Changes in hippocampal microstructure and hippocampal-dependent memory accompanying hormonal fluctuation in naturally cycling women

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Animal research has shown that both the structure and function of the hippocampus change with fluctuations in sex steroids across the female menstrual cycle; however, recent investigations have produced mixed results as to whether measurable changes also occur in the human hippocampus. Most human studies that seek to identify hormone-related brain changes have used volume to assess change; volume, however, is a gross measure that cannot account for microstructural changes that may be occurring. Magnetic resonance elastography (MRE) is an emerging tool for acquiring noninvasive measures of the mechanical properties of biological tissue (i.e., viscoelasticity) providing a measure of microstructural tissue health. The proposed work seeks to (1) investigate tissue viscoelasticity as a neural substrate sensitive to fluctuations in hippocampal microstructure that occur across the menstrual cycle and (2) to identify changes in hippocampal-dependent memory outcomes that accompany ovarian hormone (i.e., estradiol) fluctuations and associated changes in hippocampal microstructure. To address these aims, MRI/MRE, blood, and cognitive data will be collected from naturally cycling women with a typical hormonal profile between the ages of 18 and 40. Blood will be used to confirm periods of low estradiol (i.e., at the start of menstruation) and high estradiol (i.e., just before ovulation) for each individual participant. MRI/MRE scans as well as a cognitive battery designed to assess verbal and spatial hippocampal-dependent memory will then be collected twice from each woman: When estradiol is high vs. low. Based on findings from the animal literature, data analysis will focus on the hippocampus as well as its subfields. It is expected that hippocampal viscoelasticity, particularly in subfield CA1/2, will be relatively high when estradiol is low, and that viscoelasticity will be relatively low when estradiol is high indicating a change in microstructural organization. Further, it is anticipated that hippocampal-dependent memory will vary when estradiol is high vs. low and that the relationship between hippocampal viscoelasticity and hippocampal-dependent memory performance will also differ across these two phases of the menstrual cycle. This work will establish MRE as a useful tool for the study of cognitive neuroscience that seeks to identify subtle microstructural alterations and highlight the importance of choosing appropriate neuroimaging tools when assessing structural changes. Because several critical public health concerns (i.e., cardiovascular disease, depression, multiple sclerosis, Alzheimer’s disease) disproportionately affect women and hormonal fluctuations (particularly estrogen) contribute to the development, onset, and/or progression of many of these disorders, the ability to noninvasively assess the relationship between hormone fluctuation and both neuroanatomical and functional change is essential for implementing effective and targeted treatment plans. MRE is proposed as a tool to meet this need. Further, this demonstration will have broad implications for future science that seeks to quantify subtle alterations in regional microstructure relevant, for example, to mental health outcomes and neurodegenerative disease.