Objective:The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers.Method: Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. Results:In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. Conclusions:In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smokingrelated images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions. Cues related to addictive drugs are well known to induce craving and drug use in addicts. The sight of a bare forearm may prompt a heroin user to inject, while the sight and smell of a burning cigarette will elicit a strong urge to smoke in an abstinent smoker (1, 2). However, despite extensive behavioral and physiological work on cue effects, relatively few studies have explored the effects of drug cues on human brain activity.Several imaging studies have examined the effects of drug-related stimuli on brain activation in substance users. Two positron emission tomography studies used visual stimuli (a cocaine video and a neutral-content video) to detect brain regions in cocaine addicts activated by drug craving (3, 4). One study found significant activation in the amygdala, anterior cingulate, and temporal pole, while the other detected significant activation in the dorsolateral prefrontal, medial orbitofrontal, temporal, retrosplenial, visual, and temporal/parietal cortices. Likewise, functional magnetic resonance imaging (fMRI) studies have detected significant activation of the anterior cingulate (5-7) and activation (5, 6) or deactivation (7) of the prefrontal cortex by cocaine videos. Many brain regions activated by a cocaine video were also activated by a sex video in both cocaine-using and comparison subjects, suggesting a common neural circuit that responds to emotionally evocative stimuli (5)....

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