Neural Substrates Underlying Eyeblink Classical Conditioning in Adults With Alcohol Use Disorders.

Abstract

Excessive alcohol consumption produces changes in the brain that often lead to cognitive impairments. One fundamental form of learning, eyeblink classical conditioning (EBC), has been widely used to study the neurobiology of learning and memory. Participants with alcohol use disorders (AUD) have consistently shown a behavioral deficit in EBC. The present functional magnetic resonance imaging (fMRI) study is the first to examine brain function during conditioning in abstinent AUD participants and healthy participants. AUD participants met DSM-IV criteria for alcohol dependence, had at least a 10-year history of heavy drinking, and were abstinent from alcohol for at least 30days. During fMRI, participants received auditory tones that predicted the occurrence of corneal airpuffs. Anticipatory eyeblink responses to these tones were monitored during the experiment to assess learning-related changes. Behavioral results indicate that AUD participants showed significant conditioning deficits and that their history of lifetime drinks corresponded to these deficits. Despite this learning impairment, AUD participants showed hyperactivation in several key cerebellar structures (including lobule VI) during conditioning. For all participants, history of lifetime drinks corresponded with their lobule VI activity. These findings suggest that excessive alcohol consumption is associated with abnormal cerebellar hyperactivation and conditioning impairments.