NEURAL NETWORK STABILITY AND VARIABILITY IN NORMAL AGING

这是一个K-23 NIA指导的面向患者的研究职业奖的要求，达伦R Gitelman，医学博士在M-马塞尔梅苏拉姆，医学博士，西北大学神经病学和精神病学教授的指导下。行为老化研究的一个重要目标是调查认知能力的年龄相关变化。然而，并非所有的认知功能都受到衰老过程的影响。随着年龄的增长，代表新概念的获得和对新情况的适应的“流体”认知功能表现出最大的衰退。相比之下，“结晶化”的智力能力反映了对先前学习的信息和技能的使用，并且受年龄的影响最小。这种二分法在许多关于认知老化的研究中得到了支持，但这些缺陷背后的大脑变化在很大程度上仍然难以捉摸。目前的功能解剖脑组织理论表明，许多（如果不是全部的话）高级皮层功能是由大脑区域的互联网络所支持的。目前的建议的目标是使用功能磁共振成像检查神经网络组织中与年龄相关的变化，并评估这些网络组织中的稳定性，当“流体”认知域与“结晶”域进行比较时。通过使用神经网络框架来解释功能成像激活，该项目将超越以往研究中报告的大脑激活的增加或减少。使用较新的统计模型（随机效应和结构方程模型）分析功能成像数据将允许分别通过任务和区域间相互作用改善受试者的评估。Gitelman博士将每年在伦敦与Karl Friston博士一起工作1个月，接受成像统计和功能成像实验设计方面的培训。MRI培训将由Alice Wyrwicz博士监督，还将包括西北大学的托德帕里什博士。Kevin LaBar博士将提供有关认知任务设计的监督。Sandra Weintraub博士将指导Gitelman博士对患者群体进行神经心理学测试。在这个项目中获得的技能和经验应该使Gitelman博士成为认知神经科学的独立研究者，专门从事与功能性神经成像相关的应用。

This is a request for an K-23 NIA Mentored Patient Oriented Research Career Award for Darren R Gitelman, MD under the mentorship of M-Marsel Mesulam, MD, Professor of Neurology and Psychiatry at Northwestern University. An important goal of behavioral aging research has been the investigation of age-related changes in Cognitive abilities. However, not all cognitive functions are equally affected by the aging process. "Fluid" cognitive functions which represent the acquisition of new concepts and adaptation to new situations show the most decline with aging. In contrast, "crystallized" intellectual abilities reflect the usage of previously learned information and skills, and are least affected by aging. This dichotomy has been upheld in numerous studies of cognitive aging, yet the brain changes underlying these deficits have remained largely elusive. Current theories of functional-anatomic brain organization suggest that many, if not all, higher cortical functions are subserved by interconnected networks of brain regions. The goal of the current proposal is to examine age-related alterations in neural network organization using functional magnetic resonance imaging, and to assess the stability in the Organization of these networks when "fluid" cognitive domains are compared to "crystallized" domains. By using a neural network framework to interpret the functional imaging activations this project will look beyond mere increases or decreases in cerebral activations reported in previous studies. Use of newer statistical models (random effects and structural equation modeling) for analyzing the functional imaging data will allow improved assessment of subject by task and interregional interactions respectively. Dr. Gitelman will receive training in imaging statistics and functional imaging experimental design by spending 1 month each year working with Dr. Karl Friston in London. MRI training will be supervised by Dr. Alice Wyrwicz, and will also include Dr. Todd Parrish, both located at Northwestern University. Dr. Kevin LaBar will provide supervision regarding the design of cognitive tasks. Dr. Sandra Weintraub will instruct Dr. Gitelman regarding neuropsychological testing of patient populations. The skills and experience acquired during this project should allow Dr. Gitelman to become an independent investigator in cognitive neuroscience specializing in applications related to functional neuroimaging.