Cannabis-Using Youth Demonstrated Blunted Rostral Anterior Cingulate Cortex Activation, but Normal Functional Connectivity, During an Emotional Go/No-Go Task

Abstract

Cannabis use has been associated with deficits in self-regulation, including inhibitory control. Cannabis users have previously exhibited both structural and functional deficits in the rostral anterior cingulate cortex (rACC), a region involved in self-regulation of emotional response and inhibitory control. The present study aimed to examine whether abstinent cannabis users demonstrated abnormal functional activation and connectivity of the bilateral rACC during an emotional inhibitory processing task, and whether gender moderated these relationships. The study also aimed to examine whether bilateral rACC activation and connectivity in cannabis users was related to perceived stress. It was hypothesized that cannabis users would exhibit hypoactivation and hyperconnectivity of the rACC with the rest of the brain during emotional inhibitory processing. Further, it was predicted that female cannabis users would exhibit the most pronounced activation and connectivity abnormalities. It was also expected that abnormal functional activation and connectivity would be related to increased perceived stress. In the current study, cannabis users ages 16-25 underwent fMRI scanning while completing a Go/No-go task using fearful and calm emotional faces as non-targets. Participants were excluded for psychiatric disorders, major medical conditions, and excessive other drug use. Multiple linear regression and ANCOVA were used to determine (1) if cannabis group status was related to rACC activation and functional connectivity after controlling for alcohol and nicotine use and (2) whether gender moderated these relationships. Functional connectivity analysis included linear modeling consistent with psychophysiological interaction (PPI) analysis. Subsequently, Pearson correlations were conducted to investigate whether significant activation and functional connectivity were associated with perceived stress. Results showed blunted bilateral rACC activation in cannabis users during fearful response inhibition. Male, relative to female, cannabis users had greater right rACC connectivity with the right cerebellum during calm response inhibition (marginal finding; cannabis x gender interaction did not reach significance). Further, across the entire sample, males, relative to females, had enhanced right rACC and precuneus/posterior cingulate connectivity during calm response inhibition, which was related to gender differences in perceived stress. These results suggest that chronic cannabis use may disrupt typical rACC development, conferring risk for later development of mood disorders.