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独立资助的研究员，拥有 建立实验室，进行多模式神经成像研究，以检查神经生物学 衰老的机制。考斯博士拥有很强的技术技能和扎实的认知背景 衰老心理学。通过实现短期目标，她的独立之路将加快：(1) 全面了解扩散张量成像和T1分析，从基本的预处理到 成熟的统计技术；(2)熟练执行先进的多模式神经成像 分析AWFC、BSMac，并将SVC应用于高维数据；(3)设计并执行 纵向成像研究；实施先进的纵向统计分析技术；(4)接收 进行神经心理测试管理和分析的培训；(5)学习理论和现状 了解衰老的神经生物学知识；(6)了解医学共病之间的相互关系， 健康、心理社会因素与神经和认知变量；(7)暴露于多梯度T2 松弛测量和动物研究实践；以及(8)接受负责任的行为方面的广泛培训 研究。这些目标将在指导委员会的支持下实现。 杜布瓦·鲍曼是我的主要导师，雅科夫·斯特恩博士是我的共同导师，克里斯蒂安·徐东荣博士是 哈贝克、爱德华·休伊和彼得·巴尔萨姆担任顾问。完成短期目标的计划 包括直接阅读和与鲍曼博士的每周会议，应用先进的技术收集 在我的指导委员会的指导下，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资助奖。 研究：在许多认知能力方面，如推理能力的表现已显示出在 成年年龄较大。然而，词汇等事实知识仍然相对完整，而且实际上 随年龄增长。如果衰老是一种全脑现象，人们预计认知能力会随着年龄的增长而恶化。 衰老。保持词汇和其他具体化的知识是令人惊讶的，因为 神经衰弱通常与衰老有关。理解这种不同的现象是如何 在单一神经系统的支持下，提供了令人兴奋的翻译潜力。检查结构/轴突 而两个成熟过程不同的认知域之间的功能差异可能 揭示老化衰退与老化维护的不同机制。在下面的提案中，Dr。 Gazes将使用横断面和纵向研究来测试这一假设 大脑区域网络和与词汇相关的灰质和白质的完整性是很好的 随着年龄的增长而维持，而功能以及灰质和白质网络出现显著下降 与推理相关的。在横断面上，她将使用fMRI和DTI，来自6个国家的375名参与者 几十年来比较推理和词汇背后的神经系统与年龄相关的差异 超能力。了解这些领域的神经系统如何随着年龄的变化而变化，并作为她职业生涯的训练 她将对375名参与者中的90名进行为期4年的跟踪研究，收集功能磁共振成像、DTI、 T1，以及对推理和词汇能力的认知表现。这一纵向数据将使她能够： (1)确定神经系统(灰质和白质以及功能连通性)是否 推理能力的下降比词汇能力背后的神经系统下降得更快。 对预测认知的因素(神经、健康和心理社会)进行全面检查 推理和词汇方面的变化。这笔赠款的成功将为未来的目标提供线索 对衰老机理进行研究。 环境：研究和培训将在哥伦比亚大学医学中心进行 神经内科认知神经科学部。所有的委员都在校园里 并定期可用。考斯博士将有权使用最先进的集群计算系统 连接到一个高容量的数据存储系统，以及专门用于研究的私人办公室。这个 大学为职业发展提供大量资源，包括拨款撰写工作坊和 职业发展和咨询。 通过拟议的纵向数据收集和分析，职业发展培训将提供 博士拥有一套对独立至关重要的全面的研究技能，包括研究设计和 管理，高级神经成像分析技术，可更稳健地对大脑行为进行建模 关系，以及更深入的神经图像处理知识，特别强调DTI数据。 有了这个职业发展奖提供的保障时间，我将能够成功地过渡 成为认知神经科学领域的独立研究人员。