Fourty-four percent of twelfth-graders have used marijuana in their lifetime, 20% used in the past month, and 5% use daily , representing a large increase from the 16% of 8th graders who have tried marijuana. Furthermore, 40% of high school students who used marijuana in the past year met criteria for marijuana abuse or dependence . Marijuana use in adolescence causes significant concern since marijuana use may impact the brain, which is still developing throughout adolescence. Though overall brain size stabilizes around age five , important progressive and regressive developmental processes continue throughout adolescence, including myelination , synaptic refinement , reductions of grey matter volumes and improved cognitive and functional efficiency . It is unclear how heavy marijuana use at this time could influence neural development. The long-term effects of marijuana have not yet been determined, but could potentially have major implications on social, academic, and occupational functioning. Although a good deal of research has been done on the effects of marijuana in chronic adult users, very little is known about adolescent users. Studies have shown that chronic marijuana has an influence on the neuropsychological performance of adults within a week of use. Specifically differences have been found in attention and executive functioning , memory , psychomotor speed and manual dexterity . One study demonstrated verbal learning deficits among cannabis flood table users compared to controls 0, 1, and 7 days following use, but that these impairments subsided after a 28-day abstinence period .
However, others have identified impairments in memory, executive functioning, psychomotor speed, and manual dexterity after 28 days of verified abstinence compared to published norms . Furthermore, adults who began use early in adolescence demonstrated greater decrements on verbal IQ after a 28-day abstinence period those who began late in adolescence and non-using controls, suggesting an adolescent vulnerability . Due to its high safety profile and good spatial resolution, functional magnetic resonance imaging has become a powerful method for visualizing neural activation. Research on adult marijuana users has shown alterations in brain response via fMRI scanning. More specifically, these studies have demonstrated an increase in spatial working memory brain response in marijuana users compared to normal age-matched controls in the pre-frontal cortex, anterior cingulate, and the basal ganglia . This suggests a compensatory neural response as well as recruitment of additional brain areas to achieve necessary task requirements, as seen in a recent study of task performance and brain functioning in marijuana users . However, because this study was done on adults who were abstinent for only 6-36 hours prior to the scan, it may be that these effects reflect recent use and not persisting effects . Others have characterized visuospatial attention among 12 recent marijuana users who had used 2 – 24 hours earlier, 12 abstinent users who not used for an average of 38 months, and 19 non-using controls . Both active and abstinent users showed decreased brain response in prefrontal, parietal, and cerebellar regions that normally subserve visual attention, and increased activation in alternate regions, suggesting brain response alterations even after extended abstinence. These adult fMRI studies point to altered neural functioning among marijuana using adults during visuospatial tasks, particularly in frontal and parietal regions. Less is known about neurocognitive functioning in adolescent marijuana users. A longitudinal study of ten adolescent marijuana users showed incomplete recovery of learning and memory impairments even after six weeks of abstinence . Recent fMRI studies of SWM involving alcohol-abusing adolescents and marijuana and alcohol-abusing adolescents have found that marijuana and alcohol were associated with greater changes than alcohol alone. Specifically, after an average of 8 days of abstinence, adolescent marijuana users showed an increase in dorsolateral prefrontal activation and reduced inferior frontal response compared to alcohol users and non-using controls, suggesting compensatory working memory and attention activity associated with heavy marijuana use during youth.
Adolescent marijuana users demonstrated increased right hippo campal activity and poorer attention and verbal working memory performance compared to demographically similar tobacco smokers and non-using controls, suggesting compensatory neural recruitment, even after a month of abstinence . In a follow-up study, marijuanausing youths who were abstinent at least two weeks performed similarly as non-users on verbal working memory during ad libitum smoking and again during nicotine withdrawal, but exhibited increased parietal activation and poorer verbal delayed recall during nicotine withdrawal compared to non-marijuana users . Together, these studies suggest altered working memory functioning among adolescent marijuana users that may persist after a month of abstinence. Yet it is unclear how variability in task performance might contribute to brain activation patterns. Among normal adolescents, spatial working memory task performance is associated with activation in bilateral prefrontal and posterior parietal brain regions . Adult studies have suggested increased frontal and parietal activity associated with greater spatial working memory task difficulty . FMRI studies of adolescent and adult marijuana users have suggested that increased neural responding associated with marijuana use may be evidence of compensatory neural recruitment to maintain task performance . Therefore, the relationship between task performance and neural response may differ between marijuana users and controls, with a stronger positive relationship among marijuana users. The interaction between task performance and fMRI response to SWM has not yet been studied in adolescent marijuana users. The goal of the present study was to understand how task performance patterns contribute to neural activation in abstinent adolescent marijuana users. We studied blood oxygen level dependent fMRI neural activation during a SWM task which typically activates bilateral prefrontal and posterior parietal networks in adolescents and adults .
This SWM task has been shown to be sensitive to brain response abnormalities in adolescent alcohol and marijuana users. In this study, both adolescent users and controls were required to abstain from all drugs and alcohol for 28 days prior to their fMRI scan, and all were free from psychiatric disorders and learning disabilities. Based on our previous work we predicted that after 28 days of abstinence, marijuana users as a group would perform as well as controls; however, the task performance would vary within each group resulting in a group by task performance interaction that would be associated with brain response. Specifically, we hypothesized that there would be interactions between task performance and fMRI response in the bilateral dorsolateral prefrontal and posterior parietal cortices, such that marijuana users show a stronger positive association between performance and brain response than controls in these regions. 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 cannabis grow supplier 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, 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 subcortical 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 thecurrent 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.