Cross-training in human functional imaging for cognitive aging

认知衰老的人体功能成像交叉训练

• 批准号: 8785632
• 负责人: KATHY R MAGNUSSON
• 金额: $ 13.98万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8785632
• 关键词: Address; Affect; Age; Age-associated memory impairment; Aging; Aging-Related Process; Animal Experimentation; Animal Model; Animals; Award; Behavioral; Behavioral Research; Biological Markers; Brain; Brain region; Censuses; Cognitive; Cognitive aging; Collaborations; Early Intervention; Elderly; Equipment; Etiology; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hippocampus (Brain); Human; Impaired cognition; Individual; Institutes; Institution; Intervention; Investigation; K-18 conjugate; K-Series Research Career Programs; Lead; Learning; Left; Life; Literature; Longevity; Measures; Memory; Mentors; Methods; Modeling; Molecular; Mus; Neurosciences; Performance; Phase; Pilot Projects; Population; Prefrontal Cortex; Quality of life; Records; Recruitment Activity; Research; Research Methodology; Research Personnel; Resources; Right-On; Rodent; Rodent Model; Role; Scientist; Side; Technology; Testing; Training; Translating; Translational Research; Water; age related; aged; analog; behavior measurement; behavioral/social science; career; career development; design; experience; flexibility; functional decline; human male; human subject; imaging modality; improved; interest; long term memory; memory acquisition; morris water maze; mouse model; neuroimaging; novel; programs; psychologic; public health relevance; research study; response; therapy design; translational approach; virtual; way finding; young adult

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.

描述（由申请人提供）：我们的老年人口正在增长;到2030年，预计每5人中就有1人超过65岁。众所周知，衰老与多种功能衰退有关，这些功能衰退可能导致独立性丧失。认知能力下降，特别是在学习和记忆方面，早在人类生命的第五个十年就可以看到。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能力下降的分子机制方面拥有超过23年的经验。这项研究清楚地证明了前额叶皮层在小鼠空间记忆力与年龄相关的下降中的重要性，包括显示老年小鼠招募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。导师斯科特·莫法特博士有证据表明，人类衰老过程中前额皮质的变化与空间记忆有关。然而，最直接的功能性MRI测量并不是用人类模拟水迷宫任务来完成的。NIH的OppNet已经确定了基础行为和社会科学研究人员在动物和人类研究中进行交叉培训的迫切需要，以加强转化研究（RFA-DA-14-002）。候选人的直接目标是使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，以研究前额叶皮层在空间记忆中的作用，并开发干预措施，以应对与年龄相关的认知衰退，并将其从啮齿动物模型转化为人类。导师在人类认知测试、功能成像和人类认知老化研究中复制动物模型方面拥有丰富的经验。格鲁吉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之间的协同作用以及导师所在机构的优良设施， 这是实现OppNet目标的理想选择，该目标是交叉培训行为科学家并建立跨物种研究的合作。开发一个大脑区域重新招募的动物模型将有助于确定这对老年人的记忆是有益还是有害。虽然两个实验室都有前额叶募集的证据，但研究使用了不同的任务。我们的中心假设是，在人类衰老过程中的空间长期记忆任务的性能赤字部分是由于前额叶区域的激活改变。这将通过目标1来解决：确定在水迷宫任务中执行的年轻人和老年人中显示与空间记忆表现相关的大脑区域的激活和失活。这些研究将提供重要的原则证据，即老年人和啮齿动物在执行类似任务时显示出类似的额外大脑区域招募。能够与啮齿动物和人类进行交叉实验将使我们能够更好地研究这种招募的机制，并设计、测试和应用干预措施，以提高老年人的认知灵活性。

项目成果

The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning.

• DOI: 10.1037/bne0000219
• 发表时间: 2017-12
• 期刊: Behavioral neuroscience
• 影响因子: 1.9
• 作者: Zhong JY;Magnusson KR;Swarts ME;Clendinen CA;Reynolds NC;Moffat SD
• 通讯作者: Moffat SD

Age-related differences in brain activations during spatial memory formation in a well-learned virtual Morris water maze (vMWM) task.

在充分学习的虚拟莫里斯水迷宫（vMWM）任务中，空间记忆形成过程中大脑激活的年龄相关差异。

• DOI: 10.1016/j.neuroimage.2019.116069
• 发表时间: 2019
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Reynolds,NadjalisseC;Zhong,JimmyY;Clendinen,CheritaA;Moffat,ScottD;Magnusson,KathyR
• 通讯作者: Magnusson,KathyR