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

项目总结/摘要 动物研究表明，海马体的结构和功能都随着大脑皮层的波动而变化。 性类固醇在女性月经周期;然而，最近的调查产生了混合的结果， 人类海马体是否也发生了可测量的变化。大多数人类研究试图找出 与死亡相关的大脑变化使用体积来评估变化;然而，体积是一种粗略的测量方法， 无法解释可能发生的微观结构变化。磁共振弹性成像（MRE）是 一种用于获取生物组织的机械特性的非侵入性测量的新兴工具（即， 粘弹性），从而提供微观结构组织健康的量度。本研究旨在：（1）研究 作为神经基质的组织粘弹性对海马微结构的波动敏感， 以及（2）确定依赖于月经周期的记忆结果的变化， 伴随卵巢激素（即，雌二醇）波动和海马微结构的相关变化。 为了实现这些目标，MRI/MRE，血液和认知数据将从自然骑自行车的女性中收集， 18到40岁之间的典型荷尔蒙特征血液将用于确认低雌二醇的时期 (i.e.,在月经开始时）和高雌二醇（即，在排卵前）。 MRI/MRE扫描以及旨在评估语言和空间认知障碍依赖性的认知电池 然后将从每个女性那里收集两次记忆：当雌二醇高与低时。根据来自 动物文献，数据分析将集中在海马及其子领域。预计在 当雌二醇低时，海马粘弹性，特别是在CA 1/2亚区，将相对较高， 当雌二醇高时，粘弹性将相对较低，表明微结构组织的变化。 此外，可以预期，当雌二醇高与低时，海马依赖性记忆将发生变化， 海马粘弹性和海马依赖性记忆表现之间关系也将 在月经周期的这两个阶段是不同的。这项工作将使地雷危险教育成为研究的有用工具 认知神经科学，旨在确定微妙的微观结构变化，并强调重要性， 在评估结构变化时选择适当的神经成像工具。因为一些批评公众 健康问题（即，心血管疾病、抑郁症、多发性硬化症、阿尔茨海默病） 不成比例地影响妇女和激素波动（特别是雌激素）有助于发展， 许多这些疾病的发作和/或进展，非侵入性评估这些疾病之间关系的能力 激素波动以及神经解剖学和功能变化对于实施有效且 有针对性的治疗计划。建议将地雷风险教育作为满足这一需要的工具。此外，这次演示将有 对未来科学的广泛影响，旨在量化区域微观结构相关的细微变化， 例如，精神健康结果和神经退行性疾病。

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.