Cognitive Reappraisal for Mitigating Incubation of Cocaine Cue-Reactivity

摘要 可卡因的使用在全国范围内很普遍。根据一项全国性的调查，超过2.5%的个人人口 12岁及以上报告在过去一年中使用可卡因或可卡因，占10,000多人死于 可卡因过量。最近的数据表明，新冠肺炎大流行加剧了美国人对药物的使用 美国。只有一小部分可卡因吸毒者寻求正式治疗，即使是在那些 世卫组织的复发率仍然高得令人不安，一些研究报告复发率高达90%，12个月 治疗后。成瘾个体的复发被认为是由于再次接触到 以前都与吸毒有关。在长期吸毒的过程中，这些线索被提供给 增强注意力(或注意力偏向)，这已被证明能促进被激发的唤醒，最终导致强迫症 寻求毒品或复发。我们使用了晚期正电位(LPP)，这是一种源于脑电的动机标记物 唤醒表明，与通常认为的不同，对药物线索(或线索反应)的唤醒增加(或孵化) 在禁欲的前六个月。这种线索-反应的孵化被认为是不成比例的 成瘾者具有高度的复发易感性。我们最近获得的跟踪数据显示，上瘾 个体能够通过以下方式下调药物线索反应性(通过LPP幅度的降低来明显) 认知重新评估(一种情绪调节技术)训练，然后导致自发性降低 对药物线索的注意力偏向(使用眼球跟踪进行量化)。在这里，我们建议将这两个部分整合在一起 测试认知再评价训练是否可以减少药物线索-反应潜伏期的证据(目标1) 和改善临床结果(例如，减少对可卡因的渴望和延长可卡因戒断时间；目标2) 可卡因使用障碍(ICUD)患者的前6个月戒酒。我们将进一步探讨是否 对药物线索的注意偏向的改变和/或线索反应潜伏期的钝化跟踪治疗反应 并预测6个月随访的临床结果(探索性目标)。为此，我们建议招收 126名iCUD，其中一半将随机接受认知重新评估训练，另一半将 相反，要完成一项控制任务。在这项纵向研究中，参与者将在1周内完成这些程序， 禁欲开始后1个月、3个月和5个月，然后在一个月后(在6个月后)回来 禁欲启动)，用于评估临床结果。因此，这项新颖的研究旨在架起 通过推进实验室和临床对循证干预的基本机理的理解来 为跟踪治疗反应和预测成瘾结果提供认知标记物。成功 这项研究的完成将为进一步的基础和临床研究奠定基础，这些研究将检查其他 可能的机制，并潜在地使用相同的框架对类似的神经认知检查 对其他物质使用障碍以及其他行为成瘾的认知干预。

SUMMARY Cocaine use is endemic nationwide. According to a national survey, over 2.5% of the population of individuals 12 years and older reported crack or cocaine use in the past year, accounting for over 10,000 deaths related to cocaine overdose. Recent data suggests that the COVID-19 pandemic has exacerbated substance use in the United States. Only a small minority of cocaine users seek formal treatment for their addiction, and even in those who do, the relapse rate remains disturbingly high with some studies reporting rates as high as 90%, 12 months after treatment. Relapse in addicted individuals is presumed to precipitate from the re-exposure to cues that were previously associated with drug use. Over the course of chronic drug use, these cues are afforded enhanced attention (or attention-bias), which has shown to promote motivated arousal, culminating in compulsive drug-seeking or relapse. We have used the late positive potential (LPP), an EEG-derived marker of motivated arousal to show that, unlike commonly believed, arousal to drug cues (or cue-reactivity) increases (or incubates) during the first six months of abstinence. Such incubation of cue-reactivity is posited to confer disproportionately high relapse vulnerability in addicted individuals. Our recently acquired follow-up data show that addicted individuals are able to down-regulate drug cue-reactivity (as evident via a decrease in LPP amplitude) via cognitive reappraisal (an emotion-regulation technique) training, which then leads to a reduction in spontaneous attention-bias to drug cues (quantified using eye-tracking). Here, we propose to integrate the two pieces of evidence to test whether cognitive reappraisal training can reduce the incubation of drug cue-reactivity (Aim 1) and improve clinical outcomes (e.g., reduce craving and prolong cocaine abstinence duration; Aim 2) during the first 6 months of abstinence in individuals with cocaine use disorder (iCUD). We will further explore whether changes in attention-bias to drug cues and/or blunting of incubation of cue-reactivity tracks treatment response and predicts clinical outcomes at 6 months follow-up (exploratory aim). For this purpose, we propose to enroll 126 iCUD, half of whom will be randomized to undergo cognitive reappraisal training and the other half will instead complete a control task. In this longitudinal study, participants will complete these procedures at 1-week, 1-, 3-, and 5-months post abstinence initiation, and will then come back one month after (at 6 months post abstinence initiation) for the assessment of clinical outcomes. Thus, this novel study aims to bridge between the lab and the clinic by advancing basic mechanistic understanding of a novel evidence-based intervention to provide cognitive markers for tracking treatment response and predicting outcomes in addiction. Successful completion of this study would lay the foundation for further basic and clinical studies that will examine other putative mechanisms and potentially also use the same framework for the neurocognitive examination of similar cognitive interventions in other substance use disorders as well as in other behavioral addictions.