Distinct patterns of prefrontal cortical disengagement during inhibitory control in addiction: A meta-analysis based on population characteristics

Abstract

Prefrontal cortical dysfunctions underlying inhibitory control deficits in addiction are complex and likely dependent on population characteristics. Here, we conducted a meta-analysis to examine alterations in brain activations during response inhibition in addicted individuals. We characterized imaging findings based on substance use status, diagnosis, substance classes, and task performance. Results revealed in those with active drug addiction hypoactivation of the left dorsal anterior cingulate cortex (dACC) and right middle frontal gyrus (MFG), compared with healthy controls. Weakening of the dACC and MFG activations was particularly pronounced in nicotine users, respectively. Impaired task performance was also associated with diminished MFG activation. In contrast, abstinent users did not exhibit any significant differences compared with healthy controls. Those with behavioral addictions were characterized by higher midcingulate cortical activation. Thus, the neural disengagement during response inhibition in active drug addiction was limited to a small number of prefrontal cortical regions and dependent on population characteristics. Finally, the evidence for potential normalization of hypofrontality following substance use cessation highlights the benefits of abstinence in restoring cerebral functions.

Keywords: Behavioral addiction; Drug addiction; Inhibitory control deficits; Meta-analysis; Prefrontal cortex; Response inhibition; fMRI.

Figure 1:

PRISMA flow diagram. The search using Medline/PubMed, Web of Science, and Google Scholar databases identified 731 articles, 43 of which met inclusion criteria of the current meta-analysis.

Figure 2:

Alterations of neural processes underlying response inhibition in addicted individuals with active substance use, abstinent substance use, and behavioral addictions. (A) Relative to healthy controls, those with active substance use demonstrated significantly lower activation in the left dorsal anterior cingulate cortex (dACC) and right middle frontal gyrus (MFG). (B) Relative to abstinent individuals, those with active substance use exhibited significantly lower activation in the right MFG. (C) Relative to healthy controls, individuals with behavioral addictions showed greater activation in the midcingulate cortex (MCC)†. †Also significant at the more stringent voxel-level threshold of p < .05 FWE.

Figure 3:

Alterations of neural processes underlying response inhibition in individuals with active stimulant and nicotine use. (A) Relative to healthy controls, those with active stimulant use showed diminished activation in the right middle frontal gyrus (MFG) but elevated activation in the cuneus (Cu). (B) Relative to healthy controls, those with active nicotine use exhibited lower activation in the dorsal anterior cingulate cortex (dACC). (C) Group comparisons showed significantly lower right MFG but greater cuneus and dACC activation in individuals with active stimulant use relative to those with active nicotine use.

Figure 4:

Differential alterations in neural responses to inhibitory control in active substance use addicted individuals with vs. without task performance impairment. (A) Individuals with impairment demonstrated diminished activations in the right middle frontal gyrus (MFG). (B) Individuals without impairment showed reduced activation in the bilateral dorsal anterior cingulate cortex (dACC)†. (C) Group comparisons showed significantly lower right MFG but greater dACC activation in those with impaired relative to those with non-impaired performance. †Also significant at the more stringent voxel-level threshold of p < .05 FWE. ** p < .001.