Neural Mechanisms Underlying Nicotine and Alcohol Combinations: Quantitative fMRI

长期目标：我们的长期目标是将非侵入性定量功能 磁共振成像（q-fMRI）与新开发的尖端分析方法，以研究变化 神经元代谢和脑血管功能的变化。 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 一种研究功能性大脑网络的方法，当一个人只是休息而不是 从事任何活动。这些网络各自由一组独特的自发波动的区域组成 一起，以便为未来的任务性能进行“调整”。尼古丁和酒精的作用及其 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。q-fMRI 测量需要几种不同的扫描，包括测量灌注和氧气 代谢，对所有这些不同结果的综合分析将比 对每项测量进行单独分析。然而，分析方法，链接独立组件 分析（链接伊卡）的方法是非常新的，从来没有被应用到q-fMRI测量或任何其他 精神活性药物效果的测量。因此，第三个目标是将这种新的分析方法应用于数据 在不同的药物条件下获得，以确定我们的多模态fMRI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：fMRI扫描将在尼古丁或安慰剂贴剂预处理后开始4小时开始 （随机）。然后，受试者将在扫描仪和第二次扫描期间饮用酒精 将对尼古丁（安慰剂）+酒精的组合进行评估，以评估静息状态功能的变化 酒精和尼古丁及其相互作用引起的连接。 意义：伊卡与q-fMRI测量相关联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， 滥用药物可能对大脑功能有影响，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，我们也将大大有助于 了解这一重大健康问题。

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.