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 Wake Forest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）脆弱性和韧性的神经生物学底物尚未完全 理解。尽管滥用酒精每年在美国造成88,000人死亡，但 当前可用的干预措施的有效性不足以理解，并通过复发证明 在多达70％的治疗患者中发生。显然，我们必须更好地了解AUD的神经生物学 脆弱性，以便可以在疾病过程的早期发现患者并进行适当的新治疗 可以开发。有一个基于反复出现的成瘾的三阶段成瘾模型 暴饮暴食/中毒的循环，其次是戒断/负面影响，并最终关注/预期 进一步使用（渴望）。该项目将侧重于渴望作为AUD漏洞的潜在标记，因为它是 AUD复发的主要预测指标。第一个目的旨在表征行为表型和 大脑网络特性与高度饮酒者的高渴望相关（女性1-3 每天喝酒，男性2-4饮料/天）。参与者必须在一周的大部分时间喝酒，但不能有任何历史 或目前符合AUD的标准。使用iPhone的生态瞬时评估（EMA）方法 技术将用于评估实时的渴望以及参与者的自然环境 正常的饮酒日以及戒酒期间。功能性神经影像学和大脑网络分析将 用于检查渴望与大脑连通性之间的关联。假设1）个人 凭借高酒精的经验（ACE）分数将具有更高的EMA渴望度量，而2）高 ACE种群将在内侧前额叶皮层（MPFC）和后部之间具有高水平的连通性 MPFC和腹侧纹状体之间的默认模式网络（DMN）和低水平的效率 杏仁核。目标2和3将评估随机化对正念冥想干预的影响 相对于与高有关的行为和大脑特征相关的虚假正念干预 渴望饮酒中等饮酒者。这将是安慰剂控制的正念冥想研究 检查支持渴望酒精的行为和神经机制。假设 正念冥想不仅会显着降低EMA的渴望措施，而且会减少 MPFC和DMN后DMN之间的连通性，并增加了从MPFC到腹侧的连通性 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 通过了解支持冥想相关降低的相应机制来实现临床结果 渴望酒精。识别渴望作为脆弱性指标的行为标记 可能导致实际干预措施以防止AUD。