Laird Cermak - US grants

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.

This program proposal seeks support for a Memory Disorders Research Center which is dedicated to the study of the information- processing deficits underlying memory disturbances of individuals suffering brain injury or disease. These investigations will utilize contemporary research techniques and instrumentation to explore the on-line processing impairments of amnesic patients. This will permit greater understanding of the memory process and will provide a basis for differential assessment and therapy. Toward this end, four independent, yet interrelated projects are proposed. The first (Issues) focuses on unresolved issues of amnesia including an analysis of the relative contributions of episodic and semantic memory to implicit priming; compilation and organizational aspects of procedural learning; reconstruction and familiarity as aspects of contextual learning and, finally, factors underlying remote memory disturbances. The second component (Case Studies) seeks to describe unique individual cases of amnesia both from a clinical and issue-driven experimental point of view. Alcoholic Korsakoff, post-encephalitic, anoxic, bilateral temporal, retrosplenial and selective stroke patients will be assessed for their dissociative memorial abilities and disabilities. The third component (Neuroanatomy) explores the neuroanatomy of amnesia using neuro-imaging techniques such as MRI and CAT scans. This will culminate in a greater understanding of the neural systems underlying memory and information processing. The fourth component (Assessment and Therapy) will develop an assessment battery to permit the differential diagnosis of amnesic patients along many of the dimensions explored in the Issues Component of this proposal. This assessment will then provide a basis for therapeutic attempts with some of these amnesic individuals. The entire Center will be administered, organized and monitored through the development of a Core administration depicted in the fifth, and final component of this program project. This will include administrative assistance, secretarial support, consults and educational opportunities. The entire program will thus bring together research from otherwise diverse, and often disparate, areas of investigation to explore the behavioral, cognitive and neural underpinnings of amnesia.