Exercise effects on neural circuits for CVD risk

摘要 项目3（Kirk Erickson，PL） 运动对CVD风险神经回路的影响 体力活动（PA）降低CVD风险的机制尚不清楚。多行 然而，有证据表明，PA -特别是有氧运动-对大脑健康产生有益的影响， 大脑可塑性至关重要的是，受运动影响的大脑区域是正在研究的内脏控制区域， 项目（PS）1和2。这些区域调节外周自主神经、神经内分泌和免疫功能。 生理学参与赋予心血管疾病的风险和有利的影响，运动。因此，我们建议 整合历史上独立的工作线（1）运动和CVD风险，（2）运动和大脑可塑性， （3）运动与压力、情感和生理控制。为此，我们建议进行为期12个月的干预 其中将150名中年和不活动的成年人随机分为（1）150分钟/周的适度运动（例如，轻快 步行; N=75）或（2）轻度拉伸对照组，具有类似的健康指导和社会互动， 治疗组75例。我们将收集PS 1-2不可或缺的神经影像学指标：行为诱发 神经活动、脑灌注和功能连接、白色物质完整性和灰质 3个波时的形态学（基线、6个月、12个月）。此外，我们使用动态CV监测， 生态瞬时评估（EMA）方法首次测试运动是否影响日常生活 压力生理学和影响，以及这些影响是否部分由内脏控制区的变化来解释。 我们的设计允许我们通过以下目的来测试几个假设：目的1：确定神经生物学 运动和生物学CVD危险因素的关系：（1A）身体-大脑假说：运动引起的 CVD风险的外周标志物（例如，胰岛素抵抗、心肺功能、外周血管功能） 将先于并部分解释（统计中介）一些运动引起的功能和 定义内脏控制回路的区域的结构特征。(1B)脑-体假说：脑损伤诱导 定义内脏控制回路的区域的功能和结构特征的变化先于和部分地 解释（统计学介导）CVD风险的自主神经和神经内分泌介质的后续变化 包括压力反射敏感性、心率变异性和糖皮质激素 控制目的2：确定运动与压力和情感相关的CVD危险因素的神经生物学：（2A） 心血管疾病风险的应激相关参数：运动会引起由运动员参与的内脏控制区的变化。 这些变化将部分解释运动引起的心血管压力降低 日常生活中的反应性（与P 1和2的协同作用）。(2B)心血管疾病风险的影响相关参数：运动会诱导 功能磁共振成像情绪加工和调节协同模式对内脏控制区的影响 这些变化将部分解释日常生活中测量的运动引起的情感改善 通过EMA和传统的自我报告工具与P2协同作用。这对公众健康的重要性 该项目旨在更精确地定义和完善神经生物学靶点，以降低CVD风险。

ABSTRACT Project 3 (Kirk Erickson, PL) Exercise effects on neural circuits for CVD risk The mechanisms by which physical activity (PA) may reduce CVD risk remain unclear. Multiple lines of evidence, however, show that PA – particularly aerobic exercise – exerts beneficial effects on brain health and brain plasticity. Critically, the brain areas reliably affected by exercise are visceral control areas under study in Projects (Ps) 1 and 2. These areas regulate aspects of peripheral autonomic, neuroendocrine, and immune physiology that are involved in conferring CVD risk and favorably affected by exercise. Accordingly, we propose to integrate historically separate lines of work on (1) exercise and CVD risk, (2) exercise and brain plasticity, and (3) exercise and stress, affect, and physiological control. To this end, we propose a 12-month intervention in which 150 midlife and inactive adults will be randomized to (1) 150 min/wk of moderate exercise (e.g., brisk walking; N=75) or (2) a light stretching control group with similar health instruction and social interaction as the treatment group (N=75). We will collect neuroimaging measures integral to Ps 1-2: behaviorally-evoked neural activity, cerebral perfusion and functional connectivity, white matter integrity, and gray matter morphology at 3 waves (baseline, 6-months, 12-months). Moreover, we use ambulatory CV monitoring and ecological momentary assessment (EMA) methods for the first time to test whether exercise impacts daily life stress physiology and affect, and whether these effects are partly explained by changes to visceral control areas. Our design allows us to test several hypotheses by the following Aims: Aim 1: To determine the neurobiology of exercise and biological CVD risk factors: (1A) Body-to-Brain hypothesis: Exercise-induced changes in peripheral markers of CVD risk (e.g., insulin resistance, cardiorespiratory fitness, peripheral vascular function) will precede and partly explain (statistically mediate) some of the exercise-induced changes in functional and structural features of areas defining visceral control circuits. (1B) Brain-to-Body hypothesis: Exercise-induced changes in functional and structural features of areas defining visceral control circuits precede and partly explain (statistically mediate) consequent changes in autonomic and neuroendocrine mediators of CVD risk that are under neural regulation, including baroreflex sensitivity, heart rate variability, and glucocorticoid control. Aim 2: To determine the neurobiology of exercise and stress- and affect-related CVD risk factors: (2A) Stress-related parameters of CVD risk: Exercise will induce changes in visceral control areas engaged by an fMRI stress battery, and these changes will partly explain exercise-induced reductions in cardiovascular stress reactivity in daily life (synergy with P's 1 & 2). (2B) Affect-related parameters of CVD risk: Exercise will induce changes in visceral control areas engaged by an fMRI emotion processing and regulation paradigm in synergy with P1, and these changes will partly explain exercise-induced improvements in affect measured in daily life by EMA and by conventional self-report instruments in synergy with P2. The public health significance of this Project is that it is designed to more precisely define and refine neurobiological targets to reduce CVD risk.