Defining individual differences in tobacco smokers using multimodal neuroimaging

 描述（由申请人提供）：尼古丁依赖是一种普遍存在且代价高昂的公共卫生流行病。虽然存在多种治疗选择，但大多数试图戒烟的人 最终会复发。鉴于许多潜在因素可能导致尼古丁依赖，因此不太可能找到一种对所有吸烟者有效的治疗方法。根据个人风险状况指导治疗是提高戒断率的更有效方法，并且符合NIDA“发展导致个性化或定制治疗的知识”的治疗目标。当前提案的主要优势在于，它将通过使用多模式神经影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）直接测量吸烟者的大脑对吸烟线索的反应。这是相关的，因为我们之前的研究表明，即使吸烟者接受尼古丁替代疗法（NRT）的帮助，大脑对吸烟线索的反应性增强也可以预测复吸的可能性。然后，我们将确定当吸烟者借助专门旨在减少提示反应性的治疗（例如不含尼古丁的电子烟）戒烟时，大脑对吸烟提示的高度反应是否可以减弱，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是由于大脑化学物质的破坏（通过磁共振波谱（MRS）测量）和固有的大脑组织（通过功能连接量化）造成的。这些措施将确定用于开发未来治疗的额外分子和神经解剖学目标，并将确定有助于增强提示反应性的潜在神经生物学因素。总的来说，这项研究的结果将对针对特定风险因素的新颖且急需的治疗策略的开发产生重大影响。

 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.