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进行以患者为导向的研究的必要技能，并在生物统计学，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行为方面进行具体的教学培训。该项目的总体目标是确定注意力和记忆系统的功能性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脑区。目前还不清楚为什么一些MCI患者进展为痴呆症，表现出特定认知脑区的选择性脆弱性，而另一些患者则保持稳定甚至改善。大脑激活的改变已经专门使用情景记忆任务进行了评估。这种方法在范围上仍然有限，因为许多MCI患者在注意力/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，我们的提案将重点关注注意力和记忆的功能性MRI范式，其中受试者必须首先在预期期间保持注意力集中（注意力），然后编码和识别视觉呈现的刺激（记忆）。我们将研究MCI患者和健康对照组中选择脑区的差异性、任务特异性激活。此外，将注意力和记忆阶段的神经反应与脑萎缩和认知表现进行比较。目的1的目标是表征在注意和记忆范式中神经活动的改变，并评估MCI患者的功能和结构MRI之间的关系。目标2的目标是测量传统的注意力和记忆力神经心理学测试与功能性大脑激活之间的关联。本研究的长期目标是在MCI和健康对照组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，我们将收集多个时间点的功能磁共振成像和认知数据，并研究认知下降，改善或保持稳定时潜在BOLD信号的变化。这将提高我们对BOLD信号和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（参见说明）：虽然在了解AD和其他痴呆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能力下降的MCI患者是一个关键的公共卫生问题，但尚未确定有效的生物标志物。功能磁共振成像是一种有前途的新方法，在体内研究早期神经变化的认知能力下降或风险。

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.