Translational Studies of Brain Circuitry Disrupted by Alcoholism

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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.