Cerebro-Cerebellar Contributions to Cognitive Function in Drug Addiction

项目概要/摘要 这是一个指导研究科学家发展奖（K 01）的应用程序。的目标 建议的项目是为候选人提供建立独立项目所需的高级技能 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，参与 与个别顾问一起应用培训经验，并参加正在进行的研讨会。具体培训 目标包括：（1）获得额外的临床和教学培训的药物成瘾，（2）培训先进的 神经影像学方法和数据分析，（3）运动障碍的神经学评估培训， 以及（4）负责任地进行研究的培训。培训计划将与以下部门协调执行： 一套基于候选人收集的初步数据的拟议研究报告， 发现大脑的小脑-小脑通路的异常功能与执行功能有关。 美沙酮维持的阿片类药物成瘾者的功能障碍。这些发现与药物直接相关。 成瘾，因为对行为的执行控制的损伤被认为会导致冒险和冲动 行为拟议的研究将描述特定节点的功能和相互依赖性， 小脑-小脑通路，同时也定义了该通路内的中断如何有助于执行 吸毒者，特别是美沙酮维持的阿片类药物使用者的功能障碍。这些研究将结合联合收割机功能磁共振成像 在执行控制任务期间使用其他先进的神经成像方法进行扫描，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考虑到 数据解释，（2）识别同步功能的小脑-小脑通路内的节点，以及（3） 确定为通路服务的白色神经束的完整性。所提议的应用 因此，将确定导致药物成瘾中执行功能障碍的神经机制， 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.