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

描述（由申请人提供）：在美国，吸烟是导致癌症的主要可预防原因。因此，帮助吸烟者戒烟是减少该国癌症负担的最有效手段之一。由于大多数吸烟者发现戒烟非常困难，因此增强保持戒烟的动机被广泛认为是提高成功机会的重要一步。尝试使用非药物奖励激励戒烟者保持戒烟（例如，钱）是一种特别常见的干预策略。虽然使用非药物奖励来帮助戒烟是基于合理的行为原则，但越来越多的证据表明，非药物奖励在最需要的时候（即，当吸烟者受到吸烟机会的诱惑时）。也就是说，简单地预测在不久的将来会有机会吸烟，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。这种钝化与相应的非药物激励抵制吸烟的意愿下降有关，从而直接破坏了基于奖励的方法促进戒烟的有效性。拟议的研究解决了RFA-CA-13-017（PQA 1）：NCI挑衅性奖励A组（PQA 1）的研究答案，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这种刺激对吸烟者行为影响的有效方法。我们建议使用一种称为实时功能性磁共振成像（fMRI）神经反馈的技术来检查这一想法。实时功能磁共振成像神经反馈是一种生物反馈，它涉及训练个体通过向他们提供有关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）将被随机分配到三组（干预，假神经反馈控制，无反馈控制; n=30）。干预组的人将接受有效的实时功能磁共振成像神经反馈，旨在训练他们自愿增加大脑奖励区域的活动。对照组将经历几乎相同的程序，但分别接受假[安慰剂]神经反馈和无神经反馈。我们假设，只有吸烟者提供有效的神经反馈将学习可靠和自愿增加激活奖励相关的大脑区域使用认知策略（目标1）。我们预测，这种学习将是持久的，这样吸烟者将能够继续使用认知策略，以增加神经反馈被删除后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，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）。如果成功的话，这项研究将为使用神经反馈开辟新的途径，以加快科学发现，并促进有效的吸烟干预措施的发展，这些干预措施可被吸烟者广泛使用。

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.