Neural Correlates of Discrimination and Generalization in Recognition Memory

描述(由申请者提供)：候选人和职业目标：该项目将支持候选人作为长期记忆认知神经科学的独立研究员的基本培训和发展，特别关注与年龄相关的记忆下降如何与大脑功能变化相关。与痴呆症患者相关的神经心理评估和神经病理学原理的培训将为候选人为拟议的研究活动做准备。候选人的目标之一是学习如何以一种新的方法整合多种方法来进行长期记忆研究。来自多种方法的结果汇聚在对大脑功能网络如何支持记忆提取的更完整的理解上。三名具有不同专长领域的导师将就拟议活动的不同方面向候选人提供建议，包括神经心理评估、高级神经成像分析技术的基本培训，以及将实验工作转化为临床人群的诊断工具。这位候选人通过考察长期记忆提取的有影响力的原创性研究，建立了生产力的记录。拟议中的行为神经科学研究及其转化为轻度认知障碍(MCI)患者的诊断工具，将提供 关于神经网络如何支持识别记忆的新的和重要的见解。环境：加州大学旧金山分校独特的资源和科学社区使该大学成为一个理想的环境，帮助候选人发展成为一名成功的、有创造力的独立研究员。这些机构资源将为候选人提供每天与来自不同学科的杰出实验和临床研究人员互动的机会。新的神经科学大楼将候选人高级培训所需的许多关键资源集中在一个屋檐下(即共同导师、最先进的神经成像设备和记忆与衰老中心)。加州大学旧金山分校临床和翻译科学研究所的课程和服务可供候选人加速他的目标，使基础记忆研究的结果对遗忘型MCI和不同表现型痴呆症患者的临床诊断更有用。研究活动：将使用一种新的心理测量学范式来获得在外显识别记忆测试中表现的客观测量。结果将使用神经计算过程模型(即模式完成和分离)进行解释，该模型是识别记忆中概括和区分的基础。一组年轻人和老年人将在MRI扫描仪中完成记忆测试，同时收集他们的功能神经数据。对行为和功能磁共振结果之间的关联进行的组内分析将阐明支持识别记忆的功能神经网络--特别是高保真记忆。组间比较将揭示与年龄相关的记忆性能下降相关的功能网络的变化。神经成像研究中使用的行为范式将转化为客观评估痴呆症患者识别记忆的临床工具。最后，对年轻人的额外实验将使用重复的TMS来测试皮层感兴趣区域在功能记忆网络中的因果作用。

DESCRIPTION (provided by applicant): Candidate and career goals: The project will support the candidate's essential training and development as an independent investigator of the cognitive neuroscience of long-term memory with a particular focus on how age-related decline in memory is associated with changes in brain function. Training in the principles of neuropsychological assessment and neuropathology related to patients with dementia will fill out the candidate's preparation for the proposed research activities. One of the candidate's goals is to learn how to integrate multiple methodologies in a new approach to long-term memory research. Results from multiple methodologies converge on a more complete understanding of how functional brain networks support memory retrieval. Three mentors with distinct areas of expertise will advise the candidate on different aspects of the proposed activities, including essential training in neuropsychological assessment, advanced neuroimaging analysis techniques and translation of experimental work into diagnostic tools for clinical populations. The candidate has established a record of productivity with impactful, original research that examines long-term memory retrieval. The proposed research in behavioral neuroscience, and its translation to diagnostic tools for patients with Mild Cognitive Impairment (MCI), will provide new and important insights about how neural networks support recognition memory. Environment: The exceptional resources and scientific community at UCSF make the university an ideal environment to foster the candidate's development into a successful and creative independent investigator. These institutional resources will give the candidate daily opportunities for interaction with distinguished experimental and clinical researchers from various disciplines. The new Neurosciences Building brings together under one roof many of the key resources needed for the candidate's advanced training (i.e., co- mentors, state-of-the-art neuroimaging equipment and the Memory & Aging Center). Courses and services from the UCSF Clinical and Translational Science Institute are available to the candidate to accelerate his aims to make results from basic memory research more useful for clinical diagnosis of patients with amnestic MCI and different phenotypes of dementia. Research activity: A new psychometric paradigm will be used to acquire objective measures of performance on tests of explicit recognition memory. Results will be interpreted using a neural-computational model of processes (i.e., pattern completion and separation) that underlie generalization and discrimination in recognition memory. Groups of younger and older adults will complete memory tests in the MRI scanner while their functional neural data are collected. Within-group analyses of associations between behavioral and fMRI results will elucidate the functional neural networks that support recognition memory- in particular, high fidelity memory. Between-group comparisons will reveal alterations in the functional networks associated with age- related decline in memory performance. The behavioral paradigm used in the neuroimaging studies will be translated to a clinical tool useful in objective assessment of dementia patients' recognition memory. Finally, additional experiments with younger adults will use repetitive TMS to test the causal role of cortical regions of interest in the functional memory networks.