Neural Mechanisms Underlying Nicotine and Alcohol Combinations: Quantitative fMRI

描述(申请人提供)：我们的长期目标是将非侵入性定量功能磁共振成像(Q-fMRI)与最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采集的组件，这需要几种不同类型的fMRI扫描(或多模式测量)。第二个目的是应用Q-MRI方法研究大脑功能网络，当一个人只是休息而不从事任何活动时，这些网络定义了大脑活动。这些网络中的每一个都由一组独特的区域组成，这些区域自发地一起波动，以便为未来的任务表现进行“调整”。尼古丁和酒精及其相互作用对这些静息状态网络的影响是我们新的Q-fMRI策略应用的重点。Q-fMRI测量需要几种不同的扫描，包括对血流和氧代谢进行测量，对所有这些不同结果的综合分析将比对每种测量的单独分析更具信息量。然而，分析方法，即链接独立分量分析(Linked ICA)方法是非常新的，从未被应用于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在不同药物条件下获得的数据，以识别我们的多模式功能磁共振数据中相关活动的模式。研究设计和方法：对23名健康受试者进行一项随机的受试者内研究，具体如下：功能磁共振成像扫描将在尼古丁或安慰剂贴片(随机)预治疗4小时后开始。然后，受试者在扫描仪中饮用酒精，并进行尼古丁(安慰剂)+酒精组合的第二次扫描，以评估酒精和尼古丁及其相互作用导致的静息状态功能连接性的变化。意义：将ICA与Q-fMRI测量联系起来是研究大脑功能的一种创新策略，可能对fMRI提供滥用药物对大脑功能可能产生的影响的综合图谱的能力产生重大影响，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，我们也将对理解这一重大的健康问题做出重大贡献。 与公共健康相关：我们的长期目标是开发创新的大脑成像技术，以研究精神活性药物使用期间大脑活动的变化。尼古丁和酒精经常一起使用，它们的联合使用每年导致50多万人死亡，死于吸烟相关疾病的酗酒者比死于酒精相关疾病的人更多。我们提出的新方法的第一个应用将是研究尼古丁和酒精对大脑功能的影响，以揭示推动这两种药物联合使用的这两种药物之间的复杂相互作用。

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.