In a response inhibition study by Casey et al. , it was found that the volume of activation in the middle frontal gyrus is correlated with age, suggesting that this structure may be important in the developmental improvement of inhibitory abilities. Furthermore, several studies support that the development of the response inhibition circuitry continues to develop well into late adolescence. Given that the OPPS sample is comprised of young adults who on average have been smoking marijuana for 4.5 years , it is possible that their exposure to marijuana over those years may have compromised middle frontal gyrus development and thus, explain the dose dependent increase in activation. These results emphasize the importance of early education about the potential cognitive impact of early exposure to marijuana.Another brain region that showed a significant positive relationship between activation and amount of marijuana smoked was the right thalamus. The thalamus is included in various circuits including the frontal-striatal-thalamic and the cingulo-opercular networks.

The frontal-striatal-thalamic circuit has been found to support the development of inhibitory control and correlate with better performance on inhibitory tasks.The cinguloopercular network, which also includes the thalamus,among other brain regions, is thought to support response rate. Response rate refers to the ability to apply cognitive skills in a consistent and flexible manner depending on atask’s demands . A voxel-based morphometry study revealed that marijuana users had increased gray matter density in the right precentral gyrus and right thalamus compared to nonusers . The authors speculated that changes in one component of the brain, gray matter in this case, may be compensated for by changes in a neighbouring component, for example, gray matter displacement caused by a decrease of nearby white matter. Therefore,it is possible that the greater activation found in the right thalamus of marijuana users in the present study may be related to a change in white matter in other areas forming part of the inhibitory pathways. Consequently, compensation on such circuits may have occurred by increased activation of the right thalamus in order for users to keep up with the behavioral demands of the “Press for all except X” condition.

The inability to assess white and gray matter volumes in the present study is a limitation and future research is required.The present study also revealed a trend for a positive relationship between amount of marijuana smoked and greater bilateral activation in the inferior parietal lobe.More specifically,right parietal regions have been implicated in sustained attention , with neuroimaging studies reporting parietal activation during attentionally demanding tasks to be in the superior, rather than inferior, parietal lobule . Together, these results suggest that marijuana users may recruit additional parietal regions in order to properly sustain their attention during response inhibition tasks.Additionally, the parietal lobes are also part of the frontal-parietal circuit, which has also been associated with inhibitory control and working memory . This network has been found to continue to reorganize through adolescence, becoming more distinct and segregated from one another and further integrating long distance connections . As previously mentioned, the OPPS sample of users had been smoking marijuana since adolescence. Therefore, it is possible that the relationship between neural activation and marijuana consumption may be due to either a delay or to an altered development of such a network due to marijuana exposure during years where response inhibition circuits are still under development.

Another positively related trend from the present study was observed in the precuneus. This region is thought to have a role in error awareness and monitoring ,which is an important aspect of prefrontal cortex function since error detection allows for the correction and improvement of task performance . Support for this evidence is found in electrophysiological and lesion studies that propose that this region may be involved inevaluative functions such as monitoring behaviour . Moreover, Nagahama et al.have found that the precuneus is activated when external feedback shifts from “correct” to “incorrect” during tasks where subjects are required to alter stimulus-response judgments. Although during the Go/No-Go task, in the present study did not introduce an error awareness task, these findings may indicate that marijuana users need to work harder in order to monitor their response and be aware of errors during their performance. However, further testing with a response inhibition task that includes error awareness recognition should be carried out in order to confirm this result.Although other fMRI studies researching response inhibition in marijuana users have found greater activation in prefrontal regions including the dorsolateral prefrontal cortex , the present study provides further evidence that other brain regions of response inhibition circuitry may also be altered.