Regulation of Craving: Stress-challenge and re-exposure effects

压力和渴望是物质使用障碍患者复发的重要预测因素。先前的研究表明，患者可以通过想象在面对物质线索（例如人们吸烟的图像）时使用的长期负面后果来减少自我报告的渴望。在神经方面，这与前额叶皮层的活动有关，结果表明，与烟瘾密切相关的腹侧纹状体和杏仁核等区域的活动减少。第一项研究的目的是检查压力对重度吸烟者调节烟瘾的能力及其神经基质的影响（使用功能性磁共振成像; fMRI）。男性重度吸烟者被随机分配到一个压力诱导（社会评价冷加压任务）或控制条件，并在功能磁共振成像扫描过程中执行一个涉及吸烟和食物（控制）条件的渴望任务。唾液样本将采取在几个时间点，我们假设压力引起的影响，儿茶酚胺和糖皮质激素干扰额前介导的控制机制，从而损害监管的成功（在行为和神经水平）。此外，我们将评估是否执行功能的水平预测保持监管能力，在面对压力。本研究的第二个目的是利用脑电图（EEG）来比较调节渴望及其电生理相关性的策略的预期效果。在这里，晚期正电位（LPP）将作为注意物质线索及其引发渴望的潜力的强大标志。在单个EEG会话期间，重度吸烟者执行渴望任务的调节，该任务涉及通过解决算术问题来想象吸烟和分心的长期负面后果。在短暂的休息后，参与者将重新暴露于先前呈现的物质线索，而没有指示来调节渴望。我们认为，从长远来看，涉及物质线索的策略比仅仅通过分散注意力来减少渴望的策略更成功。吸烟者应该能够通过这两种策略快速降低与吸烟线索相关的渴望和LPP幅度。然而，在再次暴露时，吸烟者应该报告更多的渴望和更高的LPP幅度，以响应先前受到干扰的吸烟线索，相对于先前受到想象吸烟的长期负面后果的吸烟线索，由于调节策略在实验室中经常是成功的，但在真实的生活中实施要困难得多，这个项目将提高我们对促进或损害监管成功的因素以及它们如何相互作用的理解。此外，EEG研究将有助于理解和表征与某些调节策略相关的“反弹效应”及其对渴望和线索暴露的影响。

Stress and craving are important predictors for relapse in patients with substance use disorders. Prior work has shown that patients can reduce self-reported craving by imagining the long-term negative consequences of using when confronted with substance cues (e.g. images of people smoking). Neurally, this was associated with activity of the prefrontal cortex and it was shown that activity of areas such as the ventral striatum and amygdala, which are closely linked with craving, were reduced.The aim of the first study is to examine the influence of stress on the capacity to regulate craving for cigarettes and its neural substrates (using functional magnetic resonance imaging; fMRI) in heavy smokers. Male heavy smokers are randomly assigned to a stress induction (socially evaluated cold pressor task) or control condition and perform a regulation of craving task involving a smoking and food (control) condition during a fMRI scan. Saliva samples will be taken at several time points and we assume that stress-induced effects of catecholamines and glucocorticoids interfere with prefrontally mediated control mechanisms and thus impair regulatory success (at the behavioral and neural level). Further, we will evaluate whether the level of executive functioning predicts maintained regulatory capacity in the face of stress. The aim of the second study of this proposal is to compare the prospective effects of strategies to regulate craving and its electrophysiological correlates using the electroencephalogram (EEG). Here, the late positive potential (LPP) will serve as a robust marker of attention for substance cues and their potential to elicit craving. During a single EEG session, heavy smokers perform a regulation of craving task, which involves imagination of the long-term negative consequences of smoking and distraction through solving arithmetic problems. After a short break, participants will be re-exposed to the previously presented substance cues, without instructions to regulate craving. We assume that strategies involving elaboration of a substance cue are more successful on the long run than strategies to reduce craving by mere distraction. Smokers should be able to rapidly reduce craving and the LPP amplitude associated with smoking cues through both strategies. However, upon re-exposure, smokers should report more craving and higher LPP amplitudes in response to smoking cues previously subject to distraction relative to smoking cues previously subject to imagining the long-term negative consequences of smoking.Since regulation strategies are frequently successful in the laboratory but much more difficult to implement in real life, this project will improve our understanding of factors facilitating or impairing regulatory success and how they interact. Furthermore, the EEG study will facilitate understanding and characterization of “rebound effects” associated with some regulation strategies and their effects on craving and cue-exposure.