Effects of acute nicotine on brain function in healthy smokers and non-smokers:estimation of inter-individual response heterogeneity

This study used fMRI to investigate the neural mechanisms of nicotine effects on antisaccades (a measure of the conflict between a reflexive response and an incompatible complex volitional response). We also aimed to identify variables with significant inter-individual heterogeneity in response to nicotine. To do so we calculated within-session intraclass correlation (ICC) coefficients over measurements obtained before and after nicotine/placebo administration and reasoned that a significant reduction in ICC with nicotine compared to placebo would reflect the operation of inter-individual response heterogeneity. 13 smokers and 11 non-smokers completed fMRI before and after subcutaneous injection of 12µg/kg nicotine or placebo in a double-blind, randomised, cross-over design. Nicotine significantly reduced antisaccade latencies in both groups. BOLD response in the left frontal eye field was non-significantly reduced by nicotine while it significantly increased following placebo in non-smokers, but there was no discernible effect in smokers. ICC analysis identified significant inter-individual response heterogeneity in antisaccade reflexive errors in smokers, and in a number of brain regions, particularly in non-smokers. These findings suggest that nicotine has beneficial effects at the cognitive level and leads to reductions in task-related activations. ICC analysis confirmed that nicotine effects are subject to inter-individual variability at behavioural and neural levels.