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

描述(申请人提供)：与吸烟有关的疾病每年导致美国超过44万人死亡，全球超过500万人死亡，而且这个数字还在增加。尽管现有有效的治疗方法是戒毒率的两倍到三倍，但复发率仍然很高。高达90%的戒烟者在第一年内复发，即使有最好的治疗方法也是如此。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。大多数复发发生在暴露于吸烟线索之后。我们最近证明，功能磁共振成像(FMRI)测量戒烟尝试前线索反应性的增强可以确定吸烟者是否会复发接受尼古丁替代疗法(NRT)；大脑对吸烟相关线索的更高反应性与复发有关，而NRT并不能改善这种情况。现在已经有工具来评估有反复吸烟倾向的人的皮质和皮质下大脑对吸烟线索的异常反应的个体模式，并训练人们调节这种与吸烟相关的异常线索相关的大脑反应，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/发展研究项目将测试这样一种工具，即与情绪调节策略一起使用的实时功能磁共振成像，作为一种新的方法来理解和潜在地调节成瘾，特别是复发的神经生物学。这项研究是麻省总医院(MGH)成瘾医学中心的Evins博士和Stoeckel博士，以及麻省理工学院(MIT)认知神经科学家的高度创新和高产的团队Gabrieli、Whitfield-Gabrieli和Graybiel博士之间的持续合作，他们拥有尼古丁依赖新疗法的研究记录，他们开创了这种新型成像技术。这项拟议的工作有可能提高对复吸背后的大脑机制的理解，并有可能成为一种新的治疗方法，可以降低长期、复发性吸烟成瘾造成的巨大发病率和死亡率，还有可能改善对强迫症等相关疾病的理解和治疗，这些疾病涉及强迫冲动和抑制控制失败。 公共卫生相关性：吸烟成瘾仍然是发达国家发病率和过早死亡的最大可预防原因。这项研究将用实时功能磁共振成像测试神经调节，以确定人们是否可以自愿控制与渴望相关的大脑活动，以及这种控制是否与减少渴望和减少吸烟有关。如果我们的目标得以实现，我们将进一步了解尼古丁依赖复发的神经生物学机制，我们将发现一种可能成为一种全新疗法的方法，它可能会提高戒烟率并降低复发率。这项技术也可能适用于其他上瘾、抑郁症、强迫症和多动症。

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.