Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology

我们的目标是评估情感调节策略是如何保护认知和情感功能的， 那些有可能患上与年龄有关的情绪和认知障碍的人。根据RFA MH-17 - 405， 对情感调节中成熟转变的研究往往得出不一致的结果， 支持影响监管的制度基本上尚未经过检验。在本申请中，我们建议密切 研究影响监管的两个成熟轨迹的动态和机制： 大脑中的β-淀粉样斑块。迄今为止，大多数努力都集中在与年龄有关的问题上， 化合价调节的变化（例如，与年龄相关的积极效应）。唤醒被认为是重要的， 但是对于老年人是如何积极地调节他们的唤醒状态，或者说近端和更长的- 这种调节尝试的长期后果是遭受与年龄有关的情绪变化的风险， 认知.我们团队最近的研究结果表明，那些为了一时的舒适而优化的人， 唤醒回避影响调节轨迹，而那些优化记忆和 注意力培养坚毅的轨迹（在服务于某个目标的过程中容忍暂时不愉快的能力 这需要努力，这往往是短暂的经验，作为一个不愉快的唤醒状态）。我们的工作还 这表明，情感调节与大脑两个区域的结构和连接有关。 核心网络：突出和默认模式网络。在老年人中，这些组织中的β淀粉样蛋白（A β）斑块 这两个网络是一个关键的病理-阿尔茨海默病（AD）的两个主要分子标志之一- 与认知能力下降、抑郁症和痴呆症的风险增加有关。与这些 考虑到观察，我们的团队将联合收割机（a）从正常的研究创新的理论和方法， 以情境为中心的影响调节的成熟变化，（B）结构、功能和分子脑 成像，以及（c）在一个大的五年时间内对空间和时间动态进行创新的计算建模 旨在研究唤醒调节与年龄变化和A β状态之间的关系。我们将 描述不同难度水平下以情境为中心的唤醒调节策略和认知努力 使用行为，经验和神经生物学水平的分析，无论是在行为实验室还是在 脑部扫描数据分析将涉及构建动态的时间轨迹， 每项任务表征觉醒回避和坚毅（即，在努力的服务中对高唤醒的容忍度）。 我们将描述和比较不同年龄段个体的觉醒回避和粗砂调节轨迹， 年龄（40 - 90岁）、A β状态、认知障碍和情绪障碍（区分两种 症状类型：痛苦（消极）和冷漠（缺乏努力或参与）。的调查结果 拟议的研究将用于开发一个长期项目，以确定如何的时间动态 情感调节预测情绪障碍和认知障碍的发展/成熟轨迹。

Our goal is to assess how affect regulation strategies are protective of cognitive and affective functioning in those who are at risk of suffering age-related disorders of mood and cognition. According to RFA MH-17-405, studies of maturational shifts in affect regulation often yield inconsistent findings and the neurobiological systems that support affect regulation remain largely untested. In this application, we propose to closely investigate the dynamics and mechanisms of two maturational trajectories that impact affect regulation: increasing age and beta-amyloid plaques within the brain. To date, most efforts have focused on age-related changes in valence regulation (e.g., the age-related positivity effect). Arousal is acknowledged as important, but very little is known about how older adults actively regulate their arousal states, or the proximal and longer- term consequences of such regulation attempts for risk of suffering age-related changes in mood and cognition. Recent findings from our team suggest that those who optimize for momentary comfort cultivate arousal-avoidance affect regulation trajectories, whereas those who optimize for mastery in memory and attention cultivate grit trajectories (the ability to tolerate momentary unpleasantness in the service of some goal that requires effort, which is often transiently experienced as an unpleasant aroused state). Our work also suggests that affect regulation is associated with both the structure and connectivity within two of the brain's core networks: the salience and default mode networks. In older adults, beta-amyloid (Aβ) plaques within these two networks are a key pathology—one of the two major molecular hallmarks of Alzheimer's disease (AD)— associated with elevated risk of cognitive decline, symptoms of depression, and dementia. With these observations in mind, our team will combine (a) innovative theory and methods from the study of normal maturational changes in situation-focused affect regulation, (b) structural, functional, and molecular brain imaging, and (c) innovative computational modeling of spatial and temporal dynamics in one large five year study designed to examine how arousal-regulation is associated with changing age and Aβ status. We will characterize situation-focused arousal regulation strategies and cognitive effort at various levels of difficulty using behavioral, experiential, and neurobiological levels of analysis, both in the behavioral lab and during brain scanning. Data analysis will involve constructing dynamic temporal trajectories across performance in each task to characterize arousal-avoidance and grit (i.e., tolerance of high arousal in the service of effort). We will characterize and compare arousal-avoiding and grit regulation trajectories in individuals who vary in age (from 40 to 90 years old), Aβ status, cognitive impairment, and mood symptomatology (distinguishing two types of symptoms: distress (negativity) and apathy (lack of effort or engagement). The findings from the proposed research will be used to develop a longer-term project to determine how the temporal dynamics of affect regulation predict developmental/maturational trajectories for mood disorders and cognitive impairment.