SWM task reaction time and accuracy data were collected during scanning and composite scores were calculated to provide a single, comprehensive measure of performance and use fewer degrees of freedom in analyses, providing more statistical power . Reaction-time data and accuracy measures were converted into z-scores, and reaction-time z-scores were subtracted from accuracy z-scores to compute the performance composite score. Using this approach, high accuracy would result in a high positive z-score, while low reaction time, which is better, would result in a high negative zscore. Therefore subtraction of the negative reaction time z-score from the positive accuracy zscore would yield a positive index indicating high overall performance Imaging Data. Imaging data from each teen were processed as in our prior studies using Analysis of Functional NeuroImages . Time series data were corrected for motion. Number of removed repetitions and average movement in each direction throughout the task were examined in relation to group, task, and interactions using correlational analyses. The average percent of repetitions removed for excessive motion during the task was 8%, resulting in 92% retained for analyses. There were no significant differences between groups in bulk motion in any of the six movement directions . The average rotational movement throughout the task for MJ users was 0.04, 0.14, and 0.05 degrees for roll, pitch, and yaw, respectively. In controls the average rotational movement throughout the task was 0.07, 0.13, and 0.06 degrees for roll, pitch, and yaw, respectively. Among MJ users, the average translational movement was 0.11, 0.05, and 0.08 mm for superior, left, and posterior, respectively; the average translational movement of controls was 0.14, 0.06, and 0.07 mm for superior, left, and posterior, respectively. There was a significant group difference in the roll direction = 2.35, p = 0.03, although such movements were quite small. Next,grow cannabis fMRI data were deconvolved with a reference function that coded the hypothesized BOLD signal for each task condition .

Controlling for linear trends, spin history effects, and delays in hemodynamic response, we computed for each brain voxel a fit coefficient that represented the relationship between the observed and hypothesized signal change for contrasts between SWM and vigilance conditions . These functional datasets were warped into standard space , resampled into 3 mm3 voxels and smoothed with a 5 mm Gaussian filter. Statistical Analyses. Regression analyses determined the variability in brain response accounted for by group, task performance, and their interaction. These group level analyses were performed in each voxel of the brain and examined the BOLD response contrast between SWM and vigilance. To control for Type I error, we only interpreted significant effects in clusters of 50 contiguous significant voxels , yielding an overall clusterwise α = .05, determined by Monte Carlo simulations . Exploratory follow-up regression analyses were performed to determine the nature of the group by performance interaction. A main effect of group revealed that marijuana users showed significantly greater activation than controls in a cluster encompassing the right basal ganglia, as well as in a second cluster encompassing the right precuneus, postcentral gyrus, and superior parietal lobule 7) and in the left precuneus and superior parietal lobule . There was no region in which marijuana users demonstrated reduced activation compared to controls . Across all subjects, both users and controls, behavioral performance data positively predicted activation in seven clusters : right middle temporal gyrus, parahippocampal gyrus, and inferior temporal gyrus; right cerebellar tonsil; right inferior parietal lobule, supramarginal gyrus, angular gyrus, and middle temporal gyrus; left middle temporal gyrus and superior temporal gyrus; left middle occipital gyrus, middle temporal gyrus, and inferior temporal gyrus; right middle frontal gyrus; and left middle frontal gyrus and inferior frontal gyrus. There were no regions in which performance was negatively associated with brain response .

A group by performance interaction was found in five clusters : left superior temporal lobule, left superior temporal gyrus and left middle temporal gyrus; right temporal gyrus and right uncus; left anterior cingulate; left uncus and left parahippocampal gyrus; and right thalamus and right pulvinar. However, findings were re-examined using movement as a covariate, and all findings remained unchanged . Performance and BOLD response data were checked for outliers, and none were found. Cases appearing as possible outliers on scatter plots were removed and analyses were redone; results remained unchanged. Both groups were checked for outliers on mood measures; although neither group contained an outlier on the BDI, the marijuana group contained one outlier on the Hamilton Anxiety Rating Scale. Analyses were re-run excluding this subject and results remained unchanged.This study examined the association between behavioral performance and brain response during a SWM task among 16- to 18-year-old marijuana users and controls after 28 days of abstinence. Results suggest that, in general, marijuana-using teens performed similarly on SWM than controls, perhaps due to the low difficulty level of the task , which approached ceiling effects. This has been observed in fMRI studies of SWM in adult marijuana users . However, specific localization and intensity of response varied between the MJ users and controls, with MJ users showing more performance-related activation in certain regions and less in others. These differential patterns emerged despite similar overall task performance across groups, suggesting an alternate relationship between task performance and brain activity among marijuana users. MJ users showed significantly more activation than controls in the right basal ganglia, an area associated with skill learning . Since the subjects were only allowed to practice the task once before entering the scanner, it is possible that the MJ users were still in the skill learning process during imaging.

