Defining individual differences in tobacco smokers using multimodal neuroimaging

 描述(申请人提供)：尼古丁依赖是一种流行且代价高昂的公共卫生流行病。虽然有几种治疗选择，但大多数试图戒烟的人 最终会复发。考虑到许多潜在因素可能导致尼古丁依赖，为所有吸烟者找到单一有效的治疗方法是不太可能的。根据个人风险状况指导治疗是提高禁酒率的更有效方法，符合NIDA的治疗目标，即“发展知识，导致个性化或定制治疗”。当前提议的一个主要优点是，它将通过使用多模式神经成像技术的独特组合来识别吸烟者的差异，从而实现这一目标。首先，我们将使用功能磁共振成像(FMRI)来直接测量吸烟者对吸烟线索的大脑反应。这一点是相关的，因为我们之前的工作表明，即使吸烟者得到尼古丁替代疗法(NRT)的帮助，大脑对吸烟线索的增强反应也预示着复发的脆弱性。然后，我们将确定当吸烟者在专门旨在降低线索反应性的治疗(例如，不含尼古丁的电子烟)的帮助下戒烟时，大脑对吸烟线索的高反应性是否可以被钝化，这可能成为一种可能的个性化治疗选择。我们还将确定线索反应性的差异是否归因于大脑化学的破坏，如磁共振波谱(MRS)所测量的，以及固有的脑组织，如功能连接性所量化的。这些措施将为开发未来的治疗方法确定更多的分子和神经解剖学目标，并将确定导致线索反应性增强的潜在神经生物学因素。总而言之，这项研究的结果将对针对特定风险因素的新的和迫切需要的治疗策略的发展产生重大影响。

 DESCRIPTION (provided by applicant): Nicotine dependence is a prevalent and costly public health epidemic. While several treatment options exist, the majority of individuals who try to quit will eventually relapse. Finding a single efficacious treatment for all smokers is unlikely given that numerous underlying factors can contribute to nicotine dependence. Guiding treatment based on individual risk profiles is a more effective approach to enhance abstinence rates and is in line with NIDA's treatment objective of "developing knowledge that leads to personalized or customized treatments". A major strength of the current proposal is that it will meet this objectiv by identifying differences in smokers using a unique combination of multi-modal neuroimaging techniques. First, we will use functional magnetic resonance imaging (fMRI) to directly measure individual smoker's brain reactivity to smoking cues. This is relevant given our prior work showing that enhanced brain reactivity to smoking cues predicts relapse vulnerability even when smokers are aided by nicotine replacement therapy (NRT). We will then determine whether heightened brain reactivity to smoking cues can be blunted when smokers quit with the aid of treatment specifically aimed at reducing cue-reactivity (e.g., nicotine-free e-cigarettes), which could become a possible personalized treatment option. We also will identify whether differences in cue reactivity are due to disruptions in brain chemistry, as measured by magnetic resonance spectroscopy (MRS) and inherent brain organization, as quantified by functional connectivity. These measures will identify additional molecular and neuroanatomical targets for developing future treatments and will define the underlying neurobiological factors contributing to heightened cue-reactivity. Collectively, the results of this study will have a significant impac on the development of novel and much-needed treatment strategies, which target specific risk factors.