Multimodal Neuroimaging of Cigarette Smoking

描述（由申请人提供）：这是一份通过K25指导定量研究科学家发展奖机制获得5年资助的申请。申请人建议补充他在物理和工程方面的重要训练和研究经验，在药物滥用的神经生物学和药理学方面的多模态神经影像学指导职业发展计划。申请人的短期目标是将他所开发的近红外光谱和功能磁共振成像技术应用于药物滥用研究，并在此过程中加深他对药物滥用神经生物学的了解。申请人的长期目标是在药物滥用成像领域建立专业知识，能够识别该领域的紧迫问题，并开发相应的有效成像技术来研究它们。K25将帮助申请人实现短期目标，并作为迈向长期目标的垫脚石。培训计划包括与拟议的导师进行一对一的培训、实践研究、课程作业、实验室访问、参加国家和国际科学会议以及负责任的研究行为方面的培训。在获得资助的最初几年，申请人将学习神经解剖学、神经生物学和药物滥用课程。本申请的研究部分旨在允许申请人使用多种成像方式（包括近红外光谱和功能性MRI）开发急性吸烟对认知功能影响的成像生物标志物。本提案中概述的三个实验将针对三个与吸烟相关的标记：已知与执行功能和决策有关的前额叶区域的大脑激活；静息状态网络被认为与自我监控有关；大脑活动模式与烟草渴望以及通过吸烟减少烟草渴望有关。研究这些标志物与吸烟前后、吸烟期间和吸烟之间的持续相互作用将有助于开发和客观评估新的治疗方法。申请人开发的新技术解决了严重限制BOLD fMRI在许多药物滥用研究中的应用的混淆信号。他们允许近红外光谱和功能磁共振成像监测不间断的吸烟。通过这些实验，申请人将获得临床研究各方面的技能，并在人类药物滥用研究的实际问题上获得经验。实验将在麦克林医院脑成像中心进行，该中心拥有一流的设备和工作人员，可以在药物滥用方面进行复杂的近红外光谱和功能磁共振成像实验。综合培训和研究计划将使申请人能够将其研究从技术开发转向生物和制药应用。建议的指导培训计划将帮助申请人成为一名独立调查员，开发和应用新的成像技术和分析工具来研究药物滥用。

DESCRIPTION (provided by applicant): This is a request for 5 years of funding through the K25 Mentored Quantitative Research Scientist Development Award mechanism. The applicant proposes to supplement his significant training and research experience in physics and engineering with a mentored career development program in multimodal neuroimaging of the neurobiological and pharmacological aspects of substance abuse. The applicant's short-term goal is to apply the techniques he has developed with NIRS and fMRI to substance abuse studies, and during this process deepen his knowledge of the neurobiology of substance abuse. The applicant's long-term goal is to establish expertise in the field of substance abuse imaging, to be able to identify pressing problems in the field, and develop corresponding effective imaging techniques to study them. The K25 will help the applicant achieve the short-term goal and serve as a stepping-stone for the long-term goal. The training plan includes one-on-one training sessions with proposed mentors, hands-on research, course work, laboratory visits, attendance at national and international scientific meetings, and training in responsible conduct of research. During the early years of the grant, the applicant will take courses in neuroanatomy, neurobiology and substance abuse. The research component of this proposal is structured to allow the applicant to develop imaging biomarkers of acute smoking effects on the cognitive functions using multiple imaging modalities, including near-infrared spectroscopy and functional MRI. The three experiments outlined in this proposal will target three smoking-related markers: brain activation in prefrontal areas known to be involved with executive function and decision-making; the resting state networks thought to be involved with self-monitoring; and the patterns of brain activation associated with tobacco craving and its reduction through smoking. Studying continuous interactions between these markers and tobacco smoking before, during and after smoking will aid in developing and objectively evaluating new treatments. The new techniques developed by the applicant address confounding signals that have severely curtailed the application of BOLD fMRI to a number of substance abuse studies. They allow uninterrupted smoking to be monitored by NIRS and fMRI. Through these experiments, the applicant will acquire skills in all aspects of clinic research studies and give him experience in the practical issues of human substance abuse studies. The experiments will be performed at the McLean Hospital Brain Imaging Center, which has excellent facilities and staff for performing sophisticated NIRS and fMRI experiments in substance abuse. The integrated training and research plans will equip the applicant to shift his research from technology development to biological and pharmaceutical applications. The proposed mentored training plan will assist the applicant to become an independent investigator developing and applying new imaging techniques and analytical tools to study substance abuse.