A deficit in attention associated with abrupt cessation of smoking contributes to the difficulty of smoking cessation. The neural basis of the deficit associated with acute smoking abstinence is not well understood. The frontoparietal attentional network mediates attention and exerts top-down attentional control over the activation of sensory cortex, including the fusiform face area. We posit that abrupt cessation of cigarette smoking impairs the functional efficiency of this network, and that acute nicotine administration at least partially alleviates this impairment. To test this hypothesis, we developed a selective attention task with four levels of attention/perception load. It uses schematic images efface as target and distracters. Paired with functional magnetic resonance imaging (fMRI), our task will allow us to assess the relations between attention/perception load and task- related changes of fMRI signal in the frontoparietal cortex and the fusiform face area. We will study 20 smokers, and use load-dependent activity in the frontoparietal cortex as an indication of attentional control, and load-dependent activity in the fusiform face area as an index of the effectiveness of attentional control. Each subject will be studied in three fMRI sessions (different days), one after smoking ad libitum + placebo, the other after abstinence (12 h) + placebo, and the remaining one after abstinence (12 h) + nicotine (4 mg). We predict that, relative to activation after smoking ad libitum + placebo, smokers after abstinence + placebo will show higher activation in the frontoparietal cortex and similar activation in the fusiform face area at low attention/perception load, and less increase in activation in these brain regions as task load is increased. We also predict that, relative to activation after abstinence + placebo, smokers after abstinence + nicotine will show higher activation in the frontoparietal cortex and similar activation in the fusiform face area at low task load, and greater increases in activation in these brain areas as task load is increased. The findings from the proposed research will clarify how the function of the frontoparietal attentional network of smokers is affected by abrupt cessation of smoking and by nicotine administration, and will also provide a tool for assessing how attention is affected by the interaction of smoking cessation with other factors, such as gender and genotype. By elucidating the neural substrates of impairments in withdrawal- associated deficits in attention, this work can help identify treatment targets and possibly new approches to therapy for nicotine dependence. ? ? ?
