fMRI Correlates of Olfactory and Visual Cues in Tobacco Smoking

描述（由申请人提供）：提示引起的渴望目前在尼古丁依赖中还没有得到很好的理解，并且是一个很差的使用预测。然而，与其他药物滥用一样，研究表明，当使用机会更接近于测量时，渴望测量与药物使用更相关。此外，先前对线索诱导的渴望的研究使用了视觉、听觉和一些触觉线索，这些线索可能会失去显著性。第一颅（嗅觉）神经与中枢神经系统的边缘区域有直接联系，这一事实表明，气味可能在线索诱导的渴望中起着重要作用，因此嗅觉线索可能比其他方式唤起更强烈的反应。这项R21提案的重点是视觉和嗅觉线索对中等吸烟者的影响。使用功能性磁共振成像（fMRI），我们将检查在饱腹和短期禁食期间对这些线索的反应所涉及的大脑回路和活动模式。广义线性模型（GLM）是功能扫描的标准分析方法。然而，GLM方法在设计上忽略了模拟大脑反应的波动，而这种变化本身就是我们感兴趣的。独立成分分析（ICA）提供了一种分析这些数据集的新方法，特别适用于捕捉神经活动中这些复杂的波动。因此，使用ICA来分析结果数据将揭示使用常规分析无法看到的渴望和相关状态的时空大脑模式。我们将进行一项前瞻性线索诱导渴望功能磁共振成像实验，在该实验中，中度吸烟者（15-25支/天）将在饱腹和短期戒烟期间体验视觉和嗅觉吸烟相关线索（与没有吸烟效价的类似刺激相比）。将比较ICA和GLM方法，以便更好地了解嗅觉线索在总体复发，特别是吸烟中所起的作用。我们预计嗅觉线索将产生比视觉线索更大的影响，特别是在先前与渴望相关的区域，并且ICA分析方法将比GLM技术对这些线索诱导的变化更敏感。本探索性研究中发现的最有效的线索和分析方法将用于未来的R01拨款申请，用于检查戒烟后第一个月吸烟者与线索相关的大脑激活。后续研究将检查戒烟辅助、吸烟持续时间和强度、合并症以及性别相关差异对长期戒烟率激活模式预测价值的作用。公共卫生相关性：数百万的美国吸烟者想要戒烟，但由于他们旧病复发而未能实现长期戒烟。更好地了解与烟草有关的线索，特别是气味，如何导致吸烟复发的过程，将有助于开发更有效的治疗策略，可以根据个人情况量身定制。使用新的大脑绘图工具将使这种关系得以确定。

DESCRIPTION (provided by applicant): Cue-induced craving is currently not well understood in nicotine dependence, and is a poor predictor of use. However, as with other drugs of abuse, studies suggest that craving measures become more relevant to drug use when the opportunity to use more closely follows the measurement. Furthermore, previous studies of cue-induced craving have used visual, auditory, and some tactile cues, which may lose salience. The fact that the first cranial (olfactory) nerve has a direct connection to the limbic region of the central nervous system suggests that odors may play a significant role in cue-induced craving and so olfactory cues may evoke a more potent response than other modalities. This R21 proposal focuses on the effects of visual and olfactory cues on medium cigarette smokers. Using functional magnetic resonance imaging (fMRI), we will examine the brain circuitry and activity patterns involved in the responses to these cues during satiety and short-term abstinence. Generalized linear models (GLM) are the standard analysis method for functional scans. However, GLM methods by design ignore fluctuations about the modeled brain response, and this variability is itself of interest. Independent component analysis (ICA) offers a new method to analyze these data sets, particularly suitable for capturing these complex fluctuations in neural activity. Therefore, employing ICA to analyze the resulting data will reveal spatiotemporal brain patterns of craving and related states that are not visible using conventional analyses. We will conduct a prospective cue-induced craving fMRI experiment in which moderate smokers (15-25 cigarettes/day) will experience both visual and olfactory smoking-related cues (contrasted with similar stimuli without smoking valence), during both satiety and short-term abstinence. ICA and GLM methods will be compared in an effort to provide a better understanding of the role that olfactory cues play in relapse in general and to tobacco smoking in particular. We anticipate that olfactory cues will yield a larger effect that visual ones, particularly in regions previously associated with craving, and that ICA analysis methods will be more sensitive to these cue- induced changes than will GLM techniques. The most effective cues and analysis methods found with the present exploratory study will be used in a future R01 grant application examining cue-related brain activation of smokers during the first month after quitting. Follow-up studies will examine the role of quit aids, duration and intensity of smoking, comorbid disorders, and sex-related differences on the predictive value of activation patterns for long-term quit rates. PUBLIC HEALTH RELEVANCE: Millions of American cigarette smokers want to quit, but have not achieved long-term abstinence because they relapse to use. A better understanding of the process of how tobacco-related cues, especially odors, result in relapse to smoking would permit the development of more effective treatment strategies that can be individually tailored. The use of new brain mapping tools will allow such relationships to be identified.