Here, we propose that cognitive intervention and long-term abstinence attenuate cue-induced responses in the PFC, and that drug-related expectation and shortterm abstinence have the opposite effect. The impact of short-term abstinence on PFC cue-related activity has been most extensively studied in nicotine addiction (Supplementary information S4 (table)). In an arterial spin labelling MRI study, 12-hour abstinence in smokers increased craving, global CBF and regional CBF in the OFC, and decreased CBF in the right PFC, with CBF changes in all ROIs correlating with craving and withdrawal symptoms50. Such enhanced cue reactivity was also reported for longer periods of abstinence — up to 8 days in the DLPFC, ACC and inferior frontal gyrus in female smokers51 — and also positively correlated with craving52. However, some studies report no effect of abstinence on cue-induced PFC activity53. This could possibly be attributed to other factors that contribute substantial variability to results, such as the expectation to smoke at the end of the study54. Indeed, as discussed above13, expectation alone may mimic the effects of acute drug intake on PFC activation in addicted individuals.
