NEURAL NETWORK STABILITY AND VARIABILITY IN NORMAL AGING

这是在西北大学神经学和精神病学教授M-Marsel Mesulam的指导下，为医学博士Darren R Gitelman申请K-23 NIA以患者为导向的研究职业奖的请求。行为衰老研究的一个重要目标是研究认知能力与年龄相关的变化。然而，并不是所有的认知功能都同样受到衰老过程的影响。随着年龄的增长，代表获得新概念和适应新情况的“流动”认知功能下降最多。相反，“结晶”的智力反映了以前学到的信息和技能的使用，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。目前的功能解剖学大脑组织理论表明，许多(如果不是全部)更高级的皮质功能被相互连接的大脑区域网络所取代。当前建议的目标是使用功能磁共振成像来检查神经网络组织中与年龄相关的改变，并评估当将“流体”认知域与“结晶”域进行比较时这些网络组织的稳定性。通过使用神经网络框架来解释功能成像激活，该项目将不仅仅着眼于先前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建模)来分析功能成像数据，将分别改进对各任务和区域间相互作用的评估。吉特尔曼博士每年将在伦敦与卡尔·弗里斯顿博士共事1个月，接受成像统计学和功能成像实验设计方面的培训。核磁共振培训将由Alice Wyrwicz博士指导，Todd Parrish博士也将参加，两人都在西北大学。凯文·拉巴尔博士将对认知任务的设计进行监督。桑德拉·温特劳布博士将指导吉特尔曼博士对患者群体进行神经心理测试。在这个项目中获得的技能和经验应该会让吉特尔曼博士成为认知神经科学领域的独立研究员，专门研究与功能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.