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

项目摘要/摘要 动物研究表明，海马体的结构和功能都会随着 性激素贯穿女性月经周期；然而，最近的研究得出了不同的结果，如 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确定 荷尔蒙相关的大脑变化使用体积来评估变化；然而，体积是一种粗略的衡量标准， 无法解释可能正在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)提供微结构组织健康的度量。拟议的工作旨在(1)调查 组织粘弹性作为神经基质对海马区微结构的波动敏感 跨月经周期和(2)确定海马体依赖记忆结果的变化 伴随着卵巢激素(即雌二醇)的波动和海马区微结构的相关变化。 为了达到这些目标，将从自然骑自行车的妇女那里收集MRI/MRE、血液和认知数据。 年龄在18到40岁之间的典型荷尔蒙特征。血液将被用来确认雌激素水平过低的时期 (即月经开始时)和高雌二醇量(即排卵前)。 MRI/MRE扫描以及用于评估语言和空间海马区依赖的认知电池 然后，将从每个女性身上收集两次记忆：雌二醇水平高的时候和低水平的时候。基于以下研究结果 在动物文献中，数据分析将重点放在海马体及其子领域。预计 当雌二醇水平较低时，海马区的粘弹性相对较高，尤其是在CA1/2亚区。 当雌二醇含量较高时，粘弹性相对较低，表明微结构组织发生了变化。 此外，可以预见，当雌二醇水平较高或较低时，海马区依赖记忆将发生变化。 海马体粘弹性和海马体依赖记忆能力之间的关系也将 在月经周期的这两个阶段是不同的。这项工作将使MRE成为研究的有用工具 认知神经科学的一部分，试图识别微妙的微结构变化，并强调 在评估结构变化时选择适当的神经成像工具。因为几个批评公众 健康问题(如心血管疾病、抑郁症、多发性硬化症、阿尔茨海默病) 对女性的影响不成比例，荷尔蒙波动(特别是雌激素)有助于发育， 许多这些疾病的发病和/或进展，无创评估之间的关系的能力 荷尔蒙的波动以及神经解剖和功能的改变是实施有效和 有针对性的治疗计划。MRE就是为了满足这种需求而提出的一种工具。此外，这一演示将具有 对未来科学的广泛影响，寻求量化相关区域微观结构的细微变化， 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.