Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation

Abstract

Attention and memory deficits have been reported in heavy marijuana users, but these effects may be reversible after prolonged abstinence. It remains unclear whether the reversibility of these cognitive deficits indicates that chronic marijuana use does not alter cortical networks, or that such changes occur but the brain adapts to the drug-induced changes. Blood oxygenation-level dependent (BOLD) functional MRI (fMRI) was performed in 24 chronic marijuana users (12 abstinent and 12 active) and 19 age-, sex- and education-matched control subjects during a set of visual-attention tasks with graded levels of difficulty. Neuropsychological tests were also administered on each subject. The two marijuana user groups showed no significant difference in usage pattern (frequency or duration of use, age of first use, cumulative joints used, averaged >2000 joints) or estimated cumulative lifetime exposure of Delta-9-tetrahydrocannabinol (THC) (mean 168 +/- 45 versus 244 +/- 135 g). Despite similar task and cognitive test performance compared with control subjects, active and abstinent marijuana users showed decreased activation in the right prefrontal, medial and dorsal parietal, and medial cerebellar regions, but greater activation in various frontal, parietal and occipital brain regions during the visual-attention tasks (all with P < or = 0.001, corrected, cluster level). However, the BOLD signals in the right frontal and medial cerebellar regions normalized with duration of abstinence in the abstinent users. Active marijuana users, with positive urine tests for THC, showed greater activation in the frontal and medial cerebellar regions than abstinent marijuana users and greater usage of the reserve network (regions with load effect), suggesting a neuroadaptive state. Both earlier age of first use and greater estimated cumulative dose of THC exposure were related to lower BOLD signals in the right prefrontal region and medial cerebellum. The altered BOLD activation pattern in the attention network and hypoactivation of the cerebellum suggest neuroadaptive processes or alteration of brain development in chronic marijuana users. These changes also may be related to marijuana-induced alteration in resting cerebral blood volume/flow or downregulation of cannabinoid (CB1) receptors. The greater activation in the active compared with abstinent marijuana users demonstrates a neuroadaptive state in the setting of active marijuana use, while the long-term chronic effect of marijuana on the altered brain network may be reversible with prolonged abstinence.

Abstinent adolescent marijuana users show altered fMRI response during spatial working memory

“…Thus, abstinent MJ teens may rely more on spatial rehearsal and attention rather than general executive abilities to perform the task, resulting in increased recruitment of posterior parietal cortex, but decreased right dorsolateral prefrontal activity. This altered pattern is consistent with previous evidence of reorganized attentional networks in MJ users (Chang et al, 2006). Further, estimates of typical blood-alcohol concentration achieved were negatively associated with parietal response among MJ teens, which could indicate that heavier drinking MJ teens may demonstrate less neural compensation or be less likely to utilize spatial strategies relative to those with lighter alcohol use histories.…”

“…However, after 25 days of abstinence, adult marijuana users showed decreased left dorsolateral prefrontal blood flow during a modified Stroop task (Eldreth et al, 2004). Moreover, during visual attention, active marijuana users with positive urine toxicology screens evidenced greater reductions in right prefrontal fMRI response than abstinent users (Chang et al, 2006). Considered together with the results of the current study, these findings suggest a change in neural recruitment throughout the course of abstinence.…”

“…Heightened activation among individuals with substance use disorders may be associated with compensatory neural responding to perform well on a task (e.g., Kanayama et al, 2004;Tapert et al, 2004;Schweinsburg et al, 2005b;Chang et al, 2006;Jacobsen et al, 2007). MJ teens in the current study displayed increased response in parietal cortex, yet diminished activation in prefrontal cortex, both of which play important roles in SWM (Wager and Smith, 2003).…”

“…Such occipital hyperactivation among MJ teens was not observed during SWM blocks, during which attentional resources were not focused solely on visual selective attention, but allocated to accommodate working memory processing. Previous studies have implicated diminished attentional capacity in heavy marijuana-using adults (Solowij et al, 1991(Solowij et al, , 1995Chang et al, 2006) and adolescents (Tapert et al, 2002;Schweinsburg et al, 2005b). During SWM, MJ teens may allocate limited attentional resources to spatial processing, depriving attentional input to executive systems, resulting in increased parietal and decreased frontal activation.…”

“…However, after 28 days of abstinence, current users performed similarly to former users and controls on all tests, suggesting that neurocognitive decrements may resolve within a month of abstinence (Pope et al, 2001). Importantly, fMRI evidence indicates that both abstinent users and active users show brain response abnormalities relative to controls during visual attention (Chang et al, 2006), suggesting lasting changes in patterns of neural activity. Together, these studies indicate that neuropsychological decrements observed after 1 week of use may not persist, and highlight the importance of examining neural responding after several weeks of abstinence.…”