Reduced Fronto-Cerebellar Functional Connectivity in Chronic Alcoholic Patients

Background: Alcohol dependence is associated with neurocognitive deficits related to neuropathological changes in structure, metabolism, and function of the brain. Impairments of motor functioning in alcoholics have been attributed to well-characterized neuropathological brain abnormalities in cerebellum. Methods: Using functional magnetic resonance imaging (fMRI), we studied in vivo the functional connectivity between cerebellar and cortical brain regions. Participants were 10 uncomplicated chronic alcoholic patients studied after 5 to 7 days of abstinence when signs of withdrawal had abated and 10 matched healthy controls. We focused on regions of prefrontal, frontal, temporal, and parietal cortex that exhibited an fMRI response associated with nondominant hand finger tapping in the patients but not in the controls. We predicted that fronto-cerebellar functional connectivity would be diminished in alcoholics compared with controls. Results: Functional connectivity in a circuit involving premotor areas (Brodmann Area 6) and Lobule VI of the superior cerebellum was reduced in the patients compared with the controls. Functional connectivity was also reduced in a circuit involving prefrontal cortex (Brodmann Area 9) and Lobule VIII of the inferior cerebellum. Reductions in connectivity were specific to fronto-cerebellar circuits and were not found in other regions examined. Conclusions: Our findings show a pattern in recently abstinent alcoholic patients of specific deficits in functional connectivity and recruitment of additional brain regions for the performance of a simple finger-tapping task. A small sample, differences in smoking, and a brief abstinence period preclude definitive conclusions, but this pattern of diminished fronto-cerebellar functional connectivity is highly compatible with the characteristic neuropathological lesions documented in alcoholics and may reflect brain dysfunction associated with alcoholism.