Translational Studies of Brain Circuitry Disrupted by Alcoholism

描述(由申请人提供)：此K05申请是对NIAAA计划公告(PA-06-555)的高级科学家奖的回应，并代表了我作为首席研究员的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教授，我有两个主要角色：1)作为科学家，我对酒精中毒和衰老对大脑结构和功能的影响进行人类和动物的翻译研究；2)作为导师，我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。环境：斯坦福大学的神经科学研究社区是动态的、多方面的，吸引着各个职业发展水平的最聪明的学生。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，供我自己和我的导师进行人类和动物研究。我的实验室的资源、神经成像设施，以及斯坦福社区特殊的正式和非正式的神经科学教育项目，为我的学员提供了一个丰富的环境。 研究。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)和质子磁共振波谱(MRS)，目的是描述酒精中毒本身的大脑受影响区域，以及与衰老相关的大脑变化的相互作用。除了人体研究，我的研究还包括过度酒精暴露的动物模型。我的研究计划的最终目标是确定那些受酒精中毒影响的功能和结构神经系统是永久性的，以及那些可以幸免或可以修复的。 关联性。我的研究结果对公共卫生具有显著的潜在相关性。酒精中毒的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显著的功能障碍。例如，我们的工作揭示了与年龄和酒精中毒有关的姿势控制机制的妥协，这些机制可以通过补充感觉运动输入来改善，但如果放任不管，可能会导致摔倒。识别支持认知、感觉和运动功能的相对完整的大脑系统，以及那些在酒精中毒中因衰老而恶化而受损的大脑系统，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。

DESCRIPTION (provided by applicant): This K05 application is in response to an NIAAA Program Announcement (PA-06-555) for a Senior Scientist Award and represents a synthesis of NIH-funded projects on which I am principal investigator. As a professor in the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, I have two principal roles: 1) as a scientist, I conduct human and animal, translational studies of the effects of alcoholism and aging on brain structure and function; 2) as a mentor, I teach and lead developing neuroscientists in all aspects of my neuroscience program. Environment: Stanford University's neuroscience research community is dynamic, multifaceted, and attracts the brightest students 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 mentees1 human and animal studies. The combined resources of my laboratory, the neuroimaging facilities, and the exceptional formal and informal neuroscience educational programs of the greater Stanford community provide a rich environment for my mentees. Research. 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 proton MR spectroscopy (MRS) with the aim of characterizing affected brain regions in alcoholism itself and in interaction with brain changes associated with senescence. In addition to human investigations, my research entails animal models of excessive alcohol exposure. The ultimate goal of my program of research is to identify those functional and structural neural systems affected by alcoholism that are permanent and those that are spared or restorable. Relevance. The outcome of my studies has notable potential relevance to public health. Common, but often unrecognized, untoward consequences of alcoholism are subtle but functionally significant impairments in cognitive, sensory, and motor functions. Our work, for example, has revealed age- and alcoholism-related compromise of postural control mechanisms that could be ameliorated by supplementary sensorimotor input, but if left unattended to could lead to falling. Identification of the brain systems supporting cognitive, sensory, and motor functions that remain relatively intact and those that are damaged in alcoholism with exacerbation from aging is a crucial step in designing rehabilitation efforts for recruiting intact brain systems to compensate for damaged ones.