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作为长期记忆认知神经科学的独立研究者的基本培训和发展，特别关注与年龄相关的记忆衰退与大脑功能变化之间的关系。在与痴呆症患者相关的神经心理学评估和神经病理学原理方面的培训将为候选人准备拟议的研究活动。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。多种方法的结果汇集在一个更完整的理解如何功能性大脑网络支持记忆检索。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，包括神经心理学评估的基本培训，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。候选人在长期记忆检索方面进行了有影响力的、原创的研究，创造了生产力记录。建议的行为神经科学研究，以及将其转化为轻度认知障碍（MCI）患者的诊断工具，将提供

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.