Impact of Endocrine Age on Working Memory Circuitry
Sex steroid hormones are neuromodulators of learning and memory. During the menopausal transition, estradiol and progesterone production declines by ~90%, while gonadotropin (Follicle Stimulating Hormone) levels rise considerably. However, human cognitive neuroscience studies have largely overlooked the relationship between the brain and reproductive endocrine system despite the fact that estrogen and progesterone receptors are expressed throughout cortex. The UCSB Healthy Midlife Aging Study, a multimodal neuroimaging study, works to fill this unexplored area by characterizing the neural and cognitive changes that unfold in midlife, as a function of endocrine age. In this analysis, we examined the impact of menopausal status on working memory (WM) performance and task-evoked fMRI activity. Midlife adults from the Santa Barbara community underwent in-person neuropsychological evaluations, an MRI scan, and serological hormone assessments. Reproductive stage (pre-, peri-, post-menopause) was determined via STRAW-10 guidelines. Participants completed an n-back WM paradigm during fMRI scanning to assess sustained activity in WM circuity as a function of load (0, 2, 3-back blocks) and transient changes in response to specific trial types with an increasing demand for cognitive control (non-targets, targets, lures). Behaviorally, higher n-back loads and more difficult trial types correlated with lower task accuracy and longer response times. Across reproductive stages, there were no differences in task accuracy or response time. fMRI load-dependent changes in BOLD reveal that endocrine age does not significantly impact working memory circuitry. These findings begin to address the critical knowledge gap in women’s brain health.