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

自然循环女性荷尔蒙波动引起的海马微观结构和海马依赖性记忆的变化

• 批准号: 10527084
• 负责人: Hillary Schwarb
• 金额: $ 23.79万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527084
• 关键词: Accounting; Address; Affect; Age; Alzheimer' s Disease; Animal Experimentation; Animals; Assessment tool; Behavioral; Biological; Blood; Brain; Brain region; Cardiovascular Diseases; Cognition; Cognitive; Data; Data Analyses; Dendritic Spines; Development; Diagnosis; Disease; Estradiol; Estrogens; Evaluation; Female; Future; Gonadal Steroid Hormones; Health; Hippocampus (Brain); Hormonal; Hormones; Human; Individual; Intervention; Investigation; Literature; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Measurable; Measures; Memory; Menstrual cycle; Menstruation; Mental Depression; Mental Health; Mental disorders; Methods; Multiple Sclerosis; N-Methyl-D-Aspartate Receptors; Neurodegenerative Disorders; Neurologic; Outcome; Ovarian; Ovarian hormone; Ovulation; Participant; Performance; Phase; Population; Positioning Attribute; Property; Public Health; Research; Resolution; Rodent; Scanning; Science; Steroids; Structure; Synapses; Techniques; Time; Tissues; Treatment outcome; Validation; Woman; Work; base; behavior influence; behavioral outcome; brain behavior; clinically relevant; cognitive neuroscience; cost; density; design; effective therapy; in vivo; mechanical properties; men; neuroimaging; non-invasive imaging; relating to nervous system; standard measure; success; targeted treatment; tool; treatment planning; viscoelasticity; young adult

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.

项目概要/摘要 动物研究表明，海马体的结构和功能都随着脑力波动而变化。 然而，最近的研究得出了不同的结果： 大多数人类研究都试图确定人类海马体是否也发生了可测量的变化。 与激素相关的大脑变化使用体积来评估变化；然而，体积是一个粗略的衡量标准 无法解释可能发生的微观结构变化。 一种新兴工具，用于获取生物组织机械性能的非侵入性测量（即， 粘弹性）提供了微观结构组织健康的衡量标准。拟议的工作旨在（1）调查。 组织粘弹性作为对海马微观结构发生的波动敏感的神经基质 整个月经周期以及（2）确定海马依赖性记忆结果的变化，这些变化 伴随卵巢激素（即雌二醇）波动和海马微观结构的相关变化。 为了实现这些目标，将从自然骑自行车的女性身上收集 MRI/MRE、血液和认知数据。 18 至 40 岁之间的典型荷尔蒙状况。血液将用于确认低雌二醇时期 每个参与者的雌二醇水平（即月经开始时）和高雌二醇（即排卵前）。 MRI/MRE 扫描以及旨在评估言语和空间海马依赖性的认知电池 然后，将从每个女性身上收集两次记忆：雌二醇何时高或何时低。 动物文献中，数据分析预计将集中于海马体及其子领域。 当雌二醇较低时，海马粘弹性，特别是CA1/2子区，会相对较高，并且 当雌二醇较高时，粘弹性将相对较低，表明微观结构组织发生变化。 此外，预计当雌二醇高与低时，海马依赖性记忆会发生变化，并且 海马粘弹性与海马依赖性记忆表现之间的关系也将 这项工作将使 MRE 成为研究的有用工具。 认知神经科学旨在识别微妙的微观结构变化并强调 在评估结构变化时选择适当的神经影像工具，因为有几个关键的公众。 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） 对女性的影响尤为严重，荷尔蒙波动（特别是雌激素）有助于发育， 许多这些疾病的发作和/或进展，非侵入性评估之间关系的能力 激素波动以及神经解剖学和功能变化对于实施有效性和功能至关重要 提出有针对性的治疗计划作为满足这一需求的工具。 对未来科学的广泛影响，旨在量化相关区域微观结构的微妙变化， 例如，心理健康结果和神经退行性疾病。