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如何保护认知和情感功能 那些有遭受与年龄相关的情绪和认知障碍的风险的人。根据RFA MH-17-405， 对情感调节的成熟转变的研究经常产生不一致的结果和神经生物学 支持影响监管的系统在很大程度上仍未经过考验。在本应用程序中，我们建议密切关注 研究影响监管的两个成熟轨迹的动力学和机制： 年龄增加和大脑中的β-淀粉样斑块。到目前为止，大多数努力都集中在与年龄有关的方面 价态调节的变化(例如，与年龄相关的积极效应)。唤醒被认为是重要的， 但关于老年人如何积极调节他们的觉醒状态，或者是近端和更长时间的觉醒状态，人们知之甚少。 这种规定的长期后果是试图承受与年龄相关的情绪和情绪变化的风险 认知力。我们团队最近的发现表明，那些为了暂时的舒适感而进行优化的人 唤醒-回避影响调节轨迹，而那些优化记忆和控制的人 注意力培养坚韧的轨迹(为了某个目标而容忍暂时的不愉快的能力 这需要努力，这通常被认为是一种令人不快的唤醒状态)。我们的工作也 表明情绪调节与两个大脑的结构和连通性有关 核心网络：显著模式网络和默认模式网络。在老年人中，这些区域内的β-淀粉样蛋白(Aβ)斑块 两个网络是一个关键的病理--阿尔茨海默病(AD)的两大分子特征之一-- 与认知衰退、抑郁症状和痴呆症的风险增加有关。有了这些 考虑到观察，我们的团队将结合(A)研究正常的创新理论和方法 关注情境的成熟变化影响调节，(B)结构、功能和分子脑 成像，以及(C)一个大型五年的空间和时间动力学创新计算模型 一项旨在研究唤醒调节与年龄和Aβ状态变化之间的关系的研究。我们会 描述不同难度水平下的情景唤醒调节策略和认知努力 在行为实验室和过程中使用行为、经验和神经生物学水平的分析 脑部扫描。数据分析将涉及构建跨性能的动态时间轨迹 每项任务的特点是唤醒--回避和坚韧(即，对努力服务中的高度唤醒的容忍)。 我们将描述和比较不同性别个体的觉醒回避和意志调节轨迹。 年龄(从40岁到90岁)、Aβ状态、认知障碍和情绪症状(区分两种 症状类型：痛苦(消极)和冷漠(缺乏努力或投入)。调查结果来自于 拟议的研究将被用来开发一个更长期的项目，以确定 情绪调节预测情绪障碍和认知障碍的发育/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.