Prefrontal-striatal pathway underlies cognitive regulation of craving

Abstract

The ability to control craving for substances that offer immediate rewards but whose long-term consumption may pose serious risks lies at the root of substance use disorders and is critical for mental and physical health. Despite its importance, the neural systems supporting this ability remain unclear. Here, we investigated this issue using functional imaging to examine neural activity in cigarette smokers, the most prevalent substance-dependent population in the United States, as they used cognitive strategies to regulate craving for cigarettes and food. We found that the cognitive down-regulation of craving was associated with (i) activity in regions previously associated with regulating emotion in particular and cognitive control in general, including dorsomedial, dorsolateral, and ventrolateral prefrontal cortices, and (ii) decreased activity in regions previously associated with craving, including the ventral striatum, subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving correlated with decreases in ventral striatum activity and increases in dorsolateral prefrontal cortex activity, with ventral striatal activity fully mediating the relationship between lateral prefrontal cortex and reported craving. These results provide insight into the mechanisms that enable cognitive strategies to effectively regulate craving, suggesting that it involves neural dynamics parallel to those involved in regulating other emotions. In so doing, this study provides a methodological tool and conceptual foundation for studying this ability across substance using populations and developing more effective treatments for substance use disorders.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Mean craving reported by smokers as a function of cue type (cigarette/food) and instruction type (NOW/LATER). Overall, reported craving was significantly decreased on LATER vs. NOW instruction trials, across both stimulus types, and was significantly greater for cigarette compared with food cues, across both instructions. Error bars represent ±SEs. When expressed as percent drop relative to craving reported on NOW trials, regulation-related drops in craving on LATER trials were only marginally different between cigarettes and food (P < 0.07).

Fig. 2.

Regions active during or modulated by the cognitive regulation of craving. (A) Medial (Left) and lateral (Right) views of brain regions that showed greater activation in the LATER vs. NOW trials, when participants used a cognitive strategy to reduce their craving. Highlighted activations are shown in regions previously implicated in regulation of aversive emotion. (B) Medial (Left) and coronal (Right) views of brain regions that showed reduced activation in LATER vs. NOW trials. Highlighted reductions are shown in regions previously reported in studies of cue-induced craving or emotion. corr, Corrected for multiple comparisons; uncorr, uncorrected for multiple comparisons.

Fig. 3.

Mediation model for the association between dorsolateral prefrontal cortex (dlPFC), ventral striatum (VS), and regulation-related decreases in craving, whereby VS is a complete mediator of the dlPFC–craving relationship. Path coefficients are shown next to arrows indicating each link in the analysis, with SEs in parentheses. Path a refers to the path from dlPFC to VS; path b refers to the direct link between VS and craving; and path c’ refers to the total association between dlPFC and craving, without the mediator VS. *P < 0.05, **P < 0.01, ***P < 0.001.