Longitudinal changes in white matter integrity predicting cognitive changes in reasoning and vocabulary abilities

白质完整性的纵向变化预测推理和词汇能力的认知变化

• 批准号: 9352744
• 负责人: YUNGLIN GAZES
• 金额: $ 12.46万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352744
• 关键词: Academic Medical Centers; Address; Adult; Age; Aging; Animal Experimentation; Animals; Award; Balsams; Behavior; Brain; Brain region; Cognition; Cognitive; Cognitive Science; Collection; Committee Members; Comorbidity; Comorbidity Index; Computer Systems; Crystallization; Data; Data Analyses; Data Collection; Data Storage and Retrieval; Diffusion Magnetic Resonance Imaging; Educational workshop; Elderly; Environment; Episodic memory; Exhibits; Exposure to; Follow-Up Studies; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Grant; Health; Individual; K-Series Research Career Programs; Knowledge; Laboratories; Learning; Link; Liquid substance; Longitudinal Studies; Maintenance; Measures; Medical; Mentored Research Scientist Development Award; Mentors; Modeling; Myelin; Neurobiology; Neurology; Neuropsychological Tests; Parietal; Participant; Pathway interactions; Performance; Prefrontal Cortex; Privatization; Process; Psychosocial Factor; Reading; Research; Research Design; Research Personnel; Research Training; Resistance; Resources; Solid; Speed; Statistical Data Interpretation; Stress; Structure; System; Targeted Research; Technical Expertise; Techniques; Testing; Time; Training; Training Programs; Universities; Vocabulary; Water; Writing; age group; age related; brain health; career; career development; cluster computing; cognitive ability; cognitive change; cognitive neuroscience; cognitive performance; design; follow-up; gaze; gray matter; high dimensionality; imaging study; improved; longitudinal analysis; meetings; multimodality; neural model; neurobiological mechanism; neuroimaging; neuron component; psychological aspect of aging; psychosocial; regional difference; relating to nervous system; responsible research conduct; skills; success; symposium; theories; visual motor; white matter; white matter change

Candidate: This candidate's long-term career goal is to become an independently funded researcher with an established laboratory conducting multimodal neuroimaging studies to examine the neurobiological mechanisms of aging. Dr. Gazes possesses strong technical skills and a solid background in the cognitive psychology of aging. Her path to independence would be accelerated through achieving short term goals: (1) Gain a comprehensive understanding of diffusion tensor imaging and T1 analysis, from basic preprocessing to sophisticated statistical techniques; (2) Become proficient in performing advanced multimodal neuroimaging analysis such as awFC, BSMac, and applying SVC to high-dimensional data; (3) Design and execute a longitudinal imaging study; implement advanced longitudinal statistical analysis techniques; (4) Receive training in administering and analyzing neuropsychological testing; (5) Learn theories and current state of knowledge in the neurobiology of aging; (6) Understand the inter-relationships among medical comorbidity, health, and psychosocial factors with neural and cognitive variables; (7) Gain exposure to multigradient T2 relaxometry and animal research practices; and (8) Receive extensive training in the responsible conduct of research. These goals will be accomplished with the support of the mentoring committee consisting of Dr. DuBois Bowman as my primary mentor, Dr. Yaakov Stern as a co-mentor, and Drs. Dongrong Xu, Christian Habeck, Edward Huey, and Peter Balsam as consultants. The plan for accomplishing the short term goals consists of direct readings and weekly meeting with Dr. Bowman, applying advanced techniques on collected data under my mentoring committee's guidance, attending courses, workshops, seminars, and conferences, independent collection of longitudinal data, and applying for an R01 grant award. Research: Performance on a number of cognitive abilities such as reasoning has been shown to decline in older adulthood. However, factual knowledge such as vocabulary remains relatively intact, and actually increases with age. If aging is a brain-wide phenomenon, one would expect cognitive abilities to worsen with aging. The maintenance of vocabulary and other crystallized knowledge is surprising given the widespread neural decline commonly associated with aging. Understanding how such divergent phenomenon can be supported by a single neural system offers exciting translational potential. Examining the structural/axonal and functional differences between the two cognitive domains with divergent maturational processes may reveal the differential mechanisms for aging decline versus aging maintenance. In the following proposal, Dr. Gazes will use cross-sectional and longitudinal study designed to test the hypothesis that the functional network of brain regions and the integrity of gray and white matter associated with vocabulary are well maintained with aging, while substantial decline occurs for the functional and gray and white matter networks associated with reasoning. Cross-sectionally, she will use fMRI and DTI from 375 participants across six decades to compare the age-related differences in the neural systems underlying the reasoning and vocabulary abilities. To understand how these domain's neural systems change with age, and as training for her career development, she will conduct a 4-year follow-up study on 90 of the 375 participants by collecting fMRI, DTI, T1, and cognitive performance on reasoning and vocabulary abilities. This longitudinal data will allow her to: (1) determine if the neural system (gray and white matter and functional connectivity) underlying the reasoning ability declines more rapidly than the neural system underlying the vocabulary ability and (2) perform a comprehensive examination of the factors (neural, health, and psychosocial) that predict cognitive changes in reasoning and in vocabulary. Success of this grant will provide clues towards future targeted research into the aging mechanism. Environment: The research and training will take place at Columbia University Medical Center within the Cognitive Neuroscience Division of the Neurology department. All of the committee members are on campus and available on a regular basis. Dr. Gazes will have access to a state-of-the-art cluster computing system connected to a high capacity data storage system, along with private office space dedicated to her research. The university provides a large number of resources for career development including grant writing workshops and career development and advisement. Through the proposed longitudinal data collection and analyses, training for career development will provide Dr. Gazes with a comprehensive set of research skills essential for independence including study design and administration, advanced neuroimaging analytical techniques for more robust modeling of brain to behavior relationships, and more in-depth knowledge of neuroimage processing with a special emphasis on DTI data. With the protected time provided by this career development award, I will be able to successfully transition into an independent researcher in the cognitive neuroscience of aging.

