Differences in "bottom-up" and "top-down" neural activity in current and former cigarette smokers: Evidence for neural substrates which may promote nicotine abstinence through increased cognitive control.

Drug-related stimuli, through conditioning, are thought to acquire incentive motivational properties that code possible reward availability and elicit an attentional bias, possibly through increased "bottom-up" neural processing. The processes underlying this attentional bias are considered important in the maintenance of addiction, and crucially, in relapse among substance users attempting to remain abstinent. Equally, impaired "top-down" cognitive control may impair the ability to restrain "bottom-up" pre-potent behaviours, such as drug use, following exposure to drug-related stimuli. Two experiments sought to identify the neural loci of bottom-up/top-down processing during fMRI. Experiment 1 utilised an attentional bias paradigm to examine the behavioural and neural responses to neutral, emotionally evocative and smoking-related cues in control (n=13), ex-smoking (n=10 - abstinent >12months) and smoking (n=13 - mean >6.5years of use) groups. Experiment 2 used a go/no-go paradigm to examine the neural correlates of motor response inhibition and error monitoring in the same sample. The results of Experiment 1 demonstrated that, across conditions, current smokers had significantly less neural activity in cortical but significantly more activity in subcortical areas compared to both controls and ex-smokers. Ex-smokers exhibited more neural activity than both control and smoker groups in prefrontal cortical regions. Similarly, Experiment 2 revealed that smokers had reduced neural activity in prefrontal cortical regions during motor response inhibition compared to controls while ex-smokers demonstrated greater neural activity in prefrontal cortical regions compared to both controls and smokers during error monitoring. The results reveal cortical and subcortical differences between current smokers and controls and a general pattern of increased prefrontal cortical activity in ex-smokers. These findings may suggest that elevated topdown control might be an important characteristic of successful abstinence in individuals formerly dependent on nicotine.