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: 9179930
• 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/9179930
• 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; Data; Data Analyses; Data Collection; Data Storage and Retrieval; Diffusion Magnetic Resonance Imaging; Educational workshop; Elderly; Environment; Episodic memory; Exhibits; Exposure to; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Grant; Health; Image; 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; 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; Weight; Writing; age group; age related; base; brain health; career; career development; cluster computing; cognitive ability; cognitive change; cognitive neuroscience; cognitive performance; design; follow-up; gaze; gray matter; improved; meetings; 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：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