Neural Correlates of Discrimination and Generalization in Recognition Memory

描述（由申请人提供）：候选人和职业目标：该项目将支持候选人的基本培训和发展，作为长期记忆的认知神经科学的独立研究者，特别关注与年龄相关的记忆力下降与大脑功能变化的关系。与痴呆患者相关的神经心理学评估和神经病理学原则的培训将填写候选人对拟议研究活动的准备。候选人的目标之一是学习如何在长期记忆研究的新方法中整合多种方法。来自多种方法的结果汇聚在对功能性大脑网络如何支持记忆检索的更完整的理解上。三名具有不同专业领域的导师将就拟议活动的不同方面向候选人提供建议，包括神经心理评估的基本培训，先进的神经成像分析技术以及将实验工作转化为临床人群的诊断工具。候选人通过有影响力的原创研究建立了生产力记录，该研究考察了长期记忆检索。这项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重要见解。工作环境：UCSF的特殊资源和科学界使该大学成为一个理想的环境，以促进候选人的发展成为一个成功的和创造性的独立调查员。这些机构资源将使候选人每天有机会与来自不同学科的杰出实验和临床研究人员进行互动。新的神经科学大楼汇集了候选人高级培训所需的许多关键资源（即，共同导师，最先进的神经成像设备和记忆与衰老中心）。来自UCSF临床和转化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和不同痴呆表型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范式来获得外显再认记忆测试的客观表现指标。结果将使用过程的神经计算模型（即，模式完成和分离），这是识别记忆中的概括和区分的基础。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成像结果之间关联的组内分析将阐明支持识别记忆的功能性神经网络，特别是高保真记忆。组间比较将揭示与年龄相关的记忆表现下降相关的功能网络的改变。神经影像学研究中的行为范式将被转化为一种临床工具，用于客观评估痴呆患者的再认记忆。最后，对年轻人的其他实验将使用重复的TMS来测试功能记忆网络中感兴趣的皮层区域的因果作用。

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.