fMRI Investigations of Cognition in Alcoholics

描述（由申请人提供）：本项目的目标是更好地了解慢性酒精中毒后小脑-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的小脑-小脑功能的模型范例，我们的初步研究表明，酒精中毒可以产生激活的减少或增加，这可能是补偿性的。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，旨在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编码、维护和检索信息的3个不同任务阶段组成。迄今为止，在酗酒者中观察到的大脑激活变化是否来自这些任务阶段中发生的一个或多个认知需求，尚未确定。具体来说，我们观察到的激活差异可能是由于获得感官输入和编码语言信息（编码）的能力差异、信息复述（维持）的差异、对维持信息的执行利用（提取）的差异，或者这三种差异的组合。我们将使用事件相关的功能磁共振成像检查由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，以进一步检查酒精和非酒精受试者之间不同的区域小脑-小脑激活的过程特异性变化。我们也将探讨可能的语言和空间工作记忆的分离对酒精相关的变化，小脑-小脑激活。虽然酒精中毒受试者的空间工作记忆显示额叶激活减少，但言语工作记忆引起左额叶和右小脑激活增加。我们建议调查这些不同的模式是否反映了跨研究的任务差异，酗酒人群的差异，或酒精对语言和空间工作记忆相关神经基质的影响差异。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群体中BOLD信号差异受血管和/或代谢变化影响的程度。这些调查将提供一个更好的了解慢性酒精中毒如何改变大脑功能的认知基础。 公共卫生相关性：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大脑功能的影响知之甚少。本提案中的实验旨在使用功能性MRI和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的脑功能中的差异。

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.