High-resolution multimodal imaging of episodic memory networks in aging.

衰老过程中情景记忆网络的高分辨率多模态成像。

• 批准号: 9352898
• 负责人: Ilana Jacqueline Bennett
• 金额: $ 24.85万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352898
• 关键词: Accounting; Address; Adult; Affect; Aged, 80 and over; Aging; Alzheimer' s Disease; Amyloid; Award; Behavioral; Biological Markers; Biological Neural Networks; Brain; Brain region; California; Clinical; Cognition; Cognitive; Cognitive aging; Complex; Corpus striatum structure; Data; Data Set; Dementia; Diffusion Magnetic Resonance Imaging; Dissociation; Educational workshop; Elderly; Environment; Episodic memory; Event; Foundations; Functional Magnetic Resonance Imaging; Genotype; Goals; Health; Hippocampus (Brain); Human; Impaired cognition; Individual; Institutes; Intervention; Investigation; Knowledge; Learning; Longevity; Magnetic Resonance Imaging; Medial; Mediating; Memory; Memory Loss; Memory impairment; Mentors; Modeling; Motor; Multimodal Imaging; Multivariate Analysis; Neuroanatomy; Neurobiology; Neurocognitive; Pathway interactions; Pattern; Perforant Pathway; Performance; Pharmaceutical Preparations; Phase; Population; Positioning Attribute; Positron-Emission Tomography; Prefrontal Cortex; Process; Research; Research Personnel; Research Proposals; Research Training; Resolution; Resource Development; Retrieval; Risk; Sampling; Scientist; Staging; Structure; System; Techniques; Temporal Lobe; Testing; Training; Universities; Work; age effect; age group; age related; age related cognitive disorder; base; career; career development; healthy aging; in vivo; indexing; interest; memory encoding; mild cognitive impairment; mossy fiber; nervous system disorder; network architecture; neuroimaging; neuromechanism; novel; pathological aging; programs; putamen; relating to nervous system; tenure track; theories; white matter; young adult; Accounting; Address; Adult; Affect; Aged, 80 and over; Aging; Alzheimer' s Disease; Amyloid; Award; Behavioral; Biological Markers; Biological Neural Networks; Brain; Brain region; California; Clinical; Cognition; Cognitive; Cognitive aging; Complex; Corpus striatum structure; Data; Data Set; Dementia; Diffusion Magnetic Resonance Imaging; Dissociation; Educational workshop; Elderly; Environment; Episodic memory; Event; Foundations; Functional Magnetic Resonance Imaging; Genotype; Goals; Health; Hippocampus (Brain); Human; Impaired cognition; Individual; Institutes; Intervention; Investigation; Knowledge; Learning; Longevity; Magnetic Resonance Imaging; Medial; Mediating; Memory; Memory Loss; Memory impairment; Mentors; Modeling; Motor; Multimodal Imaging; Multivariate Analysis; Neuroanatomy; Neurobiology; Neurocognitive; Pathway interactions; Pattern; Perforant Pathway; Performance; Pharmaceutical Preparations; Phase; Population; Positioning Attribute; Positron-Emission Tomography; Prefrontal Cortex; Process; Research; Research Personnel; Research Proposals; Research Training; Resolution; Resource Development; Retrieval; Risk; Sampling; Scientist; Staging; Structure; System; Techniques; Temporal Lobe; Testing; Training; Universities; Work; age effect; age group; age related; age related cognitive disorder; base; career; career development; healthy aging; in vivo; indexing; interest; memory encoding; mild cognitive impairment; mossy fiber; nervous system disorder; network architecture; neuroimaging; neuromechanism; novel; pathological aging; programs; putamen; relating to nervous system; tenure track; theories; white matter; young adult

DESCRIPTION (provided by applicant): The training and research plan proposed in this Pathway to Independence Award will propel the candidate to become an independent scientist in a tenure-track position at a research university. This award will support her investigation of novel questions regarding structural connectivity of neural networks that subserve episodic memory across the lifespan. She will be introduced to high-resolution multimodal neuroimaging and will receive training in corresponding advanced MRI and multivariate analysis techniques. The candidate's expertise in neurocognitive aging research will also be strengthened by the proposal's focus on component processes of episodic memory (i.e., pattern separation), the neural networks that support these processes, and how they are affected in both healthy aging and in individuals at increased risk for dementia. Importantly, this award will prepare the candidate to submit a major research proposal (e.g., R01) at an earlier stage in her career that would be possible otherwise. Environment. The University of California, Irvine (UCI) offers a unique array of training and development resources to facilitate the candidate advancing to an independent scientist position. These include a collaborative group of distinguished researchers at the Center for the Neurobiology of Learning and Memory (CNLM) dedicated to understanding neural mechanisms that support memory, an exceptional mentor (Dr. Craig Stark, Director of the CNLM) and co-mentor (Dr. Claudia Kawas, Clinical Core director of the UCI Institute for Memory Impairments and Neurological Disorders) whose pioneering research programs laid the foundation for the current proposal, access to state-of-the-art research and neuroimaging facilities, and a variety of courses and workshops that will accelerate both educational and career development throughout the duration of this award. Research. The central aim of the current proposal is to investigate neural networks of pattern separation, a component process of episodic memory, across the life span using behavioral and high- resolution multimodal neuroimaging techniques. Episodic memory decline is a hallmark feature of healthy aging and age-related cognitive disorders such as amnestic mild cognitive impairment and Alzheimer's disease. Further detailing the neural mechanisms that support component processes of episodic memory may facilitate identification of neural markers associated with cognitive aging, and inform cognitive and neural interventions aimed at promoting successful aging. Episodic memory is a complex mnemonic ability that involves encoding and retrieval of discrete events, including details such as what, where, and when an event occurred. Successful encoding of new information requires that similar events get separated into distinct memory representations. This process, termed pattern separation, is known to rely on medial temporal lobe (MTL) subregions. However, neuroimaging studies have shown that prefrontal cortex (PFC) and striatum are also engaged during episodic memory performance. Whereas these distributed brain regions are frequently studied in isolation, a comprehensive understanding of the neural substrates of episodic memory in general, and pattern separation in particular, will require knowledge of how they interact as interconnected neural networks. In the mentored phase of this award, high-resolution diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) will be used to identify more accurate models of MTL (Specific Aim 1) and striatal (Specific Aim 2) connectivity across the human lifespan than has been previously acquired in vivo. Expanding on our earlier work with the perforate path, the proposed study will assess the contribution of local tracts connecting MTL subregions (e.g., perforate path, mossy fibers, and schaffer collaterals) and large-scale tracts connecting MTL to PFC (e.g., fornix, cingulum) to pattern separation performance in healthy adults. It will also be the first to examine integrity of tracts connecting striatum to PFC (e.g., caudate-PFC, putamen-motor) in relation to these mnemonic processes. The independent phase of this award will assess interactions and dissociations between MTL and striatal memory systems, which are frequently regarded as being differentially affected by healthy and pathological aging. We will test the hypotheses that degradation of striatal versus MTL tract integrity accounts for pattern separation declines in healthy older versus younger adults (Specific Aim 2) and that degradation of MTL versus striatal tract connectivity accounts for pattern separation declines in oldest- old versus younger-old adults (Specific Aim 3). These data will directly test cortical disconnection theories, which propose that diminished white matter connectivity accounts for cognitive declines associated with aging.

