Functional MRI Investigations of Attention and Memory Systems in MCI

MCI 中注意力和记忆系统的功能 MRI 研究

• 批准号: 7707532
• 负责人: Judy Pa
• 金额: $ 12.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707532
• 关键词: Address; Age; Age-Years; Alzheimer' s Disease; Alzheimer' s disease risk; Attention; Behavioral; Biological Markers; Biological Neural Networks; Biometry; Brain; Brain region; Clinical; Clinical Markers; Clinical Research; Cognition; Cognitive; Cues; Data; Data Analyses; Dementia; Detection; Development; Diagnosis; Ear; Early Diagnosis; Episodic memory; Ethics; Evaluation; Exhibits; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Impaired cognition; Individual; Instruction; Investigation; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Memory; Memory impairment; Methods; Neuroanatomy; Neurology; Neuropsychological Tests; Participant; Patients; Performance; Phase; Predictive Value; Prefrontal Cortex; Public Health; Recruitment Activity; Research; Research Personnel; Risk; Scanning; Sensitivity and Specificity; Signal Transduction; Staging; Stimulus; System; Temporal Lobe; Testing; Thick; Time; Training; Validation; blood oxygenation level dependent response; brain tissue; brain volume; career development; cerebral atrophy; design; executive function; follow-up; gray matter; improved; in vivo; interest; memory encoding; neuropathology; neuropsychological; novel; patient oriented research; programs; relating to nervous system; research study; response; skills; tool

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.

描述(由申请人提供)：本提案的目的是支持候选人发展成为一名独立的临床研究人员。概述的培训计划将使申请者具备必要的技能，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指导方面的具体教学培训，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大脑功能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。目前尚不清楚为什么一些MCI患者进展为痴呆症，表现出认知特定脑区的选择性脆弱性，而另一些患者保持稳定甚至改善。大脑激活的变化仅通过情景记忆任务进行评估。这种方法的范围仍然有限，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，我们的建议将重点放在注意力和记忆的功能磁共振范式上，在这种范式中，受试者必须首先在预期期内保持专注(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特定脑区的不同任务特异性激活。此外，注意力和记忆阶段的神经反应将与大脑萎缩和认知表现进行比较。目标1的目标是描述注意和记忆范例期间神经活动的变化，并评估MCI患者的功能磁共振和结构磁共振之间的关系。目标2的目标是衡量注意力和记忆的传统神经心理学测试与大脑功能激活之间的联系。这项研究的长期目标是在一项关于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fMRI和认知数据，并研究随着认知的下降、改善或保持稳定，潜在的大胆信号的变化。这将提高我们对大胆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衰退患者或有认知衰退风险的人的生物标记物的效用。相关性(见说明)：尽管在理解阿尔茨海默病和其他痴呆方面取得了很大进展，但仍然没有有效的方法来进行早期诊断。识别可能遭受进一步认知衰退的MCI患者是一个关键的公共卫生问题，但目前还没有有效的生物标志物被识别出来。功能磁共振成像是一种很有前景的新方法，可以在体内研究有认知功能减退或有认知功能减退风险的人的早期神经变化。