Anxiety and Working Memory Function in Women: Exploring the Role of Dopamine and Ovarian Hormones

项目摘要 焦虑是全球第六大残疾原因，女性的患病率是男性的两倍。 重要的是，焦虑与前额叶皮层（PFC）功能降低有关，该功能对认知功能至关重要。 例如工作记忆。尽管临床前模型已经提出了复杂的交互作用， 焦虑和雌二醇通过调节前额叶多巴胺（DA）对工作记忆的影响，没有研究 Date研究了这些模型在人类女性中的转化意义。为了弥补这一差距， 一个项目的目的是研究多巴胺和雌二醇对焦虑之间关系的影响，焦虑是一个核心认知特征， 焦虑，和神经振荡活动（即，θ-γ耦合 在女性中。具体目的是：（1）建立焦虑与TGC之间的关系;（2）考察焦虑在TGC中的作用 基础DA在焦虑和TGC之间的关系;（3）检查雌二醇在焦虑和TGC之间的作用。 焦虑与TGC的关系基于理论和实证研究， 通过在认知系统上增加额外的“负荷”来降低性能，我希望担心与此相关。 降低TGC，特别是在对PFC功能施加高负载的更困难的任务条件下。到 鉴于基础DA在工作记忆功能中的关键作用，将研究其作用。 具体来说，DA与工作记忆功能呈倒U型关系， DA水平促进最佳工作记忆功能，而过多或过少的DA则会损害。因此，在本发明中， 我预计，在循环DA较低的个体中，较高的担忧将与较低的TGC相关（即，瓦尔 儿茶酚-O-甲基转移酶基因型的等位基因携带者）。最后，已显示较高的雌二醇水平 以促进人类与工作记忆相关的PFC功能。因此，我预测， 当雌二醇水平较低时，较高的担忧和较低的TGC之间的差异会更大。 在女性的月经周期中很高。这将是第一次对这些目标和意愿进行研究。 通过研究一种神经生物学上合理的机制， 焦虑会损害女性的工作记忆功能。从这个项目中产生的知识最终将 先进的焦虑理论模型以及焦虑的表达和影响所涉及的独特机制 女性对改善女性健康的焦虑。

PROJECT ABSTRACT Anxiety is the 6th leading cause of disability worldwide and is two times more prevalent in females than males. Importantly, anxiety is associated with reduced prefrontal cortex (PFC) function in areas critical for cognitive processes such as working memory. Although preclinical models have proposed complex interactive effects of anxiety and estradiol on working memory through modulations of prefrontal dopamine (DA), no research to date has examined the translational significance of these models in human females. To address this gap, this project aims to examine DA and estradiol’s effects on the relationship between worry, a core cognitive feature of anxiety, and neural oscillatory activity (i.e., theta-gamma coupling; TGC) indexing working memory function in females. The specific aims are to (1) establish the relationship between worry and TGC; (2) examine the role of basal DA in the relationship between worry and TGC; and (3) to examine the role of estradiol in the relationship between worry and TGC. Based on theoretical and empirical work demonstrating that worry reduces performance by placing an additional “load” on the cognitive system, I expect that worry will be related to reduced TGC, particularly under more difficult task conditions that place a high load on PFC function. To address Aim 2, the role of basal DA will be examined, given its critical role in working memory function. Specifically, DA demonstrates an inverted-U association with working memory function such that moderate levels of DA promote optimal working memory function whereas too much or too little DA is impairing. As such, I expect that higher worry will be associated with lower TGC in individuals with lower circulating DA (i.e., Val allele carriers of the catechol-o-methyltransferase genotype). Finally, higher estradiol levels have been shown to facilitate working memory-related PFC functioning in humans. I, therefore, predict that the association between higher worry and lower TGC will be larger when estradiol levels are low compared to when they are high in females across the menstrual cycle. This will be the first study of its kind to examine these aims and will significantly advance the research by examining a neurobiologically plausible mechanism through which anxiety impairs working memory function in females. Knowledge generated from this project will ultimately advance theoretical models of anxiety and the unique mechanisms involved in the expression and impact of anxiety in females for the improvement of women’s health.