The other two clusters, which were significantly more activated in marijuana users than controls, were the right and left parietal lobes. Bilateral parietal regions have been implicated in attention, spatial perception, imagery, working memory, special encoding, episodic retrieval, skill learning monitoring, organization, and planning during working memory . It is possible that there is compensatory neural effort in these areas, as observed in SWM studies of adult marijuana users . The performance data positively related to activation in several areas, and did not negatively associate with brain response in any region. Performance was positively associated with activation in the left and right temporal regions, which are associated with verbal mechanisms and episodic, nonverbal working memory and retrieval, respectively . This suggests that good task performance may be related to using multiple memory modalities. High-scorers showed more activation in the bilateral prefrontal and bilateral parietal regions that have been shown to activate during SWM tasks in youths . The performance by group interactions were the focus of this study and yielded the most interesting results. In particular,indoor cannabis grow system an interaction in the left superior temporal gyrus suggested a positive association in the users and a negative association in the controls. This may imply that the MJ users used more of a verbal strategy to achieve high task performance scores than the controls. This is interesting when considering the previous findings of deficits in verbal learning and IQ in marijuana using adolescents compared to controls . Furthermore, the right superior temporal gyrus showed an interaction where users had a negative association and controls had a positive association. Previous studies have shown this area to be involved in poorer recognition of previously seen words . This would support the notion that users are relying on a verbal strategy so that better performance linked to a decrease in activation in the right superior temporal gyrus. Moreover, an interaction in the right thalamus and pulvinar showed a negative association in the users and a positive association in the controls. These sub-cortical structures have shown an association with spatial neglect when damaged . It is interesting that these areas have a negative association in users and a positive association in controls, and may suggest that marijuana users utilize less spatial strategies than controls. The nature of the interaction revealed a positive association in marijuana users and a negative association in controls in the left anterior cingulate. This region has been linked to attention, decision-making, cue response, and response monitoring . It may be that good performing marijuana users are making a more conscious decision to react to task cues than controls, who may be reacting more automatically. The left parahippocampal gyrus demonstrated an interaction of negative association in marijuana users and positive association for controls. This region is involved in working memory and is recruited when the temporal lobe is not in use . Since marijuana users are using more energy in the left temporal lobe as their performance increases, higher scoring subjects may rely less on the parahippocampal gyrus. The distinct interactions viewed in these different areas of the brain can mean that different systems are at work, and as one part of a system decreases in action, the other area of the system increases in activation.

Previous studies suggest that subjects who do not use traditional strategies for specific tasks showed an increased extent of activation and recruitment of additional areas, specifically verbal areas, to accomplish the task . More specifically, the pattern of results suggests that marijuana users may apply a verbal strategy to the task when achieving higher scores. It is possible that this alternative way of using the brain may be less efficient; this would explain the greater overall activation in users versus controls and recruitment of other brain regions as a compensation method. A recent review also found that multiple neuroimaging studies of marijuana users pointed toward recruitment of compensatory regions as well as task-related regions to achieve task demands . A possible limitation to this study is the interpretation of a difference in fMRI activation between experimental groups. It is possible that alternative neural pathway use is more dynamic and versatile. It is unclear whether the results are an adverse effect of the marijuana use or merely a benign difference. Further studies that more carefully describe the relationships between task performance and brain response will clarify this question. Another limitation of the current study is that most marijuana users were also moderately heavy alcohol drinkers. While these participants are representative of the population of adolescent marijuana users, most of whom also consume alcohol , it is nonetheless difficult to disentangle the effects that may be related to alcohol use. Alcohol use correlated with brain response in the right thalamus and pulvinar in the current study, but results remained significant even when accounting for alcohol use, and alcohol use did not correlate to activation in any other significant regions. Our previous research identified brain response abnormalities among marijuana users above and beyond those demonstrated by users of alcohol alone , supporting the hypothesis of marijuana-specific differences in brain response, even among teens who are heavy drinkers. Future studies should attempt to clarify the differential and interactive impact of concomitant alcohol and marijuana use on brain functioning on adolescents. Furthermore, lifetime marijuana use episodes were associated with activation in the right uncus and superior temporal gyrus. Future analyses could further investigate the associations of other brain regions, as well as neuropsychological performance, with lifetime use episodes. These subtle differenced among users may provide additional insight into the mechanisms involved with prolonged abstinence from marijuana. Future studies should also focus on investigating the nature of interactions in other domains of cognition to test if other types of tasks show these patterns. If a user’s neural differences are actually a compensatory tool, then a more difficult task may overcome their compensation abilities, therefore resulting in performance deficits. In addition, a parametric manipulation of working memory load could help specify degree of compensatory activation in marijuana users compared to controls, as marijuana users may reach a limit earlier than controls. Further studies could also explore which mechanisms and strategies subjects utilize during the tasks through qualitative data investigation. Recreational marijuana commercialization is gaining momentum in the US. Among the 11 states and Washington DC that have legalized recreational marijuana since 2012, retail markets have been opened or anticipated in 10 states, where over a quarter of the US population live. The presence of recreational marijuana dispensaries increased rapidly following the commercialization. Children are at a high risk of initiating marijuana use and developing adverse consequences related to marijuana.