What is the relationship between BOLD fMRI and functional MRS in aging and MCI?

项目摘要 我们的记忆力随着年龄的增长而变化。与年龄相关的记忆力下降本身就代表了一个重要的公众 对健康的影响，但认知能力下降--尤其是记忆力下降--已被证明是一个重要的 阿尔茨海默病(AD)的危险因素。检查神经认知老化将有助于我们更好地描述 整个生命周期中大脑的病理和非病理变化，并确定临床前标志物 治疗认知功能减退。 这项提议的目标是开发和比较一种新的脑成像方法--功能磁学 磁共振成像光谱学(FMRS)与更传统的BOLD功能磁共振 健康老龄化和轻度认知障碍(MCI)的磁共振成像技术。已经使用了大胆的功能磁共振成像 广泛研究与衰老和MCI相关的神经活动的差异，但它有局限性，可能 对于我们对这些数据的解释至关重要。特别是，神经-血管系统偶联比率(M)在 老龄化，这样与年龄相关的大胆措施的变化可能不是由于年龄相关的潜在变化 神经活动，但在血管系统中。在这里，我们在FMR中提出了一种完全不同的方法，它具有 提供一种可能与神经活动更直接联系的测量方法的额外优势可能比 我们与血液流动之间的联系。 我们将开发一种新的FMRS技术，它将在参与者参与各种不同的活动时收集代谢物数据 认知任务。FMRS信号将更直接地测量细胞活动、能量和 衰老大脑中的细胞结构和丢失。特别是，激励和抑制将是动态的 在记忆任务中通过同时定量谷氨酸、谷氨酰胺和GABA来测量 在同一位置测量黑体功能磁共振成像。总而言之，这些测量将使我们能够检查 BOLD功能磁共振成像和代谢的关系，以及这些如何随着年龄和早期痴呆的变化而改变。它 还将使我们有机会测试以下几个任务中的任何一个是否可以用作 大胆的fMRI任务，以及帮助我们更直接地将人类数据和记忆力下降与 啮齿动物的神经生物学模型。他们还将让我们有机会探索生物标记物/ 行为关系，并进一步了解与衰老相关的细胞结构变化。

Project Summary 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. The goal of this proposal is to develop and compare a novel method of brain imaging, functional magnetic resonance imaging spectroscopy (fMRS) with the more traditional BOLD functional magnetic resonance imaging (MRI) techniques in healthy aging and mild cognitive impairment (MCI). BOLD fMRI has been used extensively to study differences in neural activity associated with aging and MCI, but it has limitations that may be critical to our interpretation of these data. In particular, the neuro-vasculature coupling ratio (M) is altered in aging, such that age-related changes in BOLD measures may not be due to age-related changes in underlying neural activity, but in vasculature instead. Here, we propose an altogether different approach in fMRS that has the added advantage of providing a measure that may be might be more directly linked to neural activity than the link we have with blood flow. We will develop a novel fMRS technique that will collect metabolite data while participants engage in various cognitive tasks. The fMRS signal will more directly measure cellular activity, energetics, and markers of cellular structure and loss in the aging brain. In particular, excitation and inhibition will be dynamically measured during a memory task by quantifying glutamate, glutamine and GABA while simultaneously measuring BOLD fMRI at the same location. Together, these measurements will allow us to examine the relationship between BOLD fMRI and metabolics and how these are altered with aging and early dementia. It will also give us the opportunity to test whether any of several tasks can serve as an age-invariant baseline in BOLD fMRI tasks as well as to help us more directly link human data and memory decline to the neurobiological models from the rodent. They will also give us the opportunity to explore biomarker / behavioral relationships and to further our understanding of changes in cellular structure related to aging.