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The role of sex in the association between cannabis use and working memory-related brain activity.

ABSTRACT: Although cannabis use patterns differ between men and women, studies on sex differences on the effects of cannabis on the brain and cognitive control are largely lacking. Working memory (WM) is a component of cognitive control believed to be involved in the development and maintenance of addiction. In this study, we evaluated the association between cannabis use and WM (load) related brain activity in a large sample, enabling us to assess sex effects in this association. The brain activity of 104 frequent cannabis users (63% men) and 85 controls (53% men) was recorded during an N-back WM task. Behavioral results showed a significant interaction between WM load and group for both accuracy and reaction time, with cannabis users showing a relatively larger decrease in performance with increasing WM load. Cannabis users compared to controls showed a relatively smaller reduction in WM (load) related activity in the precuneus and posterior cingulate cortex at higher WM load. This WM (load) related activity was not associated with performance nor cannabis use and related problems. An exploratory analysis showed higher WM-related activity in the superior frontal gyrus in men compared to women. While cannabis users showed higher WM (load) related activity in central nodes of the default mode network, this was not directly attributable to group specific worsening of performance under higher cognitive load. Further research is necessary to assess whether observed group differences increase with higher cognitive load, how group differences relate to measures of cannabis use, and how sex affects these group differences.

SUBMITTER: Kroon E

PROVIDER: S-EPMC9311233 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Given prior reports of adverse effects of cannabis use on working memory, an executive function with a protracted developmental course during adolescence, we examined associations between developmental patterns of cannabis use and adult working memory (WM) processes. Seventy-five adults with longitudinal assessments of cannabis use (60 with reported use, 15 with no reported use) and prenatal drug exposure assessment completed a spatial WM task during fMRI at age 28. All subjects passed a multi-drug urine screen on the day of testing and denied recreational drug use in the past week. A fast event-related design with partial trials was used to separate the BOLD response associated with encoding, maintenance, and retrieval periods of the WM task. Behavioral results showed that subjects who began using cannabis earlier in adolescence had longer reaction times (RT) than those with later initiation. Cannabis age of onset was further associated with reduced posterior parietal cortex (PPC) encoding BOLD activation, which significantly mediated age of onset WM RT associations. However, cannabis age of onset brain-behavior associations did not differ between groups with a single reported use and those with repeated use, suggesting age of onset effects may reflect substance use risk characteristics rather than a developmentally-timed cannabis exposure effect. Within repeated cannabis users, greater levels of total cannabis use were associated with performance-related increases in dorsolateral prefrontal cortex (DLPFC) activation during maintenance. This pattern of significant results remained unchanged with inclusion of demographic and prenatal measures as covariates. Surprisingly, however, at the group level, cannabis users generally performed better than participants who reported never using cannabis (faster RT, higher accuracy). We extend previous investigations by identifying that WM associations with cannabis age of onset may be primary to PPC stimulus encoding activity, while the amount of cannabis use is associated with DLPFC maintenance processes. Poorer performance of participants who reported never using cannabis and the consistency of cannabis age of onset associations across single and repeated users limit interpretation of direct developmental effects of cannabis on WM in adulthood.

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The role of sex in the association between cannabis use and working memory-related brain activity.

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