Regulation of Craving: Clinical Trial and Neural Mechanisms

摘要/项目摘要 年轻人中大量饮酒(YA)很普遍，并与严重的负面后果有关 包括死亡率和酒精使用障碍风险(AUD)1-7。然而，现有的干预措施已经表明 药效适中8-14，需要创新的干预措施。雅加达干预措施具有广泛的潜力 如果它们是简短的、计算机化的(尤其是基于网络的)并针对核心神经认知，则会产生影响 大量饮酒的潜在机制14，15.两种这样的机制是渴望和对渴望的调节。 在DSM-5中，渴望被定义为“强烈的欲望”16，渴望与饮酒有关，并预测饮酒(例如，17- 25，包括YAS(如26-29)。重要的是，与酒精相关的线索会增加渴望30；这种线索诱导 渴求还与饮酒(例如，31-35岁)相关联，并预测饮酒，包括在YA 32、33、36、37。这些 数据表明，暗示诱导的渴望是饮酒背后的核心机制。始终如一地，技能 渴望的调节训练是许多干预措施的重要特征，包括认知-行为干预 治疗(CBT)45和基于正念的治疗(MBT)46，47。此外，对渴望的调节直接关系到 减少渴求和饮酒，以及更好的治疗结果(例如34，41，42，48-52)，包括53年度。这些 数据表明，渴望的调节是饮酒/戒酒变化的核心机制54。 我们开发了渴求调节(ROC)任务来研究认知、情感和神经机制 与渴求有关，并对55-61号物质进行调节。在一项研究中，饮酒者暴露在 对酒精的想象60。在渴望试验中，他们经历了线索诱导的渴望，并在 区域包括腹侧纹状体和腹内侧额前皮质62-。在监管试验中，他们使用了 以治疗为基础的策略，以调节他们的渴望。我们发现，自我报告的渴望与渴望有关 在规则60期间，神经活动显著减少。然而，通过研究我们发现， 监管运作的神经机制取决于所使用的策略。具体地说，监管 CBT策略(例如，考虑饮酒的负面后果)取决于PFC 56、60、65，而 使用MBT策略的监管(例如，“不加判断地注意和接受渴望”)不适用于57、66、67。 在此基础上，我们开发了两个简短的、基于网络的、以机制为重点的干预措施：基于CBT的干预措施和 基于MBT的渴求训练调节(ROC-T)58、68、69，参与者重复练习 在酒精图像存在的情况下调节渴望。我们建议评估ROC-T的疗效和它的 通过随机将177名YA重度饮酒者进行4x45分钟的(1)CBT-ROC-T，(2)MBT- ROC-T，或(3)控制(无策略)。酒精使用情况将通过Timeline Followback 70进行测量，为期10周 以及可穿戴的透皮传感器71、72。培训前和培训后，我们将评估认知、情感和 应用ROC任务和功能磁共振成像研究ROC-T的神经机制。目前的项目有可能 显著推进对酗酒、AUD和其他成瘾障碍的机制针对性干预。

Abstract/Project Summary Heavy drinking in young adults (YA) is prevalent, and associated with serious negative consequences including mortality and risk for alcohol use disorders (AUD) 1-7. However, existing interventions have shown modest efficacy 8-14, and innovative interventions are needed. YA interventions have potential for broad impact if they are brief, computerized (especially web-based), and target core neurocognitive mechanisms underlying heavy drinking 14,15. Two such mechanisms are craving and regulation of craving. Defined in DSM-5 as “a strong desire” 16, craving is prospectively associated with and predicts drinking (e.g.,17- 25, including in YAs (e.g., 26-29). Importantly, alcohol-associated cues increase craving 30; such cue-induced craving is also prospectively associated with and predicts drinking(e.g.,31-35), including in YA 32,33,36,37. These data implicate cue-induced craving as a core mechanism underlying drinking 38. Consistently, skills training in regulation of craving is an important feature of many interventions 39-44, including cognitive-behavioral therapy (CBT) 45 and mindfulness-based treatments (MBT) 46,47. Further, regulation of craving directly relates to reductions in craving and drinking, and better treatment outcomes(e.g., 34,41,42,48-52), including in YA 53. These data implicate regulation of craving as a core mechanism underlying change in drinking/abstinence 54. We developed the Regulation of Craving (ROC) task to investigate cognitive, affective, and neural mechanisms associated with craving and its regulation across substances 55-61. In one study, alcohol drinkers were exposed to alcohol images60. On craving trials, they experienced cue-induced craving and exhibited neural activity in regions including ventral striatum and ventromedial prefrontal cortex 62-64. On regulation trials they used a treatment-based strategy to modulate their craving. We found that self-reported craving and craving-related neural activity were significantly reduced during regulation 60. However, across studies we found that the neural mechanisms by which regulation operates depend on the strategy used. Specifically, regulation with CBT strategies (e.g., ‘think of the negative consequences of drinking’) depends on the PFC 56,60,65 while regulation with MBT strategies (e.g., ‘notice and accept craving without judgment’) does not 57,66,67. Based on this, we developed two brief, web-based, mechanism-focused interventions: CBT-based and MBT-based Regulation of Craving Training (ROC-T) 58,68,69, in which participants repeatedly practice regulating craving in the presence of alcohol images. We propose to evaluate the efficacy of ROC-T and its mechanisms by randomizing 177 YA heavy drinkers to 4x45 minute sessions of (1) CBT-ROC-T, (2) MBT- ROC-T, or (3) CONTROL (no strategy). Alcohol use will be measured via Timeline Followback 70 for 10 weeks as well as a wearable transdermal sensor 71,72. Pre- and post-training, we will evaluate cognitive, affective, and neural mechanisms underlying ROC-T using the ROC task and fMRI. The current project has the potential to significantly advance mechanism-targeted interventions for heavy drinking, AUD, and other addictive disorders.