Functional MRI Investigations of Attention and Memory Systems in MCI

该提案的目的是支持候选人发展成为独立的临床研究机构， 研究员概述的培训计划将使申请人具备必要的技能， 在生物统计学，神经解剖学，行为神经学和神经科学方面进行特定的教学培训， 道德和负责任的基础和临床研究行为。本项目的总体目标是确定 注意力和记忆系统的功能性大脑改变是否可以更好地阐明早期脆弱性 MCI患者的大脑区域有认知能力下降的风险。人们仍然不太清楚为什么一些MCI 患者进展为痴呆，表现出特定认知脑区的选择性脆弱性， 有些则保持稳定甚至有所改善。大脑激活的改变已经被专门评估， 情景记忆任务这种方法的范围仍然有限，因为许多MCI患者表现出明显的 注意力/执行功能和记忆领域的缺陷。为了实现这一目标，我们的建议将 专注于注意力和记忆的功能性MRI范例，其中受试者必须首先保持注意力 在预期期间（注意力），然后编码和识别视觉呈现的刺激 （内存）。我们将研究MCI患者选择的脑区的差异性、任务特异性激活 健康的对照。此外，在注意力和记忆阶段的神经反应将是 与脑萎缩和认知能力相比。目标1的目标是描述 在注意力和记忆范式的神经活动，并评估功能和 结构MR！在MCI患者中。目标2的目标是衡量传统 注意力和记忆力以及大脑功能激活的神经心理学测试。远景目标 这项研究的目的是调查在一个特定的年龄段， MCI和健康对照的大规模纵向研究。在未来的研究中，我们将收集多个 功能磁共振成像和认知数据的时间点，并调查作为认知的潜在BOLD信号的变化 下降、改善或保持稳定。这将增进我们对 信号与认知最终，这将使我们能够确定早期神经波动的效用， 认知能力下降或有认知能力下降风险的生物标志物。

The objective of this proposal is to support the candidate's development into an independent clinical researcher. The outlined training plan will equip the applicant with the necessary skills to conduct patientoriented research with specific didactic training in biostatistics, neuroanatomy, behavioral neurology, and the ethical and responsible conduct of basic and clinical research. The overall goal of this project is to determine whether functional brain alterations in attention and memory systems may better elucidate early vulnerable brain regions in MCI patients at risk for cognitive decline. It remains poorly understood why some MCI patients progress to dementia, exhibiting selective vulnerability of cognitive-specific brain regions, while others remain stable or even improve. Alterations in brain activation have been exclusively assessed using episodic memory tasks. This approach remains limited in scope as many MCI patients exhibit pronounced deficits in both attention/executive function and memory domains. To accomplish this goal, our proposal will focus on a functional MRI paradigm of attention and memory in which subjects must first maintain focus during an anticipation period (attention) and then encode and recognize a visually-presented stimulus (memory). We will investigate the differential, task-specific activation of select brain regions in MCI patients and healthy controls. In addition, the neural response during the attention and memory phases will be compared to brain atrophy and cognitive performance. The goal of Aim 1 is to characterize alterations in neural activity during an attention and memory paradigm and assess the relationship between functional and structural MR! in MCI patients. The goal of Aim 2 is to measure the association between traditional neuropsychological tests of attention and memory and functional brain activation. The long-term objectives of this research are to investigate fluctuations in underlying neural networks of attention and memory in a large-scale, longitudinal study of MCI and healthy controls. In future research, we would collect multiple timepoints of fMRI and cognitive data and investigate changes in the underlying BOLD signal as cognition declines, improves, or remains stable. This will improve our understanding of the relationship between the BOLD signal and cognition. Ultimately, this will allow us to determine the utility of early neural fluctuations as a biomarker of those with or at risk for cognitive decline.