Two projects focusing upon the neurological, neuroradiological and cognitive consequences of long-term chronic abuse of alcohol are proposed. The first project utilizes the technology of Magnetic Resonance Imaging (MRI) to determine the localization and extent of neurologic involvement in alcoholic Korsakoff patients and detoxified alcoholics. MR images and performances on an extensive neuropsychological battery will be obtained for family history positive (FH+) and family history negative (FH-) alcoholics on two occasions separated by 12 months. The influence of a positive family history for alcoholism on brain- behavior relationships and degree of cognitive and neurologic recovery will be examined. Based upon recent neuropathological findings, it is anticipated that damage to the thalamus will be important in the behavioral deficiencies of both alcoholic populations, whereas atrophy of basal forebrain structures will be noted only in the Korsakoff patients group. The second set of studies explores the implicit memory ability of alcoholic Korsadoff and chronic alcoholic patients. Unlike our prior studies which assessed the extent of Korsakoff patients' explicit memory disorder (i.e., recall, recognition), these areas of study will now explore their preserved abilities. The areas will include word completion tasks, perceptual identification, spread of semantic activation and a new concept known as """"""""generic memory"""""""". None of these tasks require direct recall by the patient. Instead, each assesses some form of performance increment that could occur only as a consequence of prior exposure to, and implicit retention of, related material. Chronic alcoholics' performance will also be evaluated on these tasks and their scores will be compared with nondrinkers as well as Korsakoff patients. In addition, an analysis of chronic alcoholics' cognitive deficits, with an emphasis on the unique aspects of this deficit rather than upon either the continuity of deficits shared with Korsakoff patients or the parallels with the aging populace, will be undertaken. These unique areas will include """"""""automatic"""""""" implicit learning abilities and the effect of depresion on alcoholics' memory. Nondemented aged individuals perform normally on tests from these areas and alcoholic Korsakoff patients fail totally on these tasks. Consequently, deficits in performance on these tasks by chronic alcoholics could serve as discriminative contributors to their cognitive deficits.
| Pletcher, Mathew T; McClurg, Philip; Batalov, Serge et al. (2004) Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse. PLoS Biol 2:e393 |
