Cerebro-Cerebellar Contributions to Cognitive Function in Drug Addiction

描述（由申请人提供）：这是指导研究科学家发展奖（K01）的申请。拟议项目的目标是为候选人提供使用先进的神经影像方法建立独立的成瘾研究计划所需的高级技能。候选人提出一个全面的培训计划，结合导师监督的教学指导、正式课程、与个人顾问一起参加应用培训经验以及参加正在进行的研讨会。具体培训目标包括：(1) 获得额外的毒瘾临床和教学培训，(2) 先进神经影像方法和数据分析培训，(3) 运动障碍神经学评估培训，(4) 负责任的研究行为培训。该培训计划将与一组拟议的研究协调执行，这些研究基于候选人收集的初步数据，该研究发现大脑脑-小脑通路的异常功能与美沙酮维持的阿片类药物成瘾者的执行功能障碍有关。这些发现与毒瘾直接相关，因为对行为的执行控制受损被认为会导致危险和冲动行为。拟议的研究将描述脑-小脑通路内特定节点的功能和相互依赖性，同时还定义该通路内的破坏如何导致吸毒者，特别是美沙酮维持的阿片类药物使用者的执行功能障碍。这些研究将执行控制任务期间的功能磁共振成像扫描与其他先进的神经影像方法结合起来，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）识别脑小脑通路内同步功能的节点，以及（3）确定促进该通路的白质神经束的完整性。因此，拟议的申请将确定导致药物成瘾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中建立独立的研究生涯。 公共卫生相关性：本研究的目的是检查识别与毒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，其结果有可能确定毒瘾和复发治疗干预的重要目标。

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.