Aerobic Exercise, Neurotrophins, and fMRI of Hippocampal Function and Structure

描述（由申请人提供）：本途径资助中提出的研究确定并寻求填补当前有关人类有氧运动与心血管健康以及功能性和结构性大脑健康之间关系的知识空白。拟议的人类神经影像研究建立在大量现有动物研究的基础上，旨在将这项工作扩展到人类。该候选人有兴趣建立一个独立的研究生涯，研究有氧运动和心血管健康对人类整个生命周期认知和大脑健康的影响。该候选人过去和当前的研究包括功能磁共振成像（fMRI）研究工作记忆和长期记忆之间的相互作用以及内侧颞叶（包括海马体）和前额叶皮层在工作记忆中的作用。该提案的总体目标是让候选人为转化认知神经科学领域的独立科学家的职业生涯做好准备。导师包括记忆认知神经影像学专家 Chantal E. Stern 博士（哲学博士）、运动生理学和神经康复教授 Robert C. Wagenaar 博士（因其在运动障碍方面的研究而闻名）、认知和行为神经学专家 Andrew E. Budson 博士（因其在阿尔茨海默病认知功能障碍和记忆功能障碍方面的研究而闻名）以及 Alice 博士克罗宁-哥伦布博士临床心理学教授和衰老神经心理学专家。该研究计划的目标是 1) 使用两项记忆任务和功能磁共振成像（具体目标 #1），在人类中建立有氧运动、心血管健康、海马依赖性记忆的功能性神经解剖学和神经营养蛋白（脑源性神经营养因子 (BDNF)）之间的联系（具体目标 #1），2) 调查健康年轻人和老年人久坐的 12 周有氧运动干预是否与记忆任务表现的改善、血清浓度的增加有关使用功能磁共振成像和测试前-测试后随机对照组设计（具体目标＃2）来检测 BDNF 水平和增强任务相关海马活动（具体目标＃2），以及 3）使用结构 MRI 和形态测量方法研究对健康年轻和老年久坐个体进行相同的有氧运动干预是否会导致海马和/或海马亚区体积增加以及其他大脑区域的皮质厚度增加。候选人将获得运动生理学和神经康复、老年神经病学、临床神经心理学评估、结构 MRI 图像的形态测量分析以及临床试验设计方面的基本培训。该项目将使候选人能够建立一个外部资助的转化认知神经科学研究项目。有氧运动可能是一种有效且低成本的干预措施，不仅可以促进身体健康，还可以促进大脑健康，从而实现健康老龄化。定期进行中等强度的有氧运动可能在整个生命周期中具有神经保护作用。 公共卫生相关性：定期进行中等强度的有氧运动可能是健康老龄化的一种有效且低成本的干预措施，不仅可以促进身体健康，还可以促进大脑健康，并且可能在整个生命周期中具有神经保护作用。运动对大脑的这些影响已在动物模型中进行了广泛研究，但尚未在人类中进行研究。这组研究旨在研究健康年轻人和老年人的衰老、运动和大脑之间的关系。

DESCRIPTION (provided by applicant): The research proposed in this Pathways grant identifies and seeks to fill a current gap in knowledge regarding the relationship between aerobic exercise and cardiovascular fitness and functional and structural brain health in humans. The proposed human neuroimaging studies build upon a large body of existing animal research, and aim to extend this work to humans. The candidate is interested in establishing an independent research career in which she can study the effects of aerobic exercise and cardiovascular fitness on cognition and brain health in humans across the lifespan. The candidate's past and current research has included functional Magnetic Resonance Imaging (fMRI) studies of interactions between working memory and long-term memory and the role of the medial temporal lobes (including the hippocampus) and prefrontal cortex in working memory. The overall goal of this proposal is to prepare the candidate for a career as an independent scientist in translational cognitive neuroscience. Mentors include Dr. Chantal E. Stern, D.Phil., an expert in the cognitive neuroimaging of memory, Dr. Robert C. Wagenaar, Ph.D., a professor of exercise physiology and neurorehabilitation who is known for his work on movement disorders, Dr. Andrew E. Budson, M.D., an expert in cognitive and behavioral neurology, who is known for his work on cognitive dysfunction and memory dysfunction in Alzheimer's Disease, and Dr. Alice Cronin-Golomb, Ph.D. a professor of clinical psychology and an expert in the neuropsychology of aging. The goals of the research plan are to 1) establish a link between aerobic exercise, cardiovascular fitness, the functional neuroanatomy of hippocampal-dependent memory, and a neurotrophin, the Brain-Derived Neurotrophic Factor (BDNF) in humans using two memory tasks and fMRI (Specific Aim #1), 2) investigate whether a 12-week aerobic exercise intervention in healthy young and older sedentary adults is associated with an improvement in memory task performance, increased serum BDNF levels, and enhanced task-related hippocampal activity using fMRI and a pretest-posttest randomized control group design (Specific Aim #2), and 3) investigate whether the same aerobic exercise intervention in healthy young and older sedentary individuals results in increased volume in the hippocampus and/or hippocampal subfields, and cortical thickness in other brain areas using structural MRI and morphometric methods. The candidate will acquire essential training in exercise physiology and neurorehabilitation, geriatric neurology, clinical neuropsychological assessment, morphometric analyses of structural MRI images, and in clinical trial design. The project will enable the candidate to establish an externally funded research program in translational cognitive neuroscience. Aerobic exercise may be an effective and low-cost intervention resulting in healthy aging by promoting not only physical health, but also brain health. Regular moderate intensity aerobic exercise may have neuroprotective effects throughout the lifespan. PUBLIC HEALTH RELEVANCE: Regular moderate intensity aerobic exercise may be an effective and low-cost intervention for healthy aging by promoting not only physical health, but also brain health, and may have neuroprotective effects throughout the lifespan. These effects of exercise on the brain have been studied extensively in animal models, but not in humans. This set of studies aims to examine the relationship between aging, exercise, and the brain in healthy young and older individuals.