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

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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.*****