Altered brain activation during visuomotor integration in chronic active cannabis users: relationship to cortisol levels

Abstract

Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. Thirty cannabis users (16 men, 14 women, 18-45 years old) and 30 nondrug user controls (16 men, 14 women, 19-44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and with fMRI using a 3 Tesla scanner during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area BA 17 than cannabis users. Cannabis users also had higher salivary cortisol levels than controls (p = 0.002). Chronic active cannabis use is associated with slower and less efficient psychomotor function, especially in male users, as indicated by a shift from regions involved with automated visually guided responses to more executive or attentional control areas. The greater but altered brain activities may be mediated by the higher cortisol levels in the cannabis users, which in turn may lead to less efficient visual-motor function.

Figure 1.

Means and standard errors for the neuropsychological test performance separately for each group and sex. White bars represent the control subjects; black bars represent the cannabis users. There were significant main effects of cannabis use for both Pegboard tasks, the Trail Making A, and Rey Complex Figure (copy condition) tasks. *p < 0.05, significant difference between the two groups.

Figure 2.

Activation patterns for each group for the 2 and 4 Hz flicker frequency conditions of the visually paced finger-sequencing task (with and without cortisol as a covariate). Also presented are the correlations between superior frontal gyrus (SFG) activation and cortisol levels for all subjects. fMRI data processing was performed using FEAT (FMRI Expert Analysis Tool) Version 5.98, part of FSL (www.fmrib.ox.ac.uk/fsl). Z (Gaussianised T/F) statistic images were thresholded using clusters determined by Z > 2.0 and a (corrected) cluster significance threshold of p = 0.05. The z maps show clusters of statistical significance (p < 0.05, corrected), as determined from the FSL analysis.

Figure 3.

Differences in activation between cannabis users and control subjects for the 2 and 4 Hz flicker frequency conditions of the visually paced finger-sequencing task. Also presented is the percentage activation in the lingual and