Multimodal Neuroimaging of Cigarette Smoking

描述(由申请者提供)：这是一份通过K25导师定量研究科学家发展奖机制提供5年资助的申请。申请人建议在物理学和工程学方面的重要培训和研究经验的基础上，辅以一项关于药物滥用的神经生物学和药理学方面的多模式神经成像的指导职业发展计划。申请者的短期目标是将他利用近红外光谱和功能磁共振技术开发的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的神经生物学的知识。申请者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这些问题。K25将帮助申请者实现短期目标，并作为长期目标的垫脚石。培训计划包括与拟议的导师一对一的培训课程、实践研究、课程工作、实验室访问、出席国家和国际科学会议，以及负责任地开展研究的培训。在拨款的最初几年，申请者将学习神经解剖学、神经生物学和药物滥用方面的课程。这项建议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磁共振成像，开发急性吸烟对认知功能影响的成像生物标记物。这项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；被认为与自我监控有关的休息状态网络；以及与烟草渴望和吸烟减少相关的大脑激活模式。研究这些标志物与吸烟前、中、后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混淆的信号，这些信号严重限制了大胆的功能磁共振在一些药物滥用研究中的应用。它们允许通过近红外光谱和功能磁共振成像对不间断吸烟进行监测。通过这些实验，申请者将获得临床研究研究的所有方面的技能，并使他在人类物质滥用研究的实际问题上获得经验。这些实验将在麦克莱恩医院脑成像中心进行，该中心拥有出色的设施和工作人员，可以在药物滥用中进行复杂的近红外光谱和功能磁共振实验。综合培训和研究计划将使申请者能够将其研究从技术开发转移到生物和制药应用。拟议的有指导的培训计划将帮助申请者成为一名独立的调查员，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.