Cognitive Neuroscience of Decision Making in Recovery from Alcoholism

描述（由申请人提供）：对酗酒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明确证据。此外，确定人们如何改变的困难不仅限于寻求治疗的人，也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巨大挑战之一。最近，人们越来越关注跨学科研究的必要性，认为行为改变是一个人的环境、思想和行为、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。本K02申请旨在促进申请人在酗酒康复方面的跨学科研究进展。基于申请人在研究行为治疗的作用机制方面的背景，本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有关。该提案的目标是获得足够的决策理论、神经科学和神经影像学知识，以允许候选人进行独立研究，检查思维过程和大脑活动与问题饮酒者饮酒变化之间的联系。为了实现这些目标，将遵循详细的职业发展计划，包括正式的课程，研讨会，指导阅读，与特定内容领域的专家进行持续磋商，以及对现有数据集的经验工作。加州大学洛杉矶分校神经精神表型组学联盟（CNP）是一个重要的机构资源，将促进申请人努力实现这些目标。CNP是一个跨学科的、全校范围的项目，由来自精神病学、神经学、神经生物学、心理学和计算机科学等领域的52名研究人员组成，他们合作并共享数据。CNP与拟议的职业发展计划特别相关的具体方面是，它将冲动控制作为其两大认知表型领域之一，它收集了500个人的功能磁共振成像电池数据，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，以获得执行决策和功能磁共振成像程序的实践经验，并分析酒精使用，决策和大脑活动之间关系的数据。作为程序化研究的第一步，我们提出了一项采用重复测量纵向设计的随机对照试验，以检验在未接受治疗的重度饮酒者中，酒精使用量的减少与大脑活动变化和决策过程中对奖励的敏感性的关系。参与者（n=114）包括男性和女性。在基线、1个月和3个月的随访中进行基于实验室fmri的范式，以评估决策任务期间的大脑活动。在相同的3个月期间，将使用每日监测程序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。基线评估后，参与者将被随机分配到4期动机干预组或候补对照组。数据将分析与结构方程建模和先进的动态系统建模。据推测，酒精使用的减少将从一系列相互关联的亲改变过程中预测出来，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降低，以及非饮酒活动的增加。这项复杂系统的纵向研究提供了巨大的希望，极大地提高了我们对行为改变机制的理解，并为促进普通人群中酗酒者的这种改变提供了信息。

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.