Exercise effects on neural circuits for CVD risk

摘要 项目3(柯克·埃里克森，PL) 运动对心血管疾病风险神经回路的影响 体力活动(PA)降低心血管疾病风险的机制尚不清楚。多行 然而，有证据表明，PA--尤其是有氧运动--对大脑健康和 大脑的可塑性。关键的是，运动可靠地影响大脑的区域是正在研究中的内脏控制区域 项目1和2.这些区域调节外周自主神经、神经内分泌和免疫的各个方面 与心血管疾病风险有关并受运动影响的生理学。因此，我们建议 整合(1)运动与心血管疾病风险，(2)运动与大脑可塑性的历史上分离的工作流程， (3)运动与压力、情感与生理控制。为此，我们提议进行为期12个月的干预。 其中150名中年和不活跃的成年人将被随机分配到(1)150分钟/周的适度运动(例如，快速运动 步行；N=75)或(2)轻伸展对照组，健康指导和社交活动类似于 治疗组(N=75)。我们将收集PS1-2的完整的神经成像测量：行为诱发 神经活动、脑灌注和功能连通性、白质完整性和灰质 3个波(基线、6个月、12个月)的形态。此外，我们使用动态心电监测和 首次采用生态瞬时评估(EMA)方法测试运动是否影响日常生活 应激生理和情感，以及这些影响是否部分通过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标来测试几个假设：目标1：确定神经生物学 运动和生物性心血管疾病危险因素的关系：(1A)身体-大脑假说：运动诱导的 心血管疾病风险的外周标记物(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)运动引起的某些功能和功能的变化 定义内脏控制回路的区域的结构特征。(1B)脑-体假说：运动诱导 决定内脏控制回路的区域的功能和结构特征在先于和部分地改变 解释(统计学中介)心血管疾病风险的自主神经和神经内分泌调节因子的相应变化 在神经调节下，包括压力反射敏感性、心率变异性和糖皮质激素 控制力。目的2：确定运动与压力和情感相关的心血管疾病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：运动将导致内脏控制区的变化 FMRI压力电池，这些变化将部分解释运动诱导的心血管压力的减少 日常生活中的反应性(与P的1和2协同作用)。(2B)心血管疾病风险的情感相关参数：运动会诱发 协同作用下功能磁共振情绪加工和调节范式参与的内脏控制区的变化 这些变化将在一定程度上解释运动对日常生活中测量的影响的改善 EMA和与P2协同作用的传统自我报告工具。这对公共卫生的意义 该项目旨在更准确地定义和细化神经生物学目标，以降低心血管疾病风险。

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.