Cross-training in human functional imaging for cognitive aging

描述（申请人提供）：我国老年人口不断增长；据预测，到2030年，每5个人中就有1个人的年龄将超过65岁。众所周知，衰老与多种功能衰退有关，可能导致独立性的丧失。认知能力的下降，尤其是学习和记忆能力的下降，早在人类50岁时就会出现。候选人Kathy Magnusson博士在利用Morris水迷宫研究啮齿动物与年龄相关的认知衰退的分子机制方面拥有超过23年的经验。这些研究清楚地证明了前额叶皮层在小鼠空间记忆衰退中与年龄相关的重要性，包括表明老年小鼠需要额外的前额叶区域来执行与年轻小鼠相同的空间学习任务。他的导师斯科特·莫法特（Scott Moffat）博士有证据表明，人类在衰老过程中前额叶皮层的变化与空间记忆有关。然而，最直接的功能性MRI测量并不是通过模拟水迷宫任务来完成的。NIH的OppNet已经确定，基础行为科学和社会科学的研究人员迫切需要在动物和人类研究方面进行交叉培训，以加强转化研究（RFA-DA-14-002）。候选人的直接目标是适应人类的虚拟水迷宫任务，更接近于小鼠任务，并学习人类的功能成像方法。长期目标是与导师建立长期合作关系，研究前额叶皮层在空间记忆中的作用，并开发与年龄相关的认知衰退的干预措施，这将从啮齿动物模型转化为人类。导师在人类认知测试，功能成像和复制人类认知衰老研究中的动物模型方面拥有丰富的经验。佐治亚理工学院拥有培训候选人和进行试点项目所需的所有设施和设备。候选人和导师的研究兴趣与导师所在机构的优良设施之间的协同作用使得

DESCRIPTION (provided by applicant): Our aged population is growing; by 2030 it is predicted that 1 out of every 5 people will be over the age of 65. It is well known that aging is associated with multiple functional declines that can lead to a loss of independence. Cognitive declines, particularly in learning and memory, are seen as early as the 5th decade of life in humans. The candidate, Dr. Kathy Magnusson, has over 23 years of experience in utilizing the Morris water maze to examine the molecular mechanisms underlying age-related cognitive decline in rodents. This body of research clearly demonstrates the importance of the prefrontal cortex in age-related declines in spatial memory in mice, including showing that older mice recruit additional prefrontal regions to perform the same spatial learning task as young. The mentor, Dr. Scott Moffat, has evidence that changes in the prefrontal cortex during aging in humans are involved in spatial memory. However, the most direct functional MRI measures were not done with a human analog of the water maze task. NIH's OppNet has identified a critical need for researchers in the basic behavioral and social sciences to be cross-trained in both animal and human research in order to enhance translational research (RFA-DA-14-002). The candidate's immediate goals are to adapt a virtual water maze task for humans to more closely resemble the mouse task and to learn functional imaging methods in humans. The long-term goals are to establish a long-term collaboration with the mentor to examine the role of prefrontal cortex in spatial memory and develop interventions into age-related cognitive decline that will translate from rodent models to humans. The mentor has extensive experience with human cognitive testing, functional imaging and replicating animal models in studies of human cognitive aging. Georgia Institute of Technology has all of the facilities and equipment necessary to train the candidate and conduct a pilot project. The synergy between the research interests of the candidate and mentor and the excellent facilities at the mentor's institution make this an ideal fit for accomplishing OppNet's goals to cross-train behavioral scientists and establish collaborations in cross-species research. Developing an animal model of brain region recruitments would help determine whether this is beneficial or harmful to memory in the elderly. Although both labs have evidence for prefrontal recruitment, the studies used different tasks. Our central hypothesis is that deficits in performance of a spatial long-term memory task during aging in humans are partially due to alterations in activation of prefrontal regions. This will be addressed by Aim 1: To identify activations and deactivations of brain regions that show relationships to spatial memory performance in young and old humans performing in a water maze task. These studies will provide important proof of principle that aged humans and rodents show similar recruitment of additional brain regions when performing a similar task. Being able to cross-experiment with both rodents and humans will enable us to better study mechanisms underlying this recruitment and design, test and apply interventions to improve cognitive flexibility into old age.