Sex Differences in Cognitive Flexibility and Resting Brain Networks in Middle-Aged Marmosets.

Sex differences in human cognitive performance are well characterized. However, the neural correlates of these differences remain elusive. This issue may be clarified using nonhuman primates, for which sociocultural influences are minimized. We used the marmoset (Callithrix jacchus) to investigate sex differences in two aspects of executive function: reversal learning and intradimensional/extradimensional (ID/ED) set shifting. Stress reactivity and motor function were also assessed. In agreement with human literature, females needed more trials than males to acquire the reversals. No sex differences in ED set shifting or motivational measures were observed. The findings suggest enhanced habit formation in females, perhaps due to striatal estrogenic effects. Both sexes showed increased urinary cortisol during social separation stressor, but females showed an earlier increase in cortisol and a greater increase in agitated locomotion, possibly indicating enhanced stress reactivity. Independent of sex, basal cortisol predicted cognitive performance. No sex differences were found in motor performance. Associations between brain networks and reversal learning performance were investigated using resting state fMRI. Resting state functional connectivity (rsFC) analyses revealed sex differences in cognitive networks, with differences in overall neural network metrics and specific regions, including the prefrontal cortex, caudate, putamen, and nucleus accumbens. Correlations between cognitive flexibility and neural connectivity indicate that sex differences in cognitive flexibility are related to sex-dependent patterns of resting brain networks. Overall, our findings reveal sex differences in reversal learning, brain networks, and their relationship in the marmoset, positioning this species as an excellent model to investigate the biological basis of cognitive sex differences.

Oestradiol modulation of cognition in adult female marmosets (Callithrix jacchus).

The common marmoset (Callithrix jacchus) provides many advantages over traditional rodent and macaque species as a model for human ageing and may be very useful for studying the effects of sex steroids on cognitive and brain ageing. We present the first study examining the effects of oestrogens on cognitive function in female marmosets. Adult monkeys (3-5 years of age) were trained to a specific learning criterion on a battery of cognitive tasks preoperatively (object discrimination, delayed response with increasing delays and detour reaching with opaque box) and were tested on different versions of these tasks (object reversals, delayed response with randomised delays and detour reaching with clear box) after ovariectomy and simultaneous implantation with 17ß-oestradiol (E2 ) (n = 6) or blank (n = 6) Silastic capsules. Acquisition of a delayed matching-to-position task with a 1-s delay was also administered after completion of these tests. E2 -treated monkeys were significantly impaired on the second reversal and showed an increase in perseverative responding from reversals 1-3. Their performance also tended to be worse than that of control monkeys on the delayed response task. Performance acquisition on the delayed matching-to-position tended to be better in E2 -treated relative to control monkeys, although the group difference did not reach statistical significance. No effect of treatment was detected for detour reaching or affiliative behaviours. Overall, the findings indicate that E2 compromises performance on prefrontally-mediated tasks. The suggestion that E2 may improve acquisition on tasks dependent on the hippocampus will require further validation. These results are discussed in the context of dopaminergic and serotonergic signalling. We conclude that the marmoset is a useful new primate model for examining the effects of oestrogens on cognitive function.