Psychophysiological investigation of 17ß-estradiol effects on memory functions under stress in humans

我们如何参与、学习、编码和检索世界上的元素，在个人内部和个人之间都是不同的。来自动物和人类的证据支持17-雌二醇(E2)对多种记忆过程的调节作用。具体地说，E2对工作记忆和情景记忆以及不同记忆系统的招募的影响已经被记录在案。然而，现有的证据并不支持E2在女性记忆过程中的作用，研究未能观察到循环中的E2对记忆的影响。 在人类中，有证据被忽视，包括我自己的研究中的一些证据，这些证据支持压力和卵巢激素在预测行为方面的交互作用。此外，压力暴露已被证明与E2调节相同的记忆域；大量动物证据证实了E2和压力对记忆过程的交互影响。急性压力的程度(轻度与中度)以及压力的慢性化都被发现对记忆过程的影响是适度的。最后，来自动物和人类的证据表明，E2和压力对记忆过程的交互影响可能是通过增加生理应激系统的活动来调节的，特别是交感神经系统。 我的长期目标是开发一种人类雌激素效应的生物行为模型，该模型可以解释环境和个体差异(也称为逐个人的环境模型)。这个项目的最终结果是解释雌二醇水平的变化何时、如何以及在谁身上影响行为。首先，为了研究环境因素如何塑造E2对女性记忆功能的影响，我的短期目标是从经验上验证和阐明E2在压力下的行为和生理影响。为此，我们将研究急性应激和雌二醇水平的自然变化对特定记忆过程(工作记忆、情景记忆和记忆系统招募)的综合影响。同样，将评估不同水平的慢性应激如何调节E2对记忆过程的影响。最后，将评估生理应激系统可能的调节作用。这些实验将作为我的研究计划的基础，我计划从三个主要方向进行扩展：1)通过药物操作的机械性；2)使用脑电图学等技术的神经生理学；3)通过研究其他认知过程，如恐惧消退和认知灵活性，从行为上进行扩展。 这项研究计划调和了人类和动物文献内部和之间的系统性不一致，将为开发E2对行为的影响的按人情境模型奠定基础。最终，这项工作将对理解个体间和个体内部认知功能的差异及其在教育、个人或职业背景下的表现具有更广泛的意义。

How we attend, learn, encode and retrieve elements of the world varies within and between individuals. Evidence from animals and humans supports the regulatory role of 17-estradiol (E2) on multiple memory processes. Specifically, the effects of E2 have been documented for working memory and episodic memory, and for the recruitment of different memory systems. However, the existing evidence does not support the role of E2 on women's memory processes, with studies failing to observe an effect of circulating E2 on memory. Overlooked in humans is evidence, including some from my own research, that supports the interactive effect of stress and ovarian hormones in predicting behaviour. Furthermore, stress exposure has been shown to regulate the same memory domains as E2; substantial animal evidence confirms the interactive effects of E2 and stress on memory processes. The degree of acute stress (mild vs. moderate) as well as the chronicity of stress have all been found to moderate effects of E2 on memory processes. Finally, evidence from both animals and humans suggests that the interactive effects of E2 and stress on memory processes might be mediated by increased activity in physiological stress systems, particularly the sympathetic nervous system. My long term objective is to develop a bio-behavioural model of E2 effects in humans that accounts for environmental and individual variations (also called a context by person model). The end result of this program is to explain when, how and in whom changes in E2 levels impacts behaviour. First, to investigate how environmental factors shape the effect of E2 on women's memory functions, my short term objectives are to empirically validate and elucidate the behavioural and physiological effects of E2 under stress. To do so, the combined effects of acute stress and natural variation in E2 levels on specific memory processes (working memory, episodic memory and memory system recruitment) will be investigated. Similarly, how varying levels of chronic stress exposure regulate the effect of E2 on memory processes will be assessed. Finally, possible mediating effects of the physiological stress systems will be assessed. These experiments will serve as the foundation for my research program which I plan to expand in three main directions: 1) mechanistically through pharmacological manipulation 2) neurophysiologically with the use of technologies such as electroencephalography and 3) behaviorally by investigating other cognitive processes such as fear extinction and cognitive flexibility. Reconciling systematic inconsistencies within and between human and animal literature, this research program will lay the groundwork for the development of a context by person model of E2 effects on behavior. Ultimately, this work will have broader implications for understanding inter- and intra-individual differences in cognitive functions and their manifestation in educational, personal or occupational contexts.