Translational Studies of Brain Circuitry Disrupted by Alcoholism

描述(由申请人提供)：本K05继续申请是对NIAAA计划公告(PA-12-148)的高级科学家奖的回应，并代表了我是负责人或被任命为调查员的NIH资助项目的综合。作为斯坦福大学医学院精神病学和行为科学系的一名教授，我是一名科学家，负责对酗酒和衰老对大脑结构和功能的影响进行人类和动物翻译研究。这个应用程序的主要目标是将我作为科学家的角色扩展到导师的角色，在我的神经科学项目的各个方面教授和领导发展中的神经科学家。我的研究项目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)，目的是描述酒精中毒本身的受影响大脑区域，以及与与发育和衰老相关的大脑变化的相互作用。我的受训者将接受我研究的所有方面的培训，重点是为具有成像背景的受训者提供行为实验培训，并为具有心理学和行为背景的受训者进行成像培训。我建议在该奖项的5年中每年有5名导师，每人为期3至5年，所有人都完成了博士后培训，现在开始成为独立调查人员。斯坦福大学的神经科学研究社区是动态的、多方面的和互动的，吸引了各个职业发展水平的最聪明的学生、研究员和教职员工。我在自己的部门以及放射学、神经科学项目和SRI国际都有重要的合作。我的研究的基础是能够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。我的实验室的资源、跨地点的神经成像设施，以及大斯坦福社区特殊的正式和非正式的神经科学教育计划，为我的学员提供了一个丰富的环境。酒精中毒常见但往往未被认识到的不良后果是认知、感觉和运动功能的微小但功能显著的损害。识别那些支持功能相对完整的大脑系统，以及那些在酒精中毒中因正常衰老而恶化或受到与酒精相关的偏离正常发育轨迹的大脑系统受损的大脑系统，是设计康复努力的关键一步，以招募完整的大脑系统来补偿受损的大脑系统。让下一代被辅导者从事并进一步开展他们自己在这些领域的研究，与公众对成瘾的潜在担忧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.