Cerebro-Cerebellar Contributions to Cognitive Function in Drug Addiction

项目摘要/摘要 这是一份导师研究科学家发展奖(K01)的申请书。的目标是 提议的项目是为候选人提供建立独立计划所需的高级技能 使用先进的神经成像方法进行成瘾研究。候选人提出了一项全面的 培训计划，结合由她的导师监督的教学指导，正式的课程作业，参与 与个别顾问的应用培训经验，并参加正在进行的研讨会。具体培训 目标包括：(1)获得更多的药物成瘾的临床和教学培训；(2)高级培训 神经成像方法和数据分析，(3)运动障碍的神经学评估培训， 以及(4)负责任的研究行为方面的培训。培训计划的执行将与 一组建议的研究研究，基于候选人收集的初步数据， 发现大脑大脑-小脑通路功能异常与执行有关 美沙酮维持阿片成瘾吸毒者的功能障碍。这些发现与毒品有直接关系。 上瘾是因为对行为的执行控制受损被认为会导致危险和冲动 行为。拟议的研究将表征内部特定节点的功能和相互依赖 大脑-小脑通路，同时也定义了这一通路内的干扰如何有助于执行 吸毒者的功能障碍，特别是美沙酮维持的阿片类药物使用者。这些研究将结合功能磁共振成像 在执行控制任务期间使用其他高级神经成像方法进行扫描，这些方法将(1)评估 基线生理状态，以便神经生理学中的基本组差异可以被考虑到 数据解释，(2)确定大脑-小脑通路中功能同步的节点，以及(3) 确定为通路提供辅助的白质神经束的完整性。建议的应用程序 因此，将确定导致吸毒成瘾时执行功能障碍的神经机制，并在 同时，使候选人能够在药物成瘾研究方面建立独立的研究生涯。

Project Summary/Abstract 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.