fMRI Investigations of Cognition in Alcoholics

描述(申请人提供)：本项目的目标是更好地了解慢性酒精中毒后大脑-小脑功能的变化。使用语言和空间工作记忆作为研究认知相关大脑-小脑功能的模型范式，我们的初步研究表明，酒精中毒可以导致激活减少，也可以产生可能是补偿性的增加。我们建议使用事件相关功能磁共振成像(FMRI)方法进一步研究酒精相关的激活变化，旨在更好地揭示酒精诱导的神经心理缺陷的性质。我们的工作记忆范式由三个不同的任务阶段组成，分别是编码、维护和检索信息。到目前为止，还没有确定酗酒者大脑激活的变化是否源于这些任务阶段发生的一个或多个认知需求。具体地说，我们观察到的激活差异可能是由于获取感觉输入和编码言语信息的能力的差异(编码)，信息排练的差异(维护)，维护的信息执行利用的差异(提取)，或者这三者的组合。我们将使用事件相关功能磁共振成像来检查酒精中毒引起的特定阶段的差异，我们将引入特定阶段的挑战，以进一步检查酒精中毒和非酒精中毒受试者之间局部大脑-小脑激活的过程特定变化。我们还将研究语言和空间工作记忆在酒精相关的大脑-小脑激活变化中的可能分离。虽然酒精受试者的空间工作记忆显示额叶激活减少，但文字工作记忆导致左侧额叶和右侧小脑的激活增加。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，或者酒精对语言和空间工作记忆潜在的神经底物的影响的差异。最后，将使用旨在测量血流量、血容量和血氧含量的扫描来确定人群中的大胆信号差异在多大程度上受到血管和/或代谢变化的影响。这些研究将更好地了解慢性酒精中毒是如何改变大脑认知功能的。 与公共健康相关：众所周知，慢性酒精中毒会导致大脑结构的变化，但人们对酒精中毒对潜在认知能力的大脑功能的影响知之甚少。这一方案中的实验旨在利用功能磁共振以及语言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中大脑功能的差异。

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.