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

候选人：该候选人的长期职业目标是成为一名独立资助的研究人员， 建立实验室进行多模式神经成像研究以检查神经生物学 老化的机制。Gazes博士拥有强大的技术技能和坚实的认知背景， 衰老心理学她的独立之路将通过实现短期目标来加速：（1） 全面了解扩散张量成像和T1分析，从基本预处理到 复杂的统计技术;（2）精通高级多模式神经成像 分析方法，如awFC、BSMac，以及SVC在高维数据中的应用;（3）设计并执行一个 纵向成像研究;实施先进的纵向统计分析技术;（4）接收 神经心理学测试的管理和分析培训;（5）了解神经心理学的理论和现状 衰老的神经生物学知识;（6）了解医学并发症之间的相互关系， 健康和心理社会因素与神经和认知变量;（7）接触多梯度T2 松弛法和动物研究实践;和（8）接受广泛的培训，在负责任的行为 research.这些目标将在指导委员会的支持下实现，指导委员会由Dr. 我的主要导师是DuBois Bowman，共同导师是Yaakov Stern博士， 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，应用先进的技术对收集到的 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补助金。 研究表明，在一些认知能力上的表现，如推理能力， 老年人然而，事实知识，如词汇，仍然相对完整，实际上 随着年龄增长。如果衰老是一种全脑现象，人们会认为认知能力会随着年龄的增长而恶化。 衰老词汇和其他结晶知识的保存是令人惊讶的， 通常与衰老有关的神经衰退。理解这种分歧现象是如何 由单一神经系统支持的一个系统提供了令人兴奋的翻译潜力。检查结构/轴突 两个认知领域之间的功能差异与不同的成熟过程可能 揭示衰老衰退与衰老维持的不同机制。在下面的建议中，博士。 Gazes将采用横断面和纵向研究设计来检验假设，即功能性 大脑区域的网络以及与词汇相关的灰质和白色物质的完整性 随着年龄的增长而维持，而功能性和灰质和白色物质网络则发生实质性下降 与推理有关。在横断面上，她将使用来自6个国家375名参与者的fMRI和DTI。 几十年来，比较与年龄相关的神经系统的差异，这些神经系统是推理和词汇的基础。 能力.为了了解这些领域的神经系统如何随着年龄的增长而变化， 她将对375名参与者中的90名进行为期4年的随访研究，收集fMRI，DTI， 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)确定是否神经系统（灰色和白色物质和功能连接）的基础 推理能力比词汇能力的神经系统下降得更快，（2） 对预测认知能力的因素（神经、健康和心理社会）进行全面检查 推理和词汇的变化。这项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进行， 神经科认知神经科学部。所有的委员会成员都在校园里 并定期提供。Gazes博士可以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，沿着与专用于她的研究的私人办公空间。的 大学为职业发展提供了大量的资源，包括赠款写作讲习班， 职业发展和晋升。 通过拟议的纵向数据收集和分析，职业发展培训将提供 博士具有独立性所必需的一套全面的研究技能，包括研究设计和 管理，先进的神经成像分析技术，用于更强大的大脑行为建模 关系，以及神经图像处理的更深入的知识，特别强调DTI数据。 有了这个职业发展奖提供的受保护的时间，我将能够成功过渡 成为一名独立的衰老认知神经科学研究者。

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.