Translational Studies of Brain Circuitry Disrupted by Alcoholism

描述（由申请人提供）：本K 05继续申请是对NIAAA高级科学家奖计划公告（PA-12-148）的回应，代表了NIH资助项目的综合，我是主要或指定的研究者。作为斯坦福大学医学院精神病学和行为科学系的教授，我是一名科学家，从事酗酒和衰老对大脑结构和功能影响的人类和动物转化研究。这个应用程序的主要目标是扩展我作为一个科学家的角色，一个导师谁教和领导发展中的神经科学家在我的神经科学计划的各个方面。我的研究计划使用定量行为神经科学方法，辅以结构和功能磁共振成像（MRI和fMRI），扩散张量成像（DTI）和脉冲连续动脉自旋标记（PCASL），目的是表征酒精中毒本身受影响的大脑区域，以及与发育和衰老相关的大脑变化的相互作用。我的学员将在我的研究的各个方面接受培训，重点是对具有成像背景的学员进行行为实验培训，并对具有心理学和行为背景的学员进行成像培训。我建议在该奖项的5年中每年有5名学员，每人3至5年，所有人都完成了博士后培训，现在开始成为独立的研究人员。斯坦福大学的神经科学研究社区是动态的，多方面的，互动的，吸引了最聪明的学生，研究员和教师在职业发展的各个层面。我在我自己的部门以及放射学，神经科学计划和SRI国际有重大合作。我的研究的基础是获得先进的神经成像设备和专业知识，用于我自己和我的学员的人类和动物研究。我的实验室、跨站点神经成像设施以及斯坦福大学社区的特殊正式和非正式神经科学教育计划的综合资源为我的学员提供了丰富的环境。酒精中毒的常见但常常未被认识的不良后果是认知、感觉和运动功能的微妙但功能上显著的损害。识别支持功能保持相对完整的大脑系统，以及那些在酒精中毒中受损的功能，这些功能从正常衰老或与酒精相关的偏离正常发育轨迹加重，这是设计康复工作的关键一步，以招募完整的大脑系统来补偿受损的大脑系统。让下一代学员参与并在这些领域进一步开展自己的研究，对成瘾的公共卫生问题具有显着的潜在相关性。

DESCRIPTION (provided by applicant): This K05 continuing application is in response to an NIAAA Program Announcement (PA-12-148) for a Senior Scientist Award and represents a synthesis of NIH-funded projects on which I am principal or named investigator. As a professor in the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, I am a scientist who conducts translational human and animal studies of the effects of alcoholism and aging on brain structure and function. The primary objective of this application is to extend my role as a scientist to that of a mentor who teaches and leads developing neuroscientists in all aspects of my neuroscience program. My program of research uses quantitative behavioral neuroscience approaches that are complemented with structural and functional magnetic resonance imaging (MRI and fMRI), diffusion tensor imaging (DTI), and pulse continuous arterial spin labeling (PCASL) with the aim of characterizing affected brain regions in alcoholism itself and in interaction with brain changes associated with development and senescence. My mentees will receive training in all aspects of my research with emphasis on behavioral experimental training for mentees with imaging backgrounds and training in imaging for mentees with psychology and behavioral backgrounds. I propose to have five mentees in each of the 5 years of the award, each for three to five years, all having completed postdoctoral training and now embarking on becoming independent investigators. Stanford University's neuroscience research community is dynamic, multifaceted, and interactive and attracts the brightest students, fellows, and faculty at all levels of career development. I have major collaborations in my own department as well as in Radiology, the Neuroscience Program, and SRI International. Fundamental to my research is access to advanced neuroimaging facilities and expertise for my own and my mentees' human and animal studies. The combined resources of my laboratory, across-site neuroimaging facilities, and the exceptional formal and informal neuroscience educational programs of the greater Stanford community provide a rich environment for my mentees. Common but often unrecognized untoward consequences of alcoholism are subtle but functionally significant impairments in cognitive, sensory, and motor functions. Identification of the brain systems supporting functions that remain relatively intact and those that are damaged in alcoholism with exacerbation from normal aging or subject to alcohol-related deviations from normal developmental trajectories is a crucial step in designing rehabilitation efforts for recruiting intact brain systems to compensate for damaged ones. Having the next generation of mentees engage in and then further their own research in these areas has notable potential relevance to public health concerns of addiction.