候选人：这位候选人的长期职业目标是成为一名拥有独立资助的研究员 既定实验室进行多模式神经影像学研究，以检查神经生物学 衰老机制。凝视博士具有强大的技术技能和认知能力的坚实背景 衰老心理学。她的独立之路将通过实现短期目标加速：（1） 从基本的预处理到扩散张量成像和T1分析的全面了解 精致的统计技术； （2）熟练地执行高级多模式神经影像学 分析（例如AWFC，BSMAC）和将SVC应用于高维数据； （3）设计和执行 纵向成像研究；实施先进的纵向统计分析技术； （4）收到 在管理和分析神经心理学测试方面的培训； （5）学习理论和当前状态 衰老神经生物学知识； （6）了解医疗合并症之间的关系， 健康和神经和认知变量的社会心理因素； （7）获取多移动T2的暴露 放松和动物研究实践； （8）接受负责任的广泛培训 研究。这些目标将在指导委员会的支持下实现。 杜波依斯·鲍曼（Dubois Bowman）是我的主要导师Yaakov Stern博士担任院长，又是Drs。 Dongrong Xu，基督徒 Habeck，Edward Huey和Peter Balsam担任顾问。实现短期目标的计划 包括直接阅读和每周与鲍曼博士的会议，应用高级技术 在我的指导委员会指导下的数据，参加课程，研讨会，研讨会和会议， 独立收集纵向数据，并申请R01赠款奖。 研究：已经证明了许多认知能力（例如推理）的表现会下降 较早的成年。但是，诸如词汇之类的事实知识仍然相对完整，实际上 随着年龄的增长而增加。如果衰老是一种大脑的现象，人们会期望认知能力会随着 老化。鉴于广泛的范围，词汇和其他结晶知识的维护令人惊讶 神经下降通常与衰老有关。了解这种不同的现象如何 在单个神经系统的支持下，具有令人兴奋的翻译潜力。检查结构/轴突 与成熟过程不同的两个认知领域之间的功能差异可能 揭示衰老下降与维持衰老的差异机制。在以下提案中，博士 凝视将使用横断面和纵向研究，旨在检验功能性的假设 大脑区域网络以及与词汇相关的灰色和白质的完整性很好 保持衰老，虽然功能和灰色和白色物质网络发生大幅下降 与推理有关。在横截面上，她将使用375名参与者的fMRI和DTI，六个 比较推理和词汇层面的神经系统中与年龄相关的差异的数十年 能力。了解这些领域的神经系统如何随着年龄的增长而变化，作为她职业生涯的培训 开发，她将通过收集fMRI，DTI，对375名参与者中的90名进行4年的随访研究 T1，以及推理和词汇能力的认知表现。这些纵向数据将使她能够： （1）确定神经系统（灰色和白色物质以及功能连接）是否存在 推理能力比词汇能力的基础神经系统更快地下降，并且（2） 对预测认知的因素（神经，健康和社会心理）进行全面检查 推理和词汇的变化。这笔赠款的成功将为未来的目标提供线索 研究衰老机制。 环境：研究和培训将在哥伦比亚大学医学中心举行 神经科学系的认知神经科学系。所有委员会成员都在校园里 并定期使用。凝视博士将可以使用最先进的集群计算系统 连接到高容量数据存储系统，以及专门研究她的研究的私人办公空间。这 大学为职业发展提供了大量资源，包括赠款写作研讨会和 职业发展和建议。 通过拟议的纵向数据收集和分析，对职业发展培训将提供 凝视博士，具有一套全面的研究技能，包括研究设计和 给药，高级神经影像学分析技术，以对大脑进行更强大的建模到行为 关系，以及对神经图像处理的更深入的知识，并特别强调DTI数据。 随着该职业发展奖提供的保护时间，我将能够成功过渡 成为衰老认知神经科学的独立研究人员。