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.

PUBLIC HEALTH RELEVANCE: Alcohol use disorders cause significant problems in brain functioning, physical and mental health, and productivity and pose a serious public health challenge in the U.S. Research efforts to identify brain systems supporting cognitive and motor functions that remain intact versus those that are damaged in alcoholism require innovative thinking and are a crucial step in designing treatment and rehabilitation programs. This award will provide skill expansion and mentoring to the next generation of emerging scientists as they develop their own research, targeted to identify problems, create solutions, and most importantly, translates them to clinical settings.