Neuroradiologic methods have shown that chronic dependent have significant reductions of brain and neuropsychological patients volume and neurobehavioral deficits. Whereas certain of these alterations reverse during abstinence, the neurocognitive deficts that persist beyond the phase of detoxification may be viewed as pre-morbid risk factors and/or determinants of treatment outcome. Our previous findings suggest the major hypothesis to be tested: Reduced absolute concentrations of the neuronal marker, N-acetylaspartate (NAA) in the cerebrellar vermis and inefficient brain activation during finger tapping both characterize disruption of fronto-cerbellar circuits in subject with poor outcome, early onset alcohol dependence and neurocognitive/affective compromise. The overall significance of the work proposed is that it will use complementary state of the art MRI and MRS measurements of brain structure, metabolism, and activation to address novel hypotheses regarding the nature of neurocognitive/affective abnormalities that either are (or are not) reversible with abstinence. We propose to determine whether impaired cerebellar and motor cortical fMRI activation during self-paced and externally paced index finger tapping with the dominant or nondominant hand and prefrontal dysfunction during performance of Simon spatial incompatibility task improve differentially over 3 months of monitored abstinence. Second, we will assess whether task performance and corresponding fMRI activation within (practice/learning effects) and between (recovery) fMRI sessions distinguish patients and controls. Third, we will study whether fMRI can identify regions in cerebellum and frontal lobes that are functionally discrepant between alcohol dependent and normal subjects to provide the focus for detailed MRS and structural MRI studies that may pinpoint the origin(s) of disruptions or corticocerebeUar circuits in alcoholics. Finally, we wish to establish the prognostic value of quantitative MR methods to predict the degree of recovery of neurocognitive/affective functions and clinical course over three months of abstinence. These investigations of pathophysiologic mechanisms underlying a alcohol-induced brain damage and recovery with abstinence are of fundamental importance, with implications for prevention, diagnosis and treatment.
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