Spatiotemporal Brain Imaging of Alcohol Effects on Inhibitory Control

描述（由申请人提供）：这是niaaa资助的研究项目资助（R01）的修订申请，题为“酒精对抑制控制的时空脑成像”问题饮酒者通常表现出自我控制和持续目标导向行为的缺陷。这一观察结果与证据一致，表明急性中毒会干扰评估相互冲突的任务需求、抑制冲动反应和执行认知控制的能力。这些损伤可能导致自我约束能力下降，导致饮酒和酒精依赖增加。拟议研究的总体目标是使用多模态脑成像来识别抑制控制的神经回路的时间（“何时”）和空间（“何地”）特征，并确定它们对酒精急性效应的敏感性。将使用功能性磁共振成像（fMRI）来确定酒精引起的诱导变化发生的位置。出色的时间分辨率磁图（MEG）和脑电图（EEG）将阐明这些异常的时间。酒精对“输入”（刺激评估）和“输出”（反应准备、抑制和执行）的影响将同时通过多模态神经成像方法进行研究。据推测，酒精中毒主要破坏了对行为施加自上而下抑制控制的综合前额叶回路。由于战略控制是通过一个复杂的系统施加的，该系统包括这些集成的“输入”和“输出”流的多个阶段，以及错误监测和调节反馈回路，因此多模态成像方法可以揭示潜在神经区域的实时阶段及其对酒精中毒的敏感性。健康受试者作为对照，在酒精和安慰剂条件下分别进行抑制控制和选择性注意实验。此外，在同一个体中获得的性格特征将与神经生理指标一起考虑，并可能揭示酒精对大脑影响的特殊方面和抑制控制的多维性质。这项研究对交通或与工作相关的危害有影响，并可能阐明酒精引起的自我调节功能损伤导致酒精滥用和依赖

DESCRIPTION (provided by applicant): This is a revised application for an NIAAA-sponsored Research Project Grant (R01) entitled "Spatiotemporal Brain Imaging of Alcohol Effects on Inhibitory Control" Problem drinkers often exhibit deficits in self-control and sustained goal-oriented behavior. This observation is consistent with the evidence suggesting that acute intoxication interferes with the ability to evaluate conflicting task demands, inhibit impulsive responses and execute cognitive control. These impairments may result in a decreased ability to exert self restraint, contributing to increased drinking and alcohol dependence. The overall goal of the proposed research is to use multimodal brain imaging to identify the temporal ("when") and spatial ("where") characteristics of the neural circuits subserving inhibitory control and to determine their sensitivity to the acute effects of alcohol. Functional magnetic resonance imaging (fMRI) will be used in order to determine where the alcohol-induced induced changes are occurring. Excellent temporal resolution of magneto- (MEG) and electroencephalography (EEG) will elucidate the timing of these abnormalities. Effects of alcohol on both "input" (stimulus evaluation) and "output" (response preparation, inhibition and execution) will be studied concurrently and with the multimodal neuroimaging approach. It is hypothesized that alcohol intoxication primarily disrupts integrated prefrontal circuitry that exerts inhibitory top-down control on behavior. Since the strategic control is exerted via a complex system involving multiple stages of these integrated "input" and "output" streams in addition to error monitoring and regulatory feedback loops, multimodal imaging approach may reveal the real-time stages of the underlying neural areas and their sensitivity to alcohol intoxication. Healthy subjects will serve as their own controls as they participate in alcohol and placebo conditions in three tasks probing inhibitory control and selective attention. In addition, dispositional traits obtained in the same individuals will be considered together with the neurophysiological indices and may reveal the idiosyncratic aspects of alcohol effects on the brain and the multidimensional nature of inhibitory control. This research has ramifications for traffic- or work-related hazards and may elucidate the alcohol-induced impairment of self-regulatory functions contributing to alcohol abuse and dependence