描述（由申请人提供）：在获得独立奖项途径中提出的培训和研究计划将推动候选人成为一所研究大学的终身任职地位的独立科学家。该奖项将支持她对有关神经网络的结构连通性的新问题的调查，这些问题涵盖了整个生命周期的情节记忆。她将被介绍给高分辨率的多模式神经影像学，并将接受相应的高级MRI和多元分析技术的培训。候选人在神经认知衰老研究方面的专业知识也将通过该提案对情节记忆的组成过程（即模式分离），支持这些过程的神经网络以及在健康衰老中如何影响痴呆症风险增加的个体的神经网络。重要的是，该奖项将使候选人在她职业生涯的早期阶段提交一项重大研究建议（例如R01），否则可能是可能的。 环境。加利福尼亚大学尔湾分校（UCI）提供了一系列独特的培训和发展资源，以促进候选人前往独立科学家职位。 These include a collaborative group of distinguished researchers at the Center for the Neurobiology of Learning and Memory (CNLM) dedicated to understanding neural mechanisms that support memory, an exceptional mentor (Dr. Craig Stark, Director of the CNLM) and co-mentor (Dr. Claudia Kawas, Clinical Core director of the UCI Institute for Memory Impairments and Neurological Disorders) whose pioneering research programs laid the foundation for the当前的建议，最先进的研究和神经影像学设施以及各种课程和讲习班，这些课程和讲习班将在整个奖项期间加速教育和职业发展。 研究。当前建议的核心目的是使用行为和高分辨率多模式神经影像技术研究模式分离的神经网络，即情节记忆的一个组成过程。情节记忆下降是健康衰老和与年龄有关的认知障碍（如柔和的轻度认知障碍和阿尔茨海默氏病）的标志性特征。进一步详细介绍支持情节记忆的组成过程的神经机制可能有助于识别与认知衰老相关的神经标记，并为旨在促进成功衰老的认知和神经干预提供信息。情节内存是一种复杂的助记符能力，涉及编码和检索离散事件，包括诸如事件发生的何时，何时和何时诸如详细信息。成功编码新信息要求将类似事件分为不同的内存表示。该过程称为模式分离，已知依赖内侧颞叶（MTL）子区域。但是，神经影像学研究表明，在情节记忆性能中，前额叶皮层（PFC）和纹状体也参与。尽管这些分布式大脑区域经常被孤立地研究，但通常对情节记忆的神经底物进行了全面的了解，尤其是模式分离，将需要了解它们如何作为相互联系的神经网络相互作用。在该奖项的指导阶段，高分辨率扩散张量成像（DTI）和功能性磁共振成像（fMRI）将用于识别MTL（特定AIM 1）和纹状体（特定AIM 2）（特定的AIM 2）（特定的AIM 2）连接性（特定的AIM 2）（特定的AIM 2）在人类寿命中比以前在体内获得的相比。拟议的研究扩展了我们早期的处理过程中的工作，将评估连接MTL子区域（例如，穿孔路径，苔藓纤维和Schaffer侧支）的局部区域以及将MTL连接到PFC（例如，Fornix，Cingulum）对健康成年成年成年成年成年人绩效的大规模区域的贡献。这也将是第一个检查的 将纹状体连接到PFC（例如尾状-PFC，ptamen-Motor）的道路的完整性与这些助记符过程有关。该奖项的独立阶段将评估MTL和纹状体记忆系统之间的相互作用和分离，这些相互作用和纹状体记忆系统经常被视为受健康和病理衰老的差异影响。我们将检验以下假设：纹状体与MTL道的降解是健康老年人与年轻人的模式分离的下降（特定的目标2），并且MTL的降解是MTL的降解，而纹状体道与纹状体的连接性相对于年龄较大的老年人，与年龄较小的成年人相比，模式分离的下降（特定的AIM 3）。这些数据将直接测试皮质断开理论，该理论提出，白质连接性降低的原因是与衰老相关的认知下降。