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Neural and physiological correlates of sex differences in cognition in the marmoset (Callithrix jacchus)

Abstract
Sex differences in cognitive performance are well characterized within the literature; however, the neural and physiological correlates of these differences remain elusive. We propose the common marmoset as an ideal model for understanding the neural and physiological underpinnings of sex differences in cognition. The first goal of this dissertation was to examine sex differences in motor ability, stress reactivity, and cognitive ability. The second goal was to examine the ways in which brain metabolite concentration, as measured through Magnetic Resonance Spectroscopy (MRS), and Resting State Functional Connectivity (rsFC) predicted cognitive performance. Motor ability was characterized using the Hill and Valley task, a fine motor task. Both male and female animals showed superior right hand performance when ipsilateral hand and eye coordination was required. When the contralateral hand and eye coordination was required, females outperformed males, potentially indicating superior sensory-motor integration in females. Stress reactivity was measured using a 7-hour social separation paradigm. While overall increases in urinary cortisol did not differ based on sex, females showed a significantly greater rise in cortisol in the first half of the separation. Additionally, females showed a greater increase in agitated locomotion during separation, indicating greater stress responsivity. Cognition was assessed through Simple Reversal Learning and Intradimensional/Extradimensional (ID/ED) set shifting tasks. Females required more trials to reach learning criterion on the reversal learning trials, indicating poorer performance on this task. No sex differences in ED set shifting were observed. Metabolite concentrations within the prefrontal cortex (PFC) were assessed using 1H MRS. Glx concentration (glutamate + glutamine) in the PFC was correlated with reversal learning performance, and this correlation was significant in males, but not in females. Correlations between resting state networks and reversal learning were investigated using resting state fMRI. Greater network extension of the PFC network was associated with better reversal learning in males, but not in females. Altogether, these findings reinforce the usefulness of the marmoset model of human cognitive performance and indicate that cognition, brain function, and their relationship differ between the sexes.
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