Enhancing Self-Control of Cigarette Craving with Real-Time fMRI

描述（由申请人提供）：吸烟相关疾病每年导致美国超过44万人死亡，全球超过500万人死亡，并且这一数字还在增加。虽然现有的有效疗法使戒烟率增加一倍至三倍，但复发率仍然很高。即使接受了最好的治疗，戒烟的人在一年内仍有高达90%的人复吸。因此，我们迫切需要更好地了解成瘾过程的神经生物学基础，特别是复发，以便开发有针对性的复发预防疗法，帮助人们保持戒断。大多数复发发生在吸烟线索暴露之后。我们最近证明，功能磁共振成像（fMRI）在戒烟前提高线索反应性的措施可以识别吸烟者是否会再次接受尼古丁替代疗法（NRT）；大脑对吸烟相关线索的更大反应与复发有关，并且NRT没有改善。现在有工具可以评估有复吸倾向的吸烟者对吸烟线索的异常大脑皮层和皮层下反应的个体模式，并训练人们调节这种与吸烟线索相关的异常大脑反应，目的是改善与疾病相关的渴望和强迫冲动。这个重新提交的探索性/发展性研究项目将测试这样一个工具，实时功能磁共振成像与情绪调节策略一起使用，作为一种理解和潜在调节成瘾和复发的神经生物学的新方法。这项研究是由博士之间的持续合作。马萨诸塞州总医院（MGH）成瘾医学中心的Evins和Stoeckel在尼古丁依赖的新疗法研究方面有着良好的记录。Gabrieli， Whitfield-Gabrieli和Graybiel是麻省理工学院（MIT）的一个高度创新和多产的认知神经科学家团队，他们开创了这种新颖的成像技术。这项工作有可能提高对复发的大脑机制的理解，并有可能产生一种新的治疗方法，可以减少由慢性、复发性烟草成瘾引起的巨大发病率和死亡率，也有可能提高对相关疾病的理解和治疗，如强迫症，涉及强迫性冲动和抑制控制失败。

DESCRIPTION (provided by applicant): Smoking-related illness causes over 440,000 deaths in the U.S. and over 5 million deaths worldwide annually, and this figure is increasing. Although effective existing therapies double to triple cessation rates, relapse rates remain high. Up to 90 percent of people who quit smoking relapse within the first year, even with the best treatment available. Thus, we face a critical need to develop a better understanding of the neurobiological underpinnings of addictive processes, and of relapse in particular, in order to develop targeted relapse prevention therapies that help people to maintain abstinence. Most relapse occurs following smoking cue exposure. We recently demonstrated that functional magnetic resonance imaging (fMRI) measures of heightened cue-reactivity prior to a smoking cessation attempt identified smokers who would relapse on nicotine replacement therapy (NRT); greater brain reactivity to smoking-related cues was associated with relapse and was not ameliorated by NRT. Tools now exist to evaluate individual patterns of abnormal cortical and subcortical brain reactivity to smoking cues in relapse prone smokers and to train people to modulate this abnormal smoking-related cue-associated brain reactivity with the aim of ameliorating disease-associated craving and compulsive urges. This resubmitted Exploratory / Developmental Research project will test such a tool, real-time fMRI used with emotion regulation strategies, as a novel approach to understanding and potentially modulating the neurobiology of addiction and of relapse in particular. This study is made possible by an ongoing collaboration between Drs. Evins and Stoeckel, at the Massachusetts General Hospital (MGH) Center for Addiction Medicine, who have a track record of study of novel treatments for nicotine dependence, and Drs. Gabrieli, Whitfield-Gabrieli and Graybiel, a highly innovative and productive team of cognitive neuroscientists at the Massachusetts Institute of Technology (MIT), who have pioneered this novel imaging technique. The proposed work has the potential to produce improved understanding of brain mechanisms underlying relapse and potentially, a novel therapy that could reduce the enormous morbidity and mortality caused by chronic, relapsing addiction to smoked tobacco, and also offers the potential for improved understanding and treatment of related disorders such as OCD that involve compulsive urges and failure of inhibitory control. PUBLIC HEALTH RELEVANCE: Addiction to smoked tobacco remains the largest preventable cause of morbidity and premature mortality in the developed world. This study will test neuromodulation with real-time fMRI to determine whether people can gain voluntary control of brain activity associated with craving and whether such control is associated with reduced craving and reduced smoking. If our aims are achieved, we will further our understanding of the neurobiological mechanisms of relapse to nicotine dependence, and we will discover what may become an entirely novel therapy that may improve cessation rates and reduce relapse rates. This technique may also have applications to other addictions, depression, OCD, and ADHD.