(PQA1) FMRI Neurofeedback and Descision-Making in Habitual Cigarette Smokers

描述(由申请人提供)：在美国，吸烟是可预防癌症的首要原因。因此，帮助吸烟者戒烟是减轻美国癌症负担的最有效手段之一。因为大多数吸烟者发现戒烟非常困难，所以加强戒烟的动力被广泛认为是提高他们成功机会的关键一步。试图通过非药物奖励(例如，金钱)来激励戒烟者保持戒烟是一种特别常见的干预策略。尽管使用非药物奖励来帮助吸烟者戒烟是基于合理的行为原则，但越来越多的证据表明，在最需要非药物奖励的时候(即吸烟者受到吸烟机会的诱惑)，非药物奖励在加强戒烟方面可能是最无效的。也就是说，简单地预计在不久的将来可以吸烟似乎会抑制大脑中支持奖励评估和动机处理的区域对非药物奖励的反应。这种迟钝与出于非药物刺激而抵制吸烟的意愿相应下降有关，因此直接破坏了以奖励为基础的方法促进戒烟的有效性。拟议的研究解决了RFA-CA-13-017(PQA1)：研究回答了NCI的挑衅性问题-A组(PQA1)，通过测试新的假设，即增加大脑对非药物奖励的反应可能是增强此类刺激对吸烟者行为的影响的有效方式。我们建议使用一种名为实时功能磁共振成像(FMRI)神经反馈的技术来检验这一想法。实时功能磁共振神经反馈是一种生物反馈，它包括训练个人通过向他们提供关于正在进行的大脑活动的信息来控制大脑反应。每日吸烟者(n=90)将被随机分成三组(干预组、假神经反馈控制组和无反馈控制组；每组30人)。干预组的人将收到有效的实时fMRI神经反馈，旨在训练他们自愿增加大脑奖励区域的活动。控制组将接受几乎相同的程序，但分别接受假[安慰剂]神经反馈和不接受神经反馈。我们假设，只有获得有效神经反馈的吸烟者才会学习使用认知策略可靠地和自愿地增加与奖励相关的大脑区域的激活(目标1)。我们预测这种学习将是持久的，比如吸烟者在移除神经反馈后将能够继续使用认知策略来增加与奖励相关的大脑活动(目标2)。我们还预测，这种学习将是功能性的，因此当吸烟者在扫描仪外使用相同的策略时，临床相关的决策(选择非药物奖励而不是吸烟的意愿)会受到影响(目标3)。如果成功，这项拟议的研究将开辟新的途径，利用神经反馈来加快科学发现，并促进开发可供吸烟者广泛使用的有效吸烟干预措施。

DESCRIPTION (provided by applicant): Cigarette smoking is the leading preventable cause of cancer in the United States. Helping smokers quit thus is one of the most effective means for reducing cancer burden in this country. Because most smokers find it incredibly difficult to stop smoking, enhancing the motivation to remain abstinent from cigarettes is widely seen as an essential step for improving their chances of success. Attempting to motivate quitting smokers to remain abstinent using nondrug rewards (e.g., money) is a particularly common intervention strategy. Although the use of nondrug rewards to aide quitting smokers is grounded in sound behavioral principles, mounting evidence indicates that nondrug rewards may be the least effective at reinforcing abstinence precisely when they are needed most (i.e., when smokers are tempted by an opportunity to smoke). Namely, simply anticipating having access to cigarettes in the near future appears to dampen the response to nondrug rewards in brain regions supporting reward valuation and motivational processing. This blunting is associated with a corresponding decrease in the willingness to resist smoking for a nondrug incentive, thus directly undermining the effectiveness of reward-based approaches to promoting cigarette abstinence. The proposed research addresses RFA-CA-13-017 (PQA1): Research Answers to NCI's Provocative Questions-Group A (PQA1) by testing the novel hypothesis that increasing brain responses to nondrug rewards may be an effective way to enhance the influence that such stimuli have on behavior in smokers. We propose to examine this idea using a technique called real-time functional magnetic resonance imaging (fMRI) neurofeedback. Real-time fMRI neurofeedback is a type of biofeedback that involves training individuals to control brain responses by presenting them with information about ongoing brain activity. Daily smokers (n=90) will be randomly assigned to three groups (intervention, sham neurofeedback control, and no feedback control; n=30 each). Those in the intervention group will receive valid real-time fMRI neurofeedback aimed at training them to volitionally increase activity in brain reward regions. The control groups will undergo nearly identical procedures but receive sham [placebo] neurofeedback and no neurofeedback, respectively. We hypothesize that only smokers provided with valid neurofeedback will learn to reliably and voluntarily increase activation in reward-related brain regions using cognitive strategies (Aim 1). We predict that this learning will be durable, such tha smokers will be able to continue using cognitive strategies to increase reward-related brain activity after neurofeedback is removed (Aim 2). We also predict that this learning will be functional, such that clinically-relevant decision making (the willingness to choose a nondrug reward over smoking) is influenced when smokers use the same strategies outside of the scanner (Aim 3). If successful, the proposed study will open new avenues for using neurofeedback to expedite scientific discovery and facilitate the development of effective smoking interventions that can be used by smokers on a broad scale.