The main limitation of this Review is our selective focus on the PFC at the expense of excluding all other cortical brain regions and subcortical structures. The architecture supporting higher-order executive function and top-down control is complex and is thought to involve several functional networks that include, in addition to the PFC, other regions such as the superior parietal cortex, insula, thalamus and cerebellum147. Consequently, and also given the inherent limitations of cross-sectional human neuroimaging studies, attribution of causality should be avoided — that is, the PFC may not directly drive the deficits described in this review. Future meta-analyses in which the disruption of these functional networks in addiction is explored should be imbued with results from mechanistic studies in laboratory animals.
