Evidence has shown that alcoholism leads to volume reductions in brain regions critical for associative learning using the eyeblink classical conditioning paradigm (EBCC). Evidence indicates that cerebellar shrinkage causes impairment in simple forms of EBCC, whereas changes in forebrain structures result in impairment in more complex tasks. In this study, the ability of abstinent alcoholics and matched control participants to acquire learned responses during delay discrimination and discrimination reversal was examined and related to severity of drinking history and neuropsychological performance. During discrimination learning, one tone (CS+) predicted the occurrence of an airpuff (unconditioned stimulus), and another tone (CS−) served as a neutral stimulus; then the significance of the tones was reversed. Alcoholics who learned the initial discrimination were impaired in acquiring the new CS+ after the tones reversed; this is a function that has previously been linked to forebrain structures. It is suggested that a factor important to alcoholic addiction may be the presence of alcoholic-related associative responses that interfere with the ability to learn new more adaptive associations. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptChronic misuse of alcohol leads to volume reductions in brain regions critical for associative learning using the eyeblink classical conditioning (EBCC) paradigm. First, alcohol is known to cause structural alterations in the cerebellum, a structure that is both necessary and sufficient for all forms of EBCC (R. F. Thompson, 1986). Such alterations have been documented by traditional postmortem inspection (Harper & Kril, 1989) and more recently by in vivo neuroimaging studies, confirming significant volume shrinkage in the cerebellar hemispheres (Sullivan, Rosenbloom, Lim, & Pfefferbaum, 2000).Second, in addition to alcohol-related neuropathological changes in the cerebellum, abundant evidence from different methodologies indicates that the structural alterations due to alcohol extend into prefrontal cortex and frontal circuitry. These are areas of the brain known to be essential for more complex or nonoptimal forms of EBCC. For example, using structural MRI, Sullivan and her colleagues (e.g., Sullivan et al., 2003; have reported that each major node of the frontocerebellar circuit shows volume reductions and each can be independently affected. MRI studies have also revealed greater volume losses in the frontal lobes compared with other structures (Dao-Castellana et al., 1998;Jernigan et al., 1991;Kril, Halliday, Svoboda, & Cartwright, 1997). White matter changes in alcoholics have been documented using diffusion tensor imaging Pfefferbaum et al., 2000). Post-mortem evidence from Harper, Kril, and Daly (1987) showed a 22% reduction in the number of neurons in the superior frontal cortex of alcoholics.Alcoholism also results in degradation of cognitive function. Neuropsychological deficits range from mild to severe (e.g., Korsakoff's syndrome) an...

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