swellings: Same-day menstrual and cognitive data were available for 5 females, aged 5-18 years. These data were compared to those of 8 males (5-14 years old) performing the Stop-Signal task over the same time period. Contrary to our hypothesis, performance on the task was not significantly affected by the phase (ovulatory vs. luteal) of the cycle in females. However, males were slower than females on Go trials and were less efficient in inhibiting responses on Stop trials. Slower responses in males were indicative of a speed-accuracy trade-off, as overall accuracy was also better in males than in females. Analyses of trial history indicated that males did not speed as much as females following a successful Go trial, but did not differ from females in post-error slowing or post inhibiting responses. Overall, the data show that biological sex modulates Stop-Signal performance in the baboon, with males exhibiting slower response execution overall, less efficient inhibition, but greater accuracy than females. This pattern of sex differences may reflect motivational sex differences in which males emphasize accuracy rather than speed. Interestingly, these sex differences do not seem to vary as a function of ovarian hormones in females. Males' greater focus on accuracy is possibly due to enhanced sensitivity to reward mediated by testosterone levels. (C) 2016 Elsevier B.V. All rights reserved