Functional MRI Investigations of Attention and Memory Systems in MCI

描述（由申请人提供）：本提案的目的是支持候选人发展成为独立的临床研究人员。概述的培训计划将使申请人具备必要的技能，通过生物统计学，神经解剖学，行为神经学以及基础和临床研究的道德和负责任的具体教学培训进行以患者为导向的研究。该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MCI患者认知能力下降风险的早期脆弱大脑区域。为什么一些轻度认知障碍患者会发展为痴呆症，表现出认知特异性大脑区域的选择性脆弱性，而另一些患者则保持稳定，甚至有所改善，人们对此仍然知之甚少。大脑活动的改变是通过情景记忆任务来评估的。这种方法的应用范围仍然有限，因为许多轻度认知障碍患者在注意/执行功能和记忆领域都表现出明显的缺陷。为了实现这一目标，我们的建议将重点放在注意力和记忆的功能性MRI范式上，在该范式中，受试者必须首先在预期期间保持注意力（注意），然后编码和识别视觉呈现的刺激（记忆）。我们将研究MCI患者和健康对照者的不同的、特定任务的大脑区域激活。此外，注意和记忆阶段的神经反应将与脑萎缩和认知表现进行比较。目的1是表征注意力和记忆范式中神经活动的变化，并评估MCI患者功能和结构MRI之间的关系。Aim 2的目标是测量传统的注意力和记忆神经心理学测试与功能性脑激活之间的联系。本研究的长期目标是在MCI和健康对照的大规模纵向研究中调查潜在的注意力和记忆神经网络的波动。在未来的研究中，我们将收集fMRI和认知数据的多个时间点，研究认知下降、改善或保持稳定时底层BOLD信号的变化。这将提高我们对BOLD信号与认知之间关系的理解。最终，这将使我们能够确定早期神经波动作为认知能力下降或有认知能力下降风险的生物标志物的效用。相关性（见说明）：尽管在了解阿尔茨海默病和其他痴呆症方面取得了很大进展，但仍然没有有效的早期诊断方法。识别可能遭受进一步认知衰退的轻度认知损伤患者是一个关键的公共卫生问题，但尚未发现有效的生物标志物。功能性核磁共振成像是一种很有前途的新方法，可以在体内研究认知能力下降或有认知能力下降风险的患者的早期神经变化。

DESCRIPTION (provided by applicant): 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 patient- oriented 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 MRI 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 time points 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. RELEVANCE (See instructions): Although there are great advances being made on understanding AD and other dementias, there are still no effective methods available for early diagnosis. The identification of MCI patients who are likely to suffer from further cognitive decline is a critical, public health issue, but no effective biomarkers have yet been identified. Functional MRI is a promising new method for in vivo investigation of early neural changes in those with or at risk for cognitive decline.