Novel Use of fMRI to Study Substance Abuse Problems

描述(由申请人提供)： 这是通过K25量化指导研究职业发展奖机制申请五年资金的请求。这位候选人是一名成像物理学家和统计学家，她提出了一项强化培训和研究计划，以促进她作为一名跨学科科学家的成长，能够为开发新出现的功能磁共振成像(FMRI)技术来研究药物滥用问题提供支持。培训计划结合了课程作业、实验室访问和会议，以提供神经科学和药物滥用领域的正式培训，这既将补充研究项目的经验，也将加快研究项目的成功完成。使用功能磁共振成像来研究药物滥用问题仍然相对少见，但总的来说，这一应用前景广阔，功能磁共振成像方法--包括研究设计和数据/统计分析--仍在以非常快的速度发展；对于希望利用功能磁共振成像但没有成像背景来选择适当研究设计的研究人员来说，这可能是一个令人难以置信的障碍。该研究计划的重点是优化新的功能磁共振成像技术，以研究青少年和成人使用大麻的各个方面，并将这些鲜为人知但极其灵活的方法传播给药物滥用研究界。第一个项目调查了吸食大麻的青少年和成年人对视觉、听觉和嗅觉药物线索的反应差异。主观反应(线索诱导的大麻渴求的自我报告)和生理反应(皮肤温度、心率和皮肤电导)将被记录并使用多元统计方法进行分析。两组受试者的反应也将与健康匹配的对照组受试者的反应进行比较。第二个项目是一项与事件相关的功能磁共振成像研究，研究线索诱导的渴求对青少年和成年大麻使用者(也将测试健康的匹配对照组受试者)的古怪任务表现的影响。研究设计和数据分析策略将允许评估渴望的两个不同方面，每个方面都在不同的时间尺度上。第三个项目是一项药理学功能磁共振成像(PhMRI)研究，将解决急性服用大麻如何影响成年大麻使用者的大脑活动的问题。将对phMRI方法进行优化，以平衡大麻笨拙的药代动力学特性和微小且随时间变化的认知效应的影响。这三个项目加在一起，将构成候选人的宝贵培训经验，同时展示新的功能磁共振成像技术在研究药物滥用问题和更好地了解大麻对青少年和成年人的影响方面的多功能性。

DESCRIPTION (provided by applicant): This is a request for five years of funding through the K25 Quantitative Mentored Research Career Development Award mechanism. The candidate, an imaging physicist and statistician, has proposed an intensive training and research program to facilitate her growth as an interdisciplinary scientist, capable of obtaining support for the development of newly emerging functional magnetic resonance imaging (fMRI) techniques to study substance abuse problems. The training plan reflects a combination of coursework, laboratory visits, and meetings to provide formal training in the areas of neuroscience and substance abuse that will both complement the experience of and expedite the successful completion of the research projects. The use of fMRI to study drug abuse problems is still relatively uncommon, but in general, holds great promise for this application, fMRI methods - both study designs and data/statistical analyses - are still evolving at a very rapid pace; this can be an incredible obstacle for investigators who wish to utilize fMRI but do not have the imaging background to select an appropriate study design. The research plan focuses on the optimization of novel fMRI techniques to study aspects of marijuana use in adolescents and adults and on the dissemination of these lesser known, yet incredibly flexible, methods to the substance abuse research community. The first project investigates differences in reactivity to visual, audio, and olfactory drug cues between adolescents and adults who use marijuana. Subjective responses (self-reports of cue-induced marijuana craving) and physiological responses (skin temperature, heart rate, and skin conductance) will be recorded and analyzed using multivariate statistical methods. Responses for both groups will also be compared with responses from healthy matched control subjects. The second project is an event-related fMRI study of the effects of cue induced craving on performance of an oddball task in adolescent and adult marijuana users (healthy matched control subjects will also be tested). The study design and data analysis strategy will permit the assessment of two different aspects of craving, each over a different time scale. The third project is a pharmacological fMRI (phMRI) study that will tackle the question of how acute administration of marijuana effects brain activity in adult marijuana users. The phMRI methods will be optimized to balance the impact of the unwieldy pharmacokinetic properties of marijuana and the small and temporally variable cognitive effects. All together, these three projects will constitute an invaluable training experience for the candidate while demonstrating the versatility of newer fMRI techniques in studying substance abuse problems and providing a better understanding of marijuana effects in adolescents and adults.