认知策略调节尼古丁依赖者心理渴求的神经机制研究

目的:认知策略是一种有效的预防成瘾复吸的方法。因此,研究认知策略对尼古丁依赖者心理渴求的影响及其神经机制可以为探索治疗尼古丁依赖和复吸的心理学和药物干预措施提供理论指导。方法:本课题采用功能性磁共振(fMRI)对认知策略调节尼古丁依赖者心理渴求的神经机制进行研究。扫描范式为部分奖赏条件反射范式,在条件性刺激出现前,给予认知策略进行干预。扫描过程中,同时检测皮肤电导反应(SCR),扫描结束后要求受试者填写心理渴求问卷。结果:(1)行为学结果:戒断后的尼古丁依赖者暴露于伴随香烟的条件性刺激(CS+)时,皮肤电导反应显著增加,同时伴有心理渴求的增加。而认知策略可以非常有效地降低CS+诱发的皮肤电导反应及心理渴求。(2)神经影像学结果:戒断后的尼古丁依赖者暴露于CS+时,激活的脑功能区主要包括:双侧辅助运动区、双侧背外侧前额叶、右侧后扣带、左侧枕上回、左侧顶下小叶、左侧楔前叶、左侧顶上小叶、双侧纹状体尾状核。认知策略调节后,戒断后的尼古丁依赖者暴露于CS+时,激活脑区主要包括:右侧前扣带皮层、左侧旁海马回、右侧楔叶、左侧中央后回,左侧顶上小叶、左侧梭状回、右侧眶额皮层、双侧旁中央小叶、左侧中央前回、右侧额内侧回、右侧背外侧前额皮层。(3)相关性分析发现:认知策略调节心理渴求的下降与认知策略调节右侧前扣带皮层及右侧眶额皮层脑区的激活程度成正相关。结论:尼古丁依赖者对香烟产生期待及心理渴求增加时,与奖赏、记忆、动机相关的脑区激活。认知策略降低尼古丁依赖者对香烟的期待及心理渴求,该调节作用与做决定、情感及认知控制和注意力调节等相关的脑区激活有关。这一发现确定了调节尼古丁依赖者心理渴求的脑区,为治疗尼古丁依赖提供了靶点。

NEURAL SUBSTRATES OF COGNITIVE STRATEGIES REGULATING CIGARETTE CRAVING IN SMOKERS

Background:Craving is a hallmark of drug dependence,including dependence on nicotine. Cognitive regulation has been demonstrated to be effective in treatment of drug abuse by diminishing craving. Although the capacity to cognitive strategy is critical to control craving,its effect on cigarette craving and neural substrates remain unclear. Objectives:In present study,using a cigarette-reward conditioning procedure with cognitive regulation,we examine the effect of cognitive regulation on cigarette craving in abstinent smokers. Methods:We used functional magnetic resonance imaging to ascertain brain regions involved in the cognitive regulation effects. The paradigm includes two conditioned stimuli (CS),either a blue or red square that were either paired (CS+) or not paired (CS-) with a potential unconditioned stimulus (US),a package of cigarettes. Participants were explicitly told the contingencies. Prior to CS presentation,participants were presented with a cue,a single word instruction that told participants to either Attend or Regulate the stimulus. The instruction is presented on a black background for 2 seconds,followed by the CS presentation for 4 seconds and an ISI of 12 seconds,during which time the participant could see a fixation point. The probabilistic US was presented for 500 ms and co-terminated with the CS+. Participants were instructed that they would win a package of cigarettes with each US presentation and accumulate the cigarettes throughout the experiment. Conditions were counterbalanced across participants. There were a total of 72 trials separated into 3 blocks of 20 trials each. Within these blocks,there were 15 trials per type of condition (Attend CS+,Attend CS-,Regulate CS+,and Regulate CS-) and an additional 12 trials where the US were delivered (CS-US trials,6 each for Attend and Regulate conditions). In addition to online condition-based skin conductance response (SCR) and subjective ratings of craving were measured. Results:Inhibition of craving was associated with activation of anterior cingulate cortex (ACC),parahippocampal gyrus,postcentral gyrus,superior parietal lobule,fusiform gyrus,orbitofrontal cortex (OFC). Correlation analysis between decreased craving and regional blood oxygen level dependence (BOLD) signal changes of cognitive regulation responses revealed that the positive correlations in right ACC and the right OFC. Conclusion:Our finding suggests that cognitive regulation can successfully modulate physiological responses,subjective craving and neural substrates underlying the expectation of cigarette in a conditioning procedure. They also indicates that the right ACC,right OFC are components of a neutral circuits implicated in cognitive regulation of cigarette craving.