Cerebro-Cerebellar Contributions to Cognitive Function in Drug Addiction

描述(申请人提供)：这是一个导师研究科学家发展奖(K01)的申请书。拟议项目的目标是为候选人提供所需的高级技能，以利用先进的神经成像方法建立一个独立的成瘾研究项目。候选人提出了一个全面的培训计划，结合了她的导师指导的教学、正式的课程作业、与个别顾问一起参加应用培训经验，以及参加正在进行的研讨会。具体的培训目标包括：(1)获得更多的药物成瘾的临床和教学培训；(2)先进的神经成像方法和数据分析培训；(3)运动障碍的神经学评估培训；以及(4)负责任的研究工作培训。培训计划将与一组拟议的研究相协调，这些研究基于候选人收集的初步数据，这些研究发现，大脑大脑-小脑通路的异常功能与美沙酮维持阿片成瘾吸毒者的执行功能障碍有关。这些发现与吸毒成瘾直接相关，因为对行为的执行控制受损被认为会导致危险和冲动的行为。这项拟议的研究将描述大脑-小脑通路中特定节点的功能和相互依赖性，同时还将确定这一通路中的干扰如何导致吸毒者，特别是美沙酮维持阿片类药物使用者的执行功能障碍。这些研究将把执行控制任务期间的fMRI扫描与其他先进的神经成像方法结合起来，这些方法将(1)评估基线生理状态，以便在数据解释中考虑神经生理学的基本群体差异，(2)识别大脑-小脑路径内同步运行的节点，以及(3)确定支持该路径的白质神经束的完整性。因此，这项拟议的申请将确定导致吸毒成瘾时执行功能障碍的神经机制，同时使候选人能够在吸毒成瘾研究中建立独立的研究生涯。 公共卫生相关性：这项研究的目的是检查识别与药物成瘾有关的大脑异常的措施。这项研究与公共卫生的相关性在于，研究结果有可能为药物成瘾和复发的治疗干预确定重要的目标。

DESCRIPTION (provided by applicant): This is an application for a Mentored Research scientist Development Award (K01). The goal of the proposed project is to provide the Candidate with advanced skills needed to establish an independent program of addiction research using advanced neuroimaging methods. The Candidate proposes a comprehensive training plan, combining didactic instruction overseen by her mentors, formal coursework, participation in applied training experiences with individual advisors, and participation in ongoing seminars. Specific training goals include: (1) gaining additional clinical and didactic training in drug addiction, (2) training in advanced neuroimaging methods and data analysis, (3) training in the neurological assessment of movement disorders, and (4) training in the responsible conduct of research. The training plan will be executed in coordination with a proposed set of research studies that are based upon preliminary data collected by the Candidate, which found that abnormal function of the brain's cerebro-cerebellar pathway was associated with executive dysfunction in methadone-maintained opioid-addicted drug users. These findings are directly relevant to drug addiction because impairments of executive control over behavior are thought to lead to risky and impulsive behavior. The proposed research will characterize the function and interdependence of specific nodes within the cerebro-cerebellar pathway, while also defining how disruptions within this pathway contribute to executive dysfunction in drug users, specifically methadone-maintained opioid users. The studies will combine fMRI scanning during executive control tasks with other advanced neuroimaging methods that will (1) assess baseline physiological states so that fundamental group differences in neurophysiology can be factored into the data interpretation, (2) identify nodes within the cerebro-cerebellar pathway that function in synchrony, and (3) determine the integrity of the white matter nerve bundles that subserve the pathway. The proposed application will, therefore, identify neural mechanisms that contribute to executive dysfunction in drug addiction and, at the same time, enable the Candidate to establish an independent research career in the study of drug addiction. PUBLIC HEALTH RELEVANCE: The aim of this study is to examine measures that that identify brain abnormalities involved in drug addiction. The relevance of this research to public health is that results have the potential to identify important targets for therapeutic interventions in drug addiction and relapse.