Neural Mechanisms Underlying Nicotine and Alcohol Combinations: Quantitative fMRI

描述（由申请人提供）：我们的长期目标是将无创定量功能磁共振成像（q-fMRI）与新开发的尖端分析方法结合起来，研究精神活性药物使用期间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，这需要几种不同的fMRI扫描（或多模态测量）。第二个目标是应用q-MRI方法来研究大脑功能网络，当一个人只是休息而不从事任何活动时，大脑网络定义了大脑活动。这些网络由一组独特的区域组成，这些区域自发地一起波动，以便“调整”未来的任务性能。尼古丁和酒精对这些静息状态网络的影响及其相互作用是我们新的q-fMRI策略应用的重点。q-fMRI测量需要几次不同的扫描，包括测量灌注和氧代谢，对所有这些不同结果的综合分析将比单独分析每个测量结果提供更多的信息。然而，分析方法，链接独立成分分析（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的分析方法应用于在不同药物条件下获得的数据，以识别我们的多模态fMRI数据中的相关活动模式。研究设计和方法：对23名健康受试者进行随机研究，方法如下：在尼古丁或安慰剂贴片（随机）预处理后4小时开始fMRI扫描。然后，受试者在接受扫描的时候会喝下酒精，然后再进行尼古丁（安慰剂）+酒精的第二次扫描，以评估酒精和尼古丁及其相互作用在静息状态下功能连通性的变化。意义：将ICA与q-fMRI测量相结合是研究脑功能的一种创新策略，它可能对fMRI的能力产生重大影响，从而提供药物滥用可能对脑功能产生的影响的综合图景，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理解这一重大的健康问题。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Our long-term goal is to develop innovative brain imaging techniques to study the changes in brain activity that occur during psychoactive drug use. Nicotine and alcohol are frequently used together and their combined use contributes to more than half a million deaths each year, with more alcoholics dying from smoking-related diseases than from alcohol-related diseases. The first application of the new methods we are proposing will be to study the effects on brain function of nicotine and alcohol together to shed light on th complex interactions between these two drugs that drives their combined use.