Regulation of Craving: Neural Correlates and the Role of Stress and Delay Discounting.

Regulation of craving (ROC) by focusing on long-term negative consequences of drug use has been shown to successfully reduce subjective craving. This process is supported by the dorsolateral prefrontal cortex (dlPFC), which exerts control over reward and value signals in the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC). As stress impairs cognitive control and addiction is characterized by altered value computations manifesting in delay discounting, we examined how these factors interact with ROC and its neural correlates to better understand the use of ROC in high-risk situations. Sixty-eight male smokers underwent a delay discounting task and either a stress (socially evaluated cold pressor task) or a control condition. They subsequently completed a ROC task during fMRI while focusing on (1) long-term negative consequences (LATER) versus (2) short-term positive consequences (NOW). We found lower subjective craving ratings and attenuated neural responses in the VS (t = 4.33, p = 0.012) and vmPFC (t = 5.79, p < 0.001), as well as higher activation in the dlPFC (t = 4.09, p = 0.038) in the LATER compared to the NOW strategy. Although no neural or behavioural difference in ROC was observed between stress and control groups, both individual stress (cortisol) and delay discounting were positively related to vmPFC activity (NOW > LATER). We replicated previous results on ROC. Importantly, the association of vmPFC signals with stress response and delay discounting suggests that enhancing ROC success may involve reinforcing changes in self-referentiality of future thoughts to subjective value of drug use.