Cognitive Changes Associated with Chronic Alcohol Abuse

Harvard University (Medical School), Boston MA

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Abstract

ESCRIPTION (provided by applicant): The primary aim of this proposal is to evaluate the ability of abstinent chronic alcoholics to acquire, express and retain conditioned responses during complex classical eyeblink associative learning tasks. We have conducted several investigations of associative learning using relatively simple eyeblink classical conditioning tasks with abstaining alcoholics in prior studies and propose to expand this line of investigation using more challenging and informative eyeblink associative learning tasks. In our past investigations, we have found impairments in the learning and timing of conditioned responses that we attributed to cerebellar atrophy that is typical following chronic misuse of alcohol. However, it is in fact unclear to what extent their deficits are attributable solely to cerebellar atrophy because the neural circuit that supports various forms of eyeblink classical conditioning involves additional regions of the forebrain such as the hippocampal system and frontal cortex, and these regions are also impacted by the effects of alcohol. We further propose to relate these findings to underlying neuropathology (as indexed by MRI) and neuropsychological function. Of particular interest will be to relate eyeblink conditioning performance to underlying white matter using diffusion tensor imaging to examine whether possible changes in neural connectivity are related to impaired learning. We will also investigate whether possible deficits in alcoholics' ability to become explicitly aware of stimulus contingencies contributes to their impairment. The proposed investigation, using classical eyeblink conditioning tasks that are well understood at the level of neural networks in nonhuman animals, will help us to further define the extent of associative learning impairment in alcoholics and begin to uncover the human neuropathology that is responsible for impaired and preserved learning. Gaining a comprehensive understanding of the underlying nature of the proposed learning deficit in the formation of new associative memories may be critical to understanding why the behavioral changes needed to control abusive drinking may be particularly difficult for these individuals.