Abstract
RATIONALE: Beyond the amelioration of deprivation-induced impairments, and in contrast to effects on attentional processes, the cognitive-enhancing properties of nicotine on working memory (WM) operations remain unclear. OBJECTIVES: In an effort to elucidate potential enhancing effects, we explored the impact of transdermal nicotine on neural functioning in minimally deprived smokers and, in addition, assessed differences between smokers and non-smokers using a mixed block/event-related fMRI design that attempted to isolate specific central executive operations (attentional switch events) within general WM function (task blocks). METHODS: In task blocks, participants performed a continuous counting paradigm that required the simultaneous maintenance of, and frequent switching of attentional focus between, two running tallies in WM on some trials. Cigarette smokers (n = 30) were scanned twice, once each with a nicotine and placebo patch, while non-smokers (n = 27) were scanned twice with no patch. RESULTS: Across both groups, task blocks were associated with bilateral activation, notably in medial and lateral prefrontal cortex (PFC), anterior insula, and parietal regions, whereas individual attentional switch trials were associated with activation in a similar, but predominantly left-lateralized network. Within the smoker group, although nicotine increased heart rate, altered performance and mood, and reduced tobacco cravings, no acute drug (state-like) effect on brain activity was detected for either the task or switch effects. However, relative to non-smokers, smokers showed greater tonic activation in medial superior frontal cortex, right anterior insula, and bilateral anterior PFC throughout task blocks (trait-like effect). CONCLUSIONS: These data suggest smokers require recruitment of additional WM and supervisory control operations during task performance.