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.
