fMRI Investigations of Cognition in Alcoholics

酗酒者认知功能磁共振成像研究

• 批准号: 8525260
• 负责人: JOHN E DESMOND
• 金额: $ 53.91万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8525260
• 关键词: Alcoholism; Alcohols; Blood; Blood Vessels; Blood Volume; Blood flow; Brain; Cerebellum; Chronic; Cognition; Cognitive; Dissociation; Event; Functional Magnetic Resonance Imaging; Goals; Human; Information Retrieval; Investigation; Laboratories; Left; Light; Maintenance; Measures; Metabolic; Modeling; Nature; Pattern; Performance; Phase; Population; Process; Relative (related person); Research; Retrieval; Scanning; Sensory; Short-Term Memory; Signal Transduction; Staging; Stimulus; System; Time; alcohol effect; cerebral atrophy; chronic alcohol ingestion; cognitive function; design; frontal lobe; hemodynamics; imaging modality; motor control; neocortical; neuroimaging; neuropsychological; non-alcoholic; phonology; problem drinker; public health relevance; rehearsal; relating to nervous system; research study; response; volunteer

DESCRIPTION (provided by applicant): The goal of this project is to better understand the changes in cerebro-cerebellar brain function that occur after chronic alcoholism. Using verbal and spatial working memory as model paradigms for investigating cognitive- related cerebro-cerebellar function, our preliminary investigations have suggested that alcoholism can produce either decreases in activation or increases that may be compensatory in nature. We propose to further investigate alcohol-related changes in activation using event-related functional magnetic resonance imaging (fMRI) methods designed to shed more light on the nature of alcohol-induced neuropsychological deficits. Our working memory paradigm is comprised of 3 distinct task phases of encoding, maintenance, and retrieval of information. It has not been determined whether changes in brain activation observed thus far in alcoholics are derived from one or more of the cognitive demands occurring during these task phases. Specifically, differences in activation we have observed could be due to differences in the ability to acquire sensory input and encode verbal information (encoding), differences in rehearsal of information (maintenance), differences in the executive utilization of the maintained information (retrieval), or a combination of these three. We will use event-related fMRI to examine phase specific differences caused by alcoholism, and we will introduce phase- specific challenges to further examine process-specific changes in regional cerebro-cerebellar activation that differ between alcoholic and non-alcoholic subjects. We will also investigate possible dissociations of verbal and spatial working memory on alcohol-related changes in cerebro-cerebellar activation. Whereas spatial working memory in alcoholic subjects has revealed decreases in frontal lobe activation, verbal working memory has elicited left frontal and right cerebellar increases in activation. We propose to investigate whether these different patterns reflect differences in tasks across studies, differences in alcoholic populations, or differences in the effect of alcohol on neural substrates underlying verbal and spatial working memory. Finally, scans designed to measure blood flow, blood volume, and blood oxygenation will be used to determine to what extent BOLD signal differences in the populations are influenced by vascular and/or metabolic changes. These investigations will provide a better understanding of how chronic alcoholism changes brain function underlying cognition. PUBLIC HEALTH RELEVANCE: Chronic alcoholism is known to cause structural changes in the brain, but little is known about the effects of alcoholism on brain function underlying cognitive performance. The experiments in this proposal are designed to characterize, using functional MRI and tasks of verbal and spatial working memory, differences between alcoholics and non-alcoholics in brain function underlying these fundamental cognitive processes.

描述（由申请人提供）：该项目的目标是更好地了解慢性酗酒后小脑功能的变化。使用言语和空间工作记忆作为研究认知相关脑小脑功能的模型范式，我们的初步研究表明，酗酒可以导致激活减少或增加，这可能是补偿性的。我们建议使用事件相关的功能磁共振成像（fMRI）方法进一步研究与酒精相关的激活变化，旨在更多地了解酒精引起的神经心理缺陷的本质。我们的工作记忆范式由信息编码、维护和检索这三个不同的任务阶段组成。迄今为止，尚未确定在酗酒者中观察到的大脑激活变化是否源自这些任务阶段中发生的一种或多种认知需求。具体来说，我们观察到的激活差异可能是由于获取感官输入和编码言语信息（编码）的能力差异、信息排练（维护）差异、对所维护信息的执行利用（检索）差异或这三者的组合造成的。我们将使用事件相关的功能磁共振成像来检查由酒精中毒引起的阶段特异性差异，并且我们将引入阶段特异性挑战来进一步检查酒精和非酒精受试者之间区域脑小脑激活的过程特异性变化。我们还将研究言语和空间工作记忆与酒精相关的脑小脑激活变化之间可能的分离。酗酒者的空间工作记忆显示额叶激活减少，而言语工作记忆则引起左额叶和右小脑的激活增加。我们建议调查这些不同的模式是否反映了不同研究中任务的差异、酗酒人群的差异，或者酒精对言语和空间工作记忆的神经基质影响的差异。最后，设计用于测量血流量、血容量和血氧的扫描将用于确定人群中 BOLD 信号差异在多大程度上受到血管和/或代谢变化的影响。这些研究将有助于更好地了解慢性酗酒如何改变认知基础上的大脑功能。 公众健康相关性：众所周知，慢性酒精中毒会导致大脑结构变化，但人们对酒精中毒对认知表现背后的大脑功能的影响知之甚少。本提案中的实验旨在利用功能性 MRI 以及言语和空间工作记忆任务来表征酗酒者和非酗酒者在这些基本认知过程背后的大脑功能差异。