Our recent functional and structural magnetic resonance imaging (MRI), balance physiology, and neuropsychological studies point to cerebellar systems disruption as a principal neural mechanism underlying cognitive and motor dysfunction and processing inefficiency in chronic alcoholism. This alcoholism-induced brain pathology itself may change cognition and behavior in a manner that can perpetuate drinking. We now propose to combine sway path analysis to dissect physiological components of static balance control with high resolution structural MRI, diffusion tensor imaging (DTI), and functional MRI (fMRI) to examine the integrity of gray matter components of corticocerebellar circuits, white matter tracts linking them, and the pattern and extent of their functional activation. Our proposal aims to delineate the specific sites and neural mechanisms by which chronic alcohol use impairs cognition and balance. Recovering alcoholic men and women and age- and sex-matched controls will undergo balance testing and neuroimaging with MRI, DTI, and fMRI in a series of inter-related studies to address three specific aims: 1. Specify sources of interference that provoke postural instability in abstinent alcoholic men and women using force platform analysis. With sway path analysis, we will test whether benefits provided by a broad support base and vision to balance stabilization will be significantly reduced in alcoholics more than controls when challenged by a secondary task (mental calculation) while balancing. 2. Characterize the integrity of cerebellopontocortical circuitry with diffusion tensor imaging and cerebellar tissue with high resolution MR imaging. We will use DTI guided by fiber tracking and high resolution MR imaging to characterize the integrity of cerebellopontocortical circuitry and relate it to balance abnormality and to volumes of cerebellum and prefrontal cortex connected by these circuits. 3. Identify neural mechanisms of processing inefficiency with fMRI. We propose two fMRI experiments to identify neural systems underlying processing inefficiency in alcoholics. Our overarching hypothesis is that alcoholics can perform challenging tasks at normal levels by recruiting frontocerebellar systems in excess of those recruited by controls, and this would have the untoward outcome of reducing processing capacity available for simultaneous performance of other tasks, including maintenance of postural stability
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