Neural and motivational mechanisms of age-related change in emotion regulation: Administrative Supplement

项目概述：在从中年到老年的过程中，健康的成年人通常会经历改善 在他们的情绪功能，如积极情绪的增加和管理情绪的专业知识。 然而，并不是每个人都表现出这些与年龄相关的改善，以及引起情绪变化的机制。 成年期的功能变化仍然知之甚少。这个项目的主要目标是检查 在正常老化中促进积极情绪发展的关键因素，并测试抑郁症是否 历史可能会作为一个关键特征个体差异标记来调节这一过程。为此，我们测试了我们提出的 成年期情绪调节的价值认知控制模型（VBCC-MERiAD）。VBCC-MERiAD 框架提出了一个新的见解：奖励动机和认知控制之间的相互作用， 在理解老年人情绪功能的规范轨迹方面发挥着核心作用，反之亦然， 为什么以及如何个人与抑郁症的历史可能会得到“偏离轨道”。我们的主要假设是情绪 调节（ER）能力依赖于额-纹状体回路的完整性（即，活动和连接之间的 外侧前额叶皮层和腹侧纹状体核），成功地利用奖励动机作为一个 参与认知控制的手段（即，更新和维护ER目标）。在三个具体目标中，我们将 使用多种方法表征中年和老年人（N=220，年龄35-75）的ER机制 设计涉及功能性神经影像测量、实验室行为评估和经验取样 方法，以确定神经和行为指标的动机和认知控制，预测每天 情绪功能，以及有抑郁史的个体的潜在失调。我们进一步建议， 丰富我们对ER年龄相关变化机制的理解， 评估临床前阿尔茨海默病（AD）和AD相关神经变性风险的能力， 使用基于血浆的生物标志物。通过与苏珊娜·辛德勒博士和布莱恩博士的新合作， 戈登，我们在华盛顿大学和奈特阿尔茨海默病研究中心的合作伙伴，我们将利用 最先进的方法，包括单分子阵列（Simoa）和质谱，全面 评估与淀粉样蛋白（APOE，β-淀粉样蛋白）、tau（ptau 181）和 神经变性（NfL，GFAP），以及解剖MRI生物标志物（例如，皮质厚度）。我们提出了一个 行政补充，为我们获取、处理和严格分析AD提供额外支持- 相关生物标志物数据。这一补充将大大提高我们项目的范围和影响， 使我们能够扩展我们的理解规范和功能失调的年龄相关的变化， 功能，不仅确定机制，促进积极的ER在成年后期，但也确定 未检测到的临床前AD在一定程度上缓和了这种作用。这样做，我们将奠定基础， 新的干预措施，以改善老年人和有抑郁症史的人的生活质量。

Project Summary: In the progression from middle to older-age, healthy adults typically experience improvements in their emotional functioning, such as increases in positive emotion and greater expertise in managing emotions. However, not everyone shows these age-related improvements, and the mechanisms that give rise to emotional functioning changes across adulthood are still poorly understood. The primary goal of this project is to examine the critical factors that promote positive emotional development in normative aging, and to test whether depression history might moderate this process as a key trait individual difference marker. To this end, we test our proposed Value-Based Cognitive Control Model of Emotion Regulation in ADulthood (VBCC-MERiAD). The VBCC-MERiAD framework suggests a novel insight: that interactions between reward motivation and cognitive control play a central role in understanding both the normative trajectory of emotional functioning in older adults, and conversely, why and how individuals with depression histories may get “off track”. Our primary hypothesis is that emotion regulation (ER) abilities rely upon the integrity of fronto-striatal circuitry (i.e., activity and connectivity between the lateral prefrontal cortex and nucleus accumbens / ventral striatum), to successfully utilize reward motivation as a means of engaging cognitive control (i.e., to update and maintain ER goals). Across three Specific Aims, we will characterize the mechanisms of ER in middle-aged and older adults (N=220, ages 35-75) using a multi-method design involving functional neuroimaging measures, laboratory behavioral assessments, and experience sampling methods, to identify the neural and behavioral indicators of motivation and cognitive control that predict daily emotional functioning, and potential dysregulation in individuals with depression history. We further propose to enrich our understanding of the mechanisms of age-related change in ER, by capitalizing on recent advances in the ability to assess risk of preclinical Alzheimer’s Disease (AD) and AD-related neurodegeneration through the use of blood plasma-based biomarkers. Through new collaborations with Dr. Suzanne Schindler and Dr. Brian Gordon, our partners at both Washington University, Knight Alzheimer’s Disease Research Center, we will utilize state-of-the-art methods, including single-molecule array (Simoa) and mass spectrometry, to comprehensively assess key blood-based biomarkers related to amyloid (APOE, beta-amyloid), tau (ptau181), and neurodegeneration (NfL, GFAP), as well as anatomical MRI biomarkers (e.g., cortical thickness). We propose an Administrative Supplement to provide additional support for us to acquire, process and rigorously analyze AD- related biomarker data. This Supplement will dramatically enhance the scope and impact of our project, by enabling us to extend our understanding of both normative and dysfunctional age-related change in emotional function, by not only identifying mechanisms that promote positive ER in late adulthood, but also determining the degree to which otherwise undetected preclinical AD moderates such effects. In so doing, we will lay the foundation for new interventions to improve quality of life for older adults and individuals with depression history.