Reorganization of frontal systems used by alcoholics for spatial working memory: an fMRI study

Chronic alcoholism is associated with impairment in sustained attention and visual working memory. Thus, alcoholics have reduced ability, but not necessarily inability, to perform these executive tasks, assumed to be subserved by regions of prefrontal cortex. To identify neural substrates associated with this impairment, we used functional MRI (fMRI) to determine whether alcoholics invoke the same or different brain systems as controls when engaged in working memory tasks that the two groups were able to perform at equivalent levels. The fMRI spatial working memory paradigm instructed subjects to respond with a button press when a target position was either in the center of the field (match to center) or matched the spatial position of one presented two items previously (match 2-back) or to rest. Using whole-brain fMRI, alcoholics showed diminished activation frontal cortical systems compared to controls (bilateral dorsolateral prefrontal cortex) when responding 2-back vs rest. In the center vs rest contrast, the control group compared with the alcoholic group activated a large expanse of prefrontal cortex (including Brodmann areas 9, 10, and 45), whereas there was significantly greater activation by the alcoholic group relative to the control group localized more posteriorly and inferiorly in the frontal cortex (area 47). Examination of within group activation patterns revealed two different patterns of activation: the control group exhibited activation of the dorsal ("Where?") stream for visual spatial working memory processing, whereas the alcoholic group exhibited activation of the ventral ("What?") stream and declarative memory systems to accomplish the spatial working memory task. The differences in the pattern of brain activations exhibited by the alcoholic and control groups, despite equivalence in behavioral performance, is consistent with a functional reorganization of the brain systems invoked by alcoholic individuals or invocation of an inappropriate brain system when engaged in a visual spatial task requiring working memory.