High-Resolution Structural and Functional Brain Imaging of Medial Temporal Lobe i

描述（由申请人提供）：我们的记忆随着年龄的增长而变化。阿尔茨海默病相关的记忆力下降本身代表了一个重大的公共卫生影响，但认知能力下降-特别是记忆力下降-已被证明是阿尔茨海默病（AD）的一个重要风险因素。检查神经认知老化将帮助我们更好地表征整个生命周期中大脑的病理和非病理变化，并确定认知衰退的临床前标志物。 该项目将我们先前的工作扩展到与年龄相关的记忆衰退的确切性质及其神经基础。像我们之前的项目一样，这个提议大量借鉴了衰老的动物模型和记忆的计算模型来测试与年龄相关的记忆衰退的特定假设。在我们之前的资助期间，我们几乎完全专注于海马体，展示了海马体回路中与年龄相关的中断，与啮齿动物中发现的中断平行，并展示了这些变化如何影响特定类型的记忆。特别是，我们展示了人类海马齿状回是如何凭借其特殊的模式分离能力，或将相似的记忆彼此隔离的能力，在情节记忆中发挥重要作用的。我们还展示了这个回路是如何在衰老过程中逐渐被破坏的，以及这是如何与年龄相关的记忆细节或情节成分的丧失有关的。 这个项目的一个目标是广泛地建立在行为任务的基础上，这些任务是我们开创的，并且在这个领域被广泛采用，这样我们就可以开发和神经生物学验证一整套行为任务，这些任务对海马体功能和与年龄相关的认知衰退最敏感。由于这种损失并不局限于海马，但包括在相邻的内侧颞叶皮层和前额叶皮层的变化，我们建议详细检查这些地区的变化，并在他们与海马的相互作用。在这里，我们再次大量借鉴啮齿动物的神经生物学研究结果，以测试特定的假设，年龄相关的变化，如嗅周皮层的区域，并评估海马和前额叶年龄相关的变化在记忆中的功能贡献和相互关系的变化。 像我们以前的工作一样，我们建议从大样本的成年人中收集一套全面的行为和神经影像学数据。通过收集每个参与者的一套广泛的措施，我们可以检查相互关系，否则是不可能的。除了我们自己的具体问题和假设，广泛的措施（其中包括纵向评估参与者从我们以前的工作）将是有价值的其他研究人员。与以往一样，我们将向其他各方广泛提供数据的所有组成部分。

DESCRIPTION (provided by applicant): Our memory changes as we age. Age-related memory decline in and of itself represents a significant public health impact, but cognitive decline - and in particular memory decline - has been shown to be an important risk factor for Alzheimer's Disease (AD). Examining neurocognitive aging will help us better characterize pathological and non-pathological changes in the brain throughout the lifespan and identify preclinical markers for cognitive decline. This project extends our prior work into the exact nature of age-related memory decline and into its neural bases. Like our prior project, this proposal draws heavily on animal models of aging and computational models of memory to test specific hypotheses about age-related memory decline. In our prior funding period, we focused almost exclusively on the hippocampus, demonstrating age- related disruptions in the hippocampal circuit that parallel those found in the rodent and demonstrating how these changes affect specific kinds of memory. In particular, we showed how the human hippocampal dentate gyrus is critically involved in episodic memory by virtue of its exceptional capacity for performing pattern separation, or the ability to isolate similar memories from each other. We also showed how this circuit is disrupted gradually over the course of aging and how this is linked to age-related loss of the detail or episodic components of a memory. One goal of the project is to build extensively on the behavioral tasks that we have pioneered and that are being widely adopted in the field so that we can develop and neurobiologically validate an entire suite of behavioral tasks that are maximally sensitive to hippocampal function and to age- related cognitive decline. As this loss is not confined to the hippocampus, but includes changes in the adjacent medial temporal lobe cortices and in the prefrontal cortex, we propose to examine in detail changes in these regions and in their interactions with the hippocampus. Here again we draw heavily on neurobiological findings from the rodent to test specific hypotheses about age-related changes in regions like the perirhinal cortex and to assess changes in the functional contributions of and interrelationship between hippocampal and prefrontal age-related changes in memory. Like our prior work, we propose to collect a comprehensive suite of behavioral and neuroimaging data from a large sample of adults. By collecting an extensive set of measures on each participant, we can examine interrelationships that would otherwise be impossible. In addition to our own specific questions and hypotheses, the extensive set of measures (which includes longitudinal assessment of participants from our prior work) will be valuable to other researchers. As before, we will make all components of the data widely available to others.