Neural recruitment during self-control of smoking: An fMRI paradigm

描述（由申请人提供）：食欲过程（例如，寻求奖励和渴望的某些方面）只是成瘾的一个方面；对药物使用施加“自我控制”的失败尝试是药物依赖的临床诊断。研究自我控制的大脑底物的尝试通常依赖于实验室模型，例如决策任务（例如，爱荷华赌博任务）和抑制控制的速度测试（例如，Go/No-Go任务），这些与戒除吸毒有不确定的相关性。我们建议使用功能磁共振成像（fMRI）结合一种允许在扫描环境中吸入香烟烟雾的专门设备更直接地识别自我控制的基底。50名吸烟者（戒烟12小时）将完成一项“吸烟自控挑战”，该挑战是通过成功的试点工作开发的。这项任务包括两种类型的20秒试验：“不可吸入烟雾”试验，参与者被告知允许吸入香烟的阀门已经关闭；以及“可吸入烟雾”试验，在这种试验中，烟雾立即可用，但参与者被鼓励“尽可能多地不要吸烟”。主要的功能测量将是参与者戒烟的可吸烟试验和不可吸烟试验（“自愿戒烟”-“不可吸烟”）之间fMRI信号的差异。每次试验都会测量渴望（通过按下按钮），以允许其共变，并允许评估其在自愿戒断期间对神经活动的潜在调节作用。功能磁共振成像任务将分两次进行，间隔大约两周。根据初步数据，我们预计自愿禁欲将与右侧腹外侧和背外侧前额叶皮层以及前扣带皮层背侧和辅助运动区神经活动增加有关。标准的心理测量技术将被应用于评估工作表现的可靠性和短期稳定性，以及任务期间功能磁共振成像信号变化。另外两天的行为测试将使任务的表现与既定的决策、抑制控制和个性相关。这种被提议的方法将允许对潜在的自我控制的神经系统进行成像研究，补充现有的用于研究对香烟和药物滥用的渴望的成像方法。随着主要程序的操作和使用，这个为期2年的项目将在基础科学和临床意义上对自我控制的基础产生有价值的见解。

DESCRIPTION (provided by applicant): Appetitive processes (e.g., reward-seeking and some aspects of craving) represent only one side of addiction; failed attempts to exert "self-control" over one's drug use are built-in to the clinical diagnosis of substance dependence. Attempts to study brain substrates of self-control have generally relied on laboratory models, such as decision-making tasks (e.g., the Iowa Gambling Task) and speeded tests of inhibitory control (e.g., the Go/No-Go Task) that have uncertain relevance to abstaining from drug use. We propose to identify substrates of self-control more directly using functional Magnetic Resonance Imaging (fMRI) in conjunction with a specialized apparatus that allows cigarette smoke inhalation in the scanning environment. Fifty cigarette smokers (abstinent 12 h) will complete a "Smoking Self-Control Challenge" that has been developed through successful pilot work. The task includes two types of 20-sec trials: "Smoke Unavailable" trials in which participants are signaled that a valve allowing cigarette smoke inhalation is closed, and "Smoke Available" trials, in which smoke is immediately available, but participants are encouraged to "try not to smoke on as many of these rounds as you can manage". The primary functional measure will be the difference in fMRI signal between Smoke Available trials in which the participant abstains, and trials in which smoke was not available ("Voluntary Abstinence" - "Smoke Unavailable"). Craving will be measured on every trial (by button presses) to allow for its covariation, as well as to allow assessment of its potential moderating effect on neural activity during voluntary abstinence. The fMRI task will be given during two sessions separated by approximately two weeks. Based on preliminary data, we anticipate that voluntary abstinence will be associated with increased neural activity in the right ventrolateral and dorsolateral prefrontal cortex as well as in the dorsal anterior cingulate cortex and supplementary motor area. Standard psychometric techniques will be applied to assess the reliability and short-term stability of performance and of fMRI signal change during the task. Two additional days of behavioral testing will allow performance on the task to be related to established measures of decision-making, inhibitory control, and personality. The proposed method will allow imaging studies of neural systems underlying self-control, complimenting existing imaging methods used to study craving for cigarettes and drugs of abuse. With the primary procedures already operational and in use, this 2-year project should yield valuable insights into the substrates of self-control, with both basic science and clinical implications.