Exploring real-time alterations in cerebral perfusion, BOLD signal, and cognition during physical activity

摘要 衰老与普遍的神经和认知衰退有关，贫穷会进一步加速衰老 心肺(CR)功能。心脏和呼吸功能与大脑和认知功能的交集 研究表明，血管功能障碍是衰老的一个主要组成部分，这进一步突显了衰老。 相关的认知能力下降，可能是由脑血管反应性的改变所支撑的。重要的是 心脏、血管和呼吸功能根据生理需求动态变化- 标准脑成像方法无法捕捉到的变化，当受试者通常经历 躺着不动时做磁共振成像(MRI)。因此，一种更敏感的方法是使用 当心脏、血管和呼吸功能被征税时，体力活动期间的神经成像。现存的 使用体力活动来引发CR挑战的研究实现了缺乏空间的成像方法 CR挑战后检查区域变化或获取影像数据的分辨率，此时心脏 心率和呼吸已回到基线，因此未能探测到可能是 对年龄相关的脑血流动力学变化敏感。在这里，我们建议阐明神经血管 通过实施一种新颖的、自然主义的CR挑战来实现与年龄相关的衰退机制 同时进行功能磁共振成像(FMRI)。我们使用了一种独特的“心脏起搏器”装置，一种类似楼梯的装置 连接到核磁共振工作台上的一件设备。通过控制身体活动的强度 通过功能磁共振成像，我们能够实时观察CR工作量对神经生理学的影响。这 创新允许在体力活动期间评估脑血流动力学，其方式类似于 心脏负荷试验(要求患者在跑步机上以越来越大的强度行走/跑步)被用于临床 确定静息状态下不存在的心脏异常，只有在患者处于睡眠状态时才能识别 心肺高压。在这项提案中，25名年轻人和25名老年人将接受认知测试，最高 运动中的心肺运动试验(CPET)和磁共振成像。具体目标1侧重于 阐明(血氧水平依赖)体力活动中BOLD反应的年龄相关变化 活动。在功能磁共振成像期间，将实施块设计CR挑战。探索下游大脑 锻炼的好处，我们还将获得CR挑战前后的动脉自旋标记(ASL)MRI数据 检查运动刺激后脑血流量是否增加。特定目标2将 研究认知障碍挑战中的大胆反应是否与认知表现相关 年轻人和老年人。研究脑部区域性改变的研究范式的发展 体力活动期间的血流动力学，使CR系统处于压力之下，具有潜在的作用 作为神经和认知功能衰退风险人群的生物标志物。

ABSTRACT Aging is associated with pervasive neural and cognitive decline, which is further accelerated by poor cardiorespiratory (CR) function. This intersection of cardiac and respiratory function with brain and cognitive aging is further highlighted by research demonstrating that vascular dysfunction is a major component of age- associated cognitive decline, likely underpinned by alterations in cerebrovascular reactivity. Importantly, cardiac, vascular, and respiratory functions change dynamically in response to physiological demands – changes that are not captured by the standard brain imaging approach, when subjects typically undergo Magnetic Resonance Imaging (MRI) while lying still. A more sensitive approach, therefore, is to use neuroimaging during physical activity, when cardiac, vascular, and respiratory functions are taxed. Extant studies using physical activity to elicit a CR challenge implement imaging methods that lack the spatial resolution to examine regional changes or acquire imaging data after the CR challenge, by which time heart rate and respiration have returned to baseline, thereby failing to probe a critical period that may be most sensitive to age-related changes in cerebral hemodynamics. Here we propose to elucidate neurovascular mechanisms of age-associated decline through the implementation of a novel, naturalistic, CR challenge during simultaneous functional MRI (fMRI). We do so using a unique “cardiostepper” device, a Stairmaster-like piece of equipment that attaches to the MRI table. By manipulating the intensity of physical activity during fMRI, we are able to observe real-time changes in neurophysiology as a function of CR workload. This innovation allows for the assessment of cerebral hemodynamics during physical activity in a similar way that a ‘cardiac stress test’ (asking patients to walk/run on a treadmill at increasing intensity) is used clinically to identify cardiac abnormalities that are not present at rest and only identifiable when the patient is under cardiopulmonary duress. In this proposal, 25 young and 25 older adults will undergo cognitive testing, maximal cardiopulmonary exercise testing (CPET), and MRI during exercise challenge. Specific Aim 1 is focused on the elucidation of age-related changes in (blood oxygenation level dependent) BOLD response during physical activity. During fMRI, a block-design CR challenge will be implemented. To explore downstream cerebral benefits of exercise, we will also acquire arterial spin labeling (ASL) MRI data pre- and post-CR challenge to examine whether cerebral blood flow is augmented subsequent to an exercise stimulus. Specific Aim 2 will examine whether the BOLD response during CR challenge is correlated with cognitive performance among young and older adults. The development of a paradigm to examine regionally-specific alterations in cerebral hemodynamics during physical activity, which places the CR system under duress, has the potential to serve as a biomarker for those at risk for neural and cognitive decline.