Project 1: How mindfulness modulates craving and brain networks in moderate-to-heavy drinkers

项目总结 维克森林转化酒精研究中心(WF-TARC)的科学前提是 导致酒精使用障碍(AUD)脆弱性和恢复力的神经生物学底物尚未完全 明白了。尽管在美国，酒精滥用每年导致8.8万人死亡，但 目前可用的干预措施的有效性并不理想，复发证明了这一点 发生在高达70%的接受治疗的患者中。很明显，我们必须更好地了解澳门氏症的神经生物学。 脆弱性，使患者能够在疾病过程的早期被识别并获得适当的新疗法 可以被开发出来。有一种越来越被接受的成瘾三阶段模型，它基于一种反复出现的 狂欢/沉醉的循环，然后是戒断/负面影响，最终是全神贯注/期待 进一步使用(渴望)。该项目将重点关注作为AUD漏洞的潜在标记的渴望，因为它是 澳门氏症复发的主要预测因子。第一个目标是描述行为表型和 与中高酒精饮酒者高度渴求相关的脑网络特性(女性1-3 饮品/天，男性2-4杯/天)。参与者必须在一周中的大部分时间饮酒，但不能有任何病史 澳元的澳元的，或目前符合澳元标准的利用iPhone的生态瞬时评估(EMA)方法 技术将被用来在实时和在参与者的自然环境中评估渴望 正常饮酒日，以及禁欲期间。功能神经成像和脑网络分析将 用来检验渴望和大脑连通性之间的联系。人们假设1)个人 酒精渴望体验(ACE)得分越高，EMA渴望的测量就越高，2)高 ACE人群将在内侧前额叶皮质(MPFC)和后部之间具有高水平的连接 默认模式网络(DMN)和mPFC和腹侧纹状体之间的低效率水平以及 杏仁核。目标2和目标3将评估正念冥想干预的随机化效果 而不是虚假的正念干预，对与高水平睡眠相关的行为和大脑特征进行干预 对中高酒精饮酒者的渴求。这将是第一个安慰剂控制的正念冥想研究。 研究支持酒精渴求的行为和神经机制。据推测， 正念冥想不仅会显著减少EMA对欲望的测量，而且还会减少 MPFC和后DMN之间的连接以及增加从mPFC到腹侧的连接 纹状体和杏仁核。该项目有可能指导未来临床试验的发展，以更好地 通过了解支持冥想相关减少的相应机制来确定临床结果 对酒精的渴求。确定潜在渴望的行为标记物作为脆弱性的指示器 可能会导致现实世界的干预措施来预防澳元。

PROJECT SUMMARY The scientific premise of the Wake Forest Translational Alcohol Research Center (WF-TARC) is that the neurobiological substrates that contribute to alcohol use disorder (AUD) vulnerability and resilience are not fully understood. Despite the fact that alcohol misuse contributes to 88,000 deaths in America each year, the effectiveness of currently available interventions is less than desirable and is demonstrated by relapse occurring in up to 70% of treated patients. It is clear that we must better understand the neurobiology of AUD vulnerability so that patients can be identified early in the disease process and appropriate novel treatments can be developed. There is a growingly accepted three-stage model of addiction that is based on a recurring cycle of binge/intoxication, followed by withdrawal/negative affect, and ultimately preoccupation/anticipation of further use (craving). This project will focus on craving as a potential marker for AUD vulnerability as it is the primary predictor of AUD relapse. The first aim is designed to characterize the behavioral phenotypes and brain network properties associated with high craving in moderate-high alcohol drinkers (females 1-3 drinks/day, males 2-4 drinks/day). Participants must drink most days of the week but cannot have any history of, or currently meet criteria for, AUD. Ecological momentary assessment (EMA) methods utilizing iPhone technology will be used to assess craving during real time and in the participant's natural environment during normal drinking days, as well as during abstinence. Functional neuroimaging and brain network analyses will be used to examine associations between craving and brain connectivity. It is hypothesized that 1) individuals with high Alcohol Craving Experience (ACE) scores will have higher measures of EMA craving, and 2) the high ACE population will have high levels of connectivity between medial prefrontal cortex (mPFC) and posterior default-mode network (DMN) and low levels of efficiency between the mPFC and the ventral striatum and amygdala. Aims 2 and 3 will evaluate the effects of randomization to mindfulness meditation intervention versus a sham mindfulness intervention on the behavioral and brain characteristics associated with high craving in moderate-high alcohol drinkers. This will be the first placebo-controlled mindfulness meditation study to examine the behavioral and neural mechanisms supporting alcohol craving. It is hypothesized that mindfulness meditation will not only significantly reduce EMA measures of craving, but will decrease connectivity between the mPFC and posterior DMN and increase connectivity from the mPFC to the ventral striatum and amygdala. This project has the potential to guide the development of future clinical trials to better target clinical outcomes by understanding corresponding mechanisms supporting meditation-related reductions in alcohol craving. The identification of behavioral markers underlying craving as an indicator of vulnerability could lead to real-world interventions to prevent AUD.