This revised competing renewal application builds upon our prior and ongoing investigations of affective (emotional) and conative (intention) deficits in long-term abstinent alcoholics. Neurobehavioral studies will be integrated with neuroimaging experiments developed during our recently funded supplement. We will assess alcoholism-related vulnerabilities and dysfunction in the cerebral fronto-limbic systems related to emotion, reward, and intention. We will utilize functional magnetic resonance imaging (fMRI) to probe response to affective stimuli in conjunction with electrophysiological monitoring and neurobehavioral testing. Electrodermal activity will be recorded concurrently with central hemodynamic (fMRI) changes in order to examine the coupling between autonomic and central measures during emotional activation. Structural MRI analyses will include morphometric assessment of brain structures involved in these fronto-limbic emotion and reward circuits, and diffusion tensor imaging (DTI) will be applied to assess coherence of white matter tracts connecting frontal regions with limbic, ventral striatal, and posterior cerebral systems. These experiments will probe the effects of chronic alcoholism on emotional perception, modulation, and memory. We will focus on brain structure and function underlying these neurobehavioral domains, as well as gender effects in association with alcoholism. Participants will be abstinent alcoholic men and women, ages 18-50, and nonalcoholic men and women group-matched on age, education, and IQ. We will employ behavioral, electrophysiological, and neuroimaging (DTI, structural MRI, and fMRI) techniques to examine the effects of alcoholism and gender on these fronto-limbic brain systems. The fMRI experiments will involve varying both the emotional content of the materials presented (emotional words and pictures), and the type of cognitive ability needed for task performance. Of particular focus in the imaging studies are fronto-limbic regions of interest (ROIs) tied to affective and conative functioning, regions we hypothesize to be associated with neuroanatomical, electrophysiological, and neurobehavioral deficits in alcoholism. Overall, we aim to sharpen distinctions among neurobehavioral sequelae of alcoholism in men and women, and to contribute valuable information about the neurobiology of cognitive aspects of emotion and intention deficits in alcoholism. ? ? ?
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