This investigation had two main findings. First, our reappraisal strategy successfully suppressed cue-induced craving in smokers. Second, we found negative correlations between RCS+ induced craving and BOLD signal changes in the right dACC. Consistent with the prior research, dACC activation plays an important role in examinations of brain function during cognitive reappraisal and cognitive modulation of emotion 
Immediate reactions to emotionally evocative stimuli are not always helpful, and thus cognitive strategy is required to modify emotions toward specific goals 
. The cognitive strategy of reappraisal significantly lowered subjects’ self-reported feelings of intensity, a finding that has been reported by several studies regarding both negative 
and positive 
feelings. Our results suggested that cognitive reappraisal can be used to reduce their craving for cigarettes in smokers, which is consistent with the clinical findings that have demonstrated the efficacy of cognitive regulation in reducing craving and preventing relapse during smoking cessation 
Evidence showed that dACC play an important role in cognitive control of behavior 
. Functional imaging of Go/No-Go and Stroop interference tasks that require subjects to restrain prepotent responses consistently show recruitment of dACC 
. Activation in the dACC, which is implicated in conflict avoidance and attention control 
, may reflect the active direction of attention away from the hypersalient cigarette-related stimuli as a process that is different from automatic patterns of attention. Activity in the dACC might also be interpreted in terms of performance monitoring. One of these monitoring functions is the detection of response conflict 
. In this study, response conflict caused by the reappraisal might have arisen from two competing tendencies: top-down signals vs. bottom-up reward signals. Top-down signals reflect the intention to reappraise the cigarette cues, whereas bottom-up reward signals promote the craving for the cigarette.
As drug addiction characterized that the saliency value of a drug and its related cues are enhanced, while the inhibitory control is weakened, setting up the stage for an unrestrained cycle which leads to compulsive drug-seeking without regard to its negative consequences 
. In the present study, smokers showed increased dACC activation in the cognitive reappraisal. The result may provide a biomarker of link between cognitive control and drug cues.
Our study has numerous limitations. First, similar to many other fMRI studies, ours was limited by a small sample size. Thus, although our confidence in these results is strengthened by the identification of a priori
ROIs, these data must be considered preliminary. Future research with larger samples will be useful for increasing our confidence in this pattern of findings. Second, we restricted the sample only to males, although research has demonstrated that male and female smokers differ in their responses to smoking-related stimuli and nicotine administration 
. We sought to reduce the possibility of introducing such variance given the relatively small sample size. Whether our findings generalize to female smokers awaits direct investigation. Third, the paradigm may potentially measure craving vs
. reward expectation. Previous research suggested that manipulations that generate expectations of cigarette smoking can increase cigarette craving in smokers 
and may potentiate cue-induced cigarette craving 
. Using the same paradigm, the presentation of cues previously paired with cigarettes can elicit craving compared with stimuli that predict the absence of cigarettes in smokers 
. Fourth, the study design lacks a nonsmoking control group exposed to the same cues as the smokers. However, in prior work 
, nonsmokers demonstrated neither cigarette craving nor changes in mood/anxiety associated with the presentation of cigarette-related cues. Additionally, in our pilot study, the cigarette cue did not induce craving in nonsmoking control subjects. However, in this study, the primary analysis was the investigation of cigarette cue exposure under Regulate and Attend conditions. The use of nonsmoking control subjects would not be expected to help the central interpretation of the study.
Altered sensitivity to the incentive salience of drug cues has been proposed as the neural basis of pathological “wanting” (Volkow and Wise, 2005). The dACC, which might mediate the neural circuit involved in the craving response, provides a target for top-down cognitive interventions that may be therapeutically beneficial. This strategy may help addicted individuals avoid the anticipated situations where they are exposed to conditioned cues. Our findings suggest that smokers can use self-instruction to inhibit the craving response when they are exposed to cigarette cues. In fact, addicts are inevitably exposed to drug cues in their daily lives; therefore, the acquisition of the ability to exert cognitive control may decrease relapse rates.