Ovarian Hormones and Spatial Cognition

Spatial navigation (the ability to learn the layout of new places, plan, and execute routes from one place to another) is crucial for daily life. Around puberty, men begin to outperform women in navigation tasks that require the ability to create an accurate "cognitive map," or an internal representation of an environment's configuration (whereas women perform better in tasks such as retracing routes). Since this difference does not occur until puberty, it is possible that sex hormones may contribute to the emergence of these differences (via either ovarian hormones or androgens such as testosterone). The Spatial Thinking Lab is specifically interested in addressing how ovarian hormones shape spatial cognition performance in women, from both the short-term fluctuations that occur during the menstrual cycle, to the long-term sweeping changes in hormones that occur across the menopausal transition.

Determining the role of ovarian hormones and spatial cognition performance is important because spatial navigation ability is one of the earliest cognitive abilities to be affected in early stages of Alzheimer's Disease (AD), and women account for 2/3rds of all late-onset AD cases. These abilities decline even before episodic memory deficits can be reliably tested, which is the current gold standard for diagnosing AD (meaning that AD is only reliably diagnosed in later, harder-to-treat stages). Women are also at a significantly higher risk of developing AD with earlier onset of menopause (the total absence of menstrual cycles, significant reduction of estradiol, and increased levels of follicle-stimulating hormone). Estradiol has also been found to be associated with navigation performance in rodents, but little work has been conducted directly on humans (with the exception of mental rotation abilities, which may not directly measure navigation ability). 

Graduate student Lexie Topete has been interested in this line of work for her dissertation research, where she is currently looking at how ovarian hormones are associated with spatial cognition abilities in young women. She is currently taking the lead in two studies. The first study measures spatial cognition abilities at two different points in a woman's menstrual cycle (during high and low estradiol phases). In the second study, Lexie is collaborating with Dr. Emily Jacobs to examine the longer-term impacts of ovarian hormone suppression on navigation ability in young women who are being treated for endometriosis (i.e., are being chemically-induced with menopause to manage symptoms of endometriosis). Both these studies are being conducted to measure short- and long-term impacts of estradiol with spatial cognition abilities, while controlling for confounds of aging effects by only studying women between the ages of 18-40.

In collaboration with Dr. Emily Jacobs at UCSB and Dr. Elizabeth Chrastil at UC Irvine, Dr. Hegarty has also recently received an NIH grant from the National Institute of Aging to measure navigation abilities across the lifespan. This grant will measure a variety of spatial cognition abilities, including spatial learning, route knowledge, navigation strategy, and path integration in adults between the ages of 18-80. Aside from a wide battery of spatial tasks, participants will also have sex hormone concentrations measured, and midlife participants (ages 45-55) will undergo brain scans. We are particularly interested in studying navigation across the midlife transition, asking whether early age-related deficits in navigation vary by sex, especially given known changes in navigation-related brain regions during the menopausal transition (Jacobs & Goldstein, 2018), as well as changes in navigational strategy that arise during midlife (Yu et al., 2021). Advances in understanding these age-related changes could be critical for the early detection of individuals at risk for neurodegenerative diseases, before more overt cognitive symptoms arise.

References:

Jacobs, E. G., & Goldstein, J. M. (2018). The middle-aged brain: Biological sex and sex hormones shape memory circuitry. Current Opinion in Behavioral Sciences, 23, 84–91. https://doi.org/10.1016/j.cobeha.2018.03.009

Yu, S., Boone, A. P., He, C., Davis, R. C., Hegarty, M., Chrastil, E. R., & Jacobs, E. G. (2021). Age-related changes in spatial navigation are evident by midlife and differ by sex. Psychological Science, 32(5), 692-704. https://doi.org/10.1177/0956797620979185