Cognitive Neuroscience of Decision Making in Recovery from Alcoholism

描述(由申请人提供)：关于酒精中毒行为治疗的研究几乎没有提供关于治疗如何影响积极行为改变的确凿证据。此外，确定人们如何改变的困难不仅限于寻求治疗的人，而且普遍适用于非寻求治疗的人。行为改变机制的识别正在成为成瘾研究的重大挑战之一。最近，人们越来越多地关注跨学科研究的必要性，这些研究将行为变化视为一个人的环境、思想和行为以及大脑功能和生物学之间复杂相互作用的结果。这样的研究为确定人们如何改变他们的饮酒行为提供了巨大的机会。这份K02申请旨在促进申请者在戒酒方面的跨学科研究进展。基于申请者在研究行为治疗的作用机制方面的背景，这项申请的目标是获得认知神经科学方面的专业知识，因为它与改变一个人的酒精使用情况有关。这项建议的目的是获得足够的决策理论、神经科学和神经成像知识，使候选人能够进行独立研究，检查问题饮酒者的思维过程和大脑活动与酒精使用变化之间的联系。为了实现这些目标，将遵循一项详细的职业发展计划，其中包括正式课程、讲习班、定向阅读、与特定内容领域专家的持续协商以及对现有数据集的体验性工作。一个重要的机构资源，将促进申请人的努力，以实现这些目标是加州大学洛杉矶分校的神经精神表现学联盟(CNP)。CNP是一个跨学科的校园范围的努力，由52名调查人员组成，成员来自精神病学、神经学、神经生物学、心理学和计算机科学领域，合作和共享数据。与拟议的职业发展计划特别相关的CNP的具体方面是，其重点是冲动控制，作为其两个广泛的认知表型领域之一，它收集了500人的功能磁共振电池数据，以及收集了参与者的酒精使用数据。候选人将与CNP和合作者一起工作，获得在执行决策和功能磁共振程序以及分析酒精使用、决策和大脑活动之间关系的数据方面的实践经验。作为程序性研究的第一步，一项采用重复测量纵向设计的随机对照试验被提出，以检查未接受治疗的酗酒者酒精使用量的减少，作为大脑活动变化和决策过程中对奖励的敏感性的函数。参与者(n=114)将包括男性和女性。基于实验室功能磁共振成像的范例将在基线、1个月和3个月的随访中进行，以评估决策任务期间的大脑活动。在相同的3个月期间，每天的监测程序将被用来捕捉实时决策过程、酒精使用情况以及酒精使用的感知影响。在基线评估之后，参与者将被随机分配到4个疗程的动机干预或等待名单控制组。数据将通过结构方程建模和高级动态系统建模进行分析。假设酒精使用量的减少将通过一系列相互关联的促改变过程来预测，这些过程包括与渴望和冲动相关的大脑活动的减少，决策过程中酒精奖励价值的减少，以及不饮酒活动的增加。这项对复杂系统的纵向研究提供了极大的希望，可以极大地提高我们对行为变化机制的理解，并为在普通人群中促进这种变化的努力提供信息。

DESCRIPTION (provided by applicant): Research on behavioral treatments for alcoholism has provided little definitive evidence about how treatment influences positive behavior change. Moreover, the difficulty of identifying how people change is not limited to treatment seekers but generalizes to non-treatment seekers. The identification of mechanisms of behavior change is emerging as one of the great challenges to addiction research. Recently, increased attention has been given to the need for cross-disciplinary research that views behavior change as the result of a complex interplay between one's environment, thoughts and behaviors, and brain function and biology. Such research provides tremendous opportunities to identify how people change their alcohol use behavior. This K02 application seeks to promote the applicant's progression into transdisciplinary research on recovery from alcoholism. Building on the applicant's background in studying the mechanisms of action of behavioral treatments, the goal of this application is to gain expertise in cognitive neuroscience as it relates to efforts to change one's alcohol use. The objectives of this proposal are to acquire sufficient knowledge of decision theory, neuroscience, and neuroimaging to permit the candidate to conduct independent research that examines linkages between thought processes and brain activity with changes in alcohol use among problem drinkers. To achieve these objectives a detailed career development plan will be followed that entails formal coursework, workshops, directed readings, ongoing consultations with experts in specific content areas, and experiential work on existing datasets. An important institutional resource that will facilitate the applicant's efforts towards achieving these objectives is the UCLA Consortium for Neuropsychiatric Phenomics (CNP). The CNP is an interdisciplinary, campus-wide effort comprised of 52 investigators with members from the fields of psychiatry, neurology, neurobiology, psychology and computer science collaborating and sharing data. The specific aspects of the CNP especially relevant to the proposed career development plan are its focus on impulse control as one of its two broad cognitive phenotypic domains, its collection of data on an fMRI battery for 500 individuals, and its collection of data on alcohol use by participants. The candidate will work with the CNP and collaborators to receive practical experience in performing decision making and fMRI procedures and analyzing data on relationships between alcohol use, decision making, and brain activity. As a first step in a programmatic line of research, a randomized controlled trial using a repeated measures longitudinal design is proposed to examine decreases in alcohol use among non-treatment seeking heavy drinkers as function of change in brain activity and sensitivity to reward during decision making. Participants (n=114) will include both men and women. A laboratory fMRI-based paradigm will be conducted at baseline, 1-month, and 3-month follow-ups to assess brain activity during decision making tasks. Daily monitoring procedures across the same 3-month period will be used to capture real-time decision making processes, alcohol use, and the perceived effects of alcohol use. After the baseline assessment participants will be randomly assigned to either a 4-session motivational intervention or a wait-list control group. Data will be analyzed with structural equation modeling and with advanced dynamic systems modeling. It is hypothesized that reductions in alcohol use will be predicted from a cascade of interrelated pro-change processes that include decreases in brain activity associated with craving and impulsivity, decreased reward value of alcohol during decision making, and increased non-drinking activities. This longitudinal study of complex systems offers great promise to dramatically improve our understanding of mechanisms of behavior change and to inform efforts to promote this change among heavy drinkers in the general population.