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

项目 1：正念如何调节中度至重度饮酒者的渴望和大脑网络

• 批准号: 10310700
• 负责人: Paul Laurienti
• 金额: $ 37.6万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-10 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10310700
• 关键词: Abstinence; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; American; Americas; Amygdaloid structure; Anterior; Anxiety; Behavior Therapy; Behavioral; Behavioral Mechanisms; Brain; Brain region; Cellular Phone; Cessation of life; Characteristics; Clinical; Clinical Treatment; Clinical Trials; Corpus striatum structure; Development; Disease; Ecological momentary assessment; Educational Intervention; Effectiveness; Environment; Exhibits; Female; Future; Incidence; Individual; Informal Social Control; Intervention; Intoxication; Lead; Measures; Medial; Meditation; Methods; Modeling; Neurobiology; Outcome; Participant; Pathway Analysis; Patient Self-Report; Patients; Placebo Control; Population; Prefrontal Cortex; Preventive treatment; Process; Property; Questionnaires; Randomized; Recording of previous events; Regimen; Relapse; Reporting; Risk; Sampling; Single-Blind Study; Stress; Structure of superior frontal gyrus; Surgeon; Symptoms; Technology; Time; Training; Ventral Striatum; Withdrawal; addiction; alcohol craving; alcohol misuse; alcohol research; alcohol use disorder; base; behavior measurement; behavioral phenotyping; craving; design; deter alcohol use; drinking; effective therapy; experience; forest; interest; male; mental training; mindfulness; mindfulness intervention; mindfulness meditation; negative affect; neural circuit; neuroimaging; neuromechanism; novel; pain reduction; relating to nervous system; resilience; response; statistics; trait

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.

项目摘要 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并不完全 明白尽管美国每年有88,000人死于酒精滥用， 目前可用的干预措施的有效性不太理想，并表现为复发 发生在70%的治疗患者中。很明显，我们必须更好地了解AUD的神经生物学 脆弱性，以便在疾病过程的早期识别患者，并采用适当的新治疗方法 可以开发。有一种逐渐被接受的成瘾三阶段模型，它基于一种反复出现的 暴饮暴食/中毒的循环，随后是退缩/负面影响，最终是全神贯注/预期 进一步使用（渴望）。该项目将重点关注渴望作为澳元脆弱性的潜在标志，因为它是 AUD复发的主要预测因素。第一个目的是为了表征行为表型， 中高度饮酒者（女性1-3）与高渴望相关的脑网络特性 饮酒/天，雄性2-4饮酒/天）。参与者必须在一周的大部分时间内饮酒，但不能有任何病史。 或目前符合AUD的标准。利用iPhone的生态瞬时评估（EMA）方法 技术将被用来评估渴望在真实的时间和在参与者的自然环境中， 正常饮酒日以及戒酒期间。功能性神经成像和大脑网络分析将 可以用来研究渴望和大脑连接之间的联系。假设1）个人 高酒精渴望体验（ACE）分数将有更高的EMA渴望措施，和2）高 ACE人群的内侧前额叶皮层（mPFC）和后额叶皮层之间的连接水平较高， 默认模式网络（DMN）和mPFC与腹侧纹状体之间的低水平效率， 杏仁核目标2和3将评估随机化对正念冥想干预的影响 与虚假的正念干预相比， 中度至重度饮酒者的渴望。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。它是假设 正念冥想不仅会显着降低EMA的渴望措施， 增加mPFC和后DMN之间的连接，并增加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 通过理解支持冥想相关减少的相应机制来确定临床结果 对酒精的渴望作为脆弱性指标的潜在渴望行为标记的识别 可能导致现实世界的干预措施，以防止澳元。