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

项目摘要 焦虑是全球第六大致残原因，在女性中的患病率是男性的两倍。 重要的是，焦虑与认知关键区域的前额叶皮质(PFC)功能降低有关 工作记忆等过程。尽管临床前模型提出了复杂的相互作用效应 焦虑和雌二醇通过调节前额多巴胺(DA)对工作记忆的影响，没有研究表明 Date研究了这些模型在人类女性身上的翻译意义。为了解决这一差距，这 该项目旨在研究DA和雌二醇对焦虑之间的关系的影响，焦虑是一种核心认知特征 焦虑和神经振荡活动(即，theta-Gamma耦合；TGC)指示工作记忆功能 在雌性身上。具体目标是(1)建立焦虑与TGC之间的关系；(2)考察两者的作用 基础DA在焦虑和TGC之间的关系中的作用；以及(3)研究雌二醇在 焦虑与TGC的关系。基于理论和实证工作表明，担忧 通过给认知系统增加额外的“负担”来降低性能，我预计这种担忧将与 以降低TGC，特别是在对PFC功能施加高负载的更困难的任务条件下。至 在目标2中，鉴于基础DA在工作记忆功能中的关键作用，我们将研究它的作用。 具体地说，DA与工作记忆功能呈倒U形联系，从而适度 DA水平促进最佳工作记忆功能，而DA过多或过少都会损害工作记忆功能。因此， 我预计在循环DA较低(即Val)的个体中，较高的担忧将与较低的TGC相关 儿茶酚-O-甲基转移酶的等位基因携带者)。最后，研究表明，雌激素水平较高。 以促进人类与工作记忆相关的PFC功能。因此，我预测该协会 当雌二醇水平较低时，较高的焦虑和较低的TGC之间的差异将较大 在整个月经周期中女性的比例都很高。这将是第一次对这些目标和意愿进行研究。 通过检测一种神经生物学上看似合理的机制来显著推进研究 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 焦虑的先进理论模型和参与焦虑表达和影响的独特机制 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.