fMRI Investigations of Cognition in Alcoholics

描述（由申请人提供）：该项目的目的是更好地了解慢性酒精中毒后脑-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的减少或增加，这可能是代偿性的。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，以进一步阐明酒精诱导的神经心理缺陷的本质。我们的工作记忆范式由三个不同的任务阶段组成：信息的编码、维护和检索。到目前为止，尚不清楚在酗酒者中观察到的大脑激活变化是否源于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语言信息（编码）的能力差异，信息排练（维护）的差异，对已保存信息的执行利用（检索）的差异，或者这三者的结合。我们将使用事件相关的功能磁共振成像（fMRI）来检查酒精中毒引起的阶段特异性差异，我们将引入阶段特异性挑战，以进一步检查饮酒和非饮酒受试者之间脑小脑区域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在酒精相关的脑小脑激活变化中的可能分离。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激活增加。我们建议研究这些不同的模式是否反映了不同研究任务的差异，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。这些研究将更好地了解慢性酒精中毒如何改变认知基础的脑功能。

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.