Neural Mechanisms Underlying Nicotine and Alcohol Combinations: Quantitative fMRI

尼古丁和酒精组合背后的神经机制：定量功能磁共振成像

• 批准号: 8423709
• 负责人: LISA D NICKERSON
• 金额: $ 18.04万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2014-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8423709
• 关键词: Acute; Alcohol consumption; Alcoholism; Alcohols; Area; Biological; Blood Volume; Blood flow; Brain; Brain imaging; Caffeine; Cessation of life; Complex; Core-Binding Factor; Data; Development; Diffusion; Disease; Drug Combinations; Drug usage; Functional Magnetic Resonance Imaging; Future; Goals; Health; Hour; Image; Imaging Techniques; Intake; Light; Link; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Methods; Modality; Motor; Nature; Neurons; Neurophysiology - biologic function; Nicotine; Oxygen; Participant; Pattern; Perfusion; Persons; Pharmaceutical Preparations; Physiological; Physiological Effects of Drugs; Placebos; Psychotropic Drugs; Randomized; Research; Research Design; Research Methodology; Rest; Rewards; Scanning; Smoke; Smoker; Smoking; Spin Labels; Study Subject; Task Performances; Techniques; Testing; Time; Visual; alcohol effect; alcohol testing; base; blood oxygenation level dependent response; cerebrovascular; cognitive function; drinking; drug of abuse; drugged driving; imaging modality; independent component analysis; innovation; insight; mesolimbic system; neuromechanism; nicotine patch; non-smoker; novel; novel strategies; problem drinker; relating to nervous system; research study; response; volunteer

Long-term Objectives: Our long-term objective is to bring together non-invasive quantitative functional magnetic resonance imaging (q-fMRI) with a newly developed cutting-edge analysis method to study changes in neuronal metabolism and cerebrovascular function that occurs during psychoactive drug use. Specific Aims: Our first specific aim is to validate the components of the q-fMRI acquisition, which requires several different kinds of fMRI scans (or multimodal measurements). The second aim then applies the q-MRI method to study the functional brain networks that define brain activity when a person is simply resting and not engaged in any activity. These networks each consist of a unique set of regions that spontaneously fluctuate together in order to be "tuned" for future task performance. The effects of nicotine and alcohol and their interaction on these resting state networks are the focus of the application of our new q-fMRI strategy. q-fMRI measurements require several different scans, including making measurements of perfusion and oxygen metabolism, and an integrated analysis of all of these different results will be much more informative than separate analyses of each measurement. However, the analysis method, the linked independent component analysis (linked ICA) approach is very new and has never been applied to q-fMRI measurements or any other measurements of psychoactive drug effects. Thus, the third aim is to apply this novel analysis method to data acquired under different drug conditions to identify patterns of related activity in our multimodal fMRI data. Research Design and Methods: A randomized within-subject study of 23 healthy subjects will be done as follows: fMRI scanning will begin four hours after pre-treatment with either nicotine or placebo patch (randomized). Alcohol will then be consumed by subjects while in the scanner and a second scanning session will be done of the combination of nicotine (placebo) + alcohol to assess changes in resting state functional connectivity due to alcohol and nicotine and their interactions. Significance: Linked ICA with q-fMRI measurements is an innovative strategy for studying brain function that could have a significant impact in the ability of fMRI to give an integrated picture of the spectrum of effects that drugs of abuse may have on brain function, and is thus ideally suited to the goals of the CEBRA mechanism. By applying this technique to study alcohol and nicotine co-use, we also will contribute greatly to the understanding of this significant health problem.

长期目标：我们的长期目标是将非侵入性定量功能结合在一起 磁共振成像（q-fMRI）采用新开发的尖端分析方法来研究变化 使用精神活性药物期间发生的神经元代谢和脑血管功能。 具体目标：我们的第一个具体目标是验证 q-fMRI 采集的组成部分，这需要 几种不同类型的功能磁共振成像扫描（或多模态测量）。第二个目标是应用 q-MRI 研究定义一个人只是休息而不是休息时大脑活动的功能性大脑网络的方法 从事任何活动。这些网络各自由一组独特的区域组成，这些区域会自发波动 一起以便针对未来的任务性能进行“调整”。尼古丁和酒精的影响及其 这些静息态网络上的相互作用是我们新的 q-fMRI 策略应用的重点。功能磁共振成像 测量需要多次不同的扫描，包括测量灌注和氧气 新陈代谢，对所有这些不同结果的综合分析将比 对每个测量进行单独分析。然而，分析方法，链接的独立成分 分析（链接 ICA）方法是非常新的，从未应用于 q-fMRI 测量或任何其他 精神活性药物作用的测量。因此，第三个目标是将这种新颖的分析方法应用于数据 在不同药物条件下采集，以确定我们的多模态功能磁共振成像数据中的相关活动模式。 研究设计和方法：将对 23 名健康受试者进行随机受试者内研究，如下 如下：功能磁共振成像扫描将在使用尼古丁或安慰剂贴片进行预处理后四小时开始 （随机）。然后，受试者在扫描仪中和第二次扫描过程中会饮用酒精 将尼古丁（安慰剂）+酒精的组合进行，以评估静息状态功能的变化 由于酒精和尼古丁及其相互作用而产生的连通性。 意义：将 ICA 与 q-fMRI 测量相结合是研究大脑功能的创新策略 可能会对功能磁共振成像的能力产生重大影响，从而提供影响范围的综合图像 滥用药物可能会影响大脑功能，因此非常适合 CEBRA 机制的目标。 通过应用这项技术来研究酒精和尼古丁的共同使用，我们也将为 了解这一重大健康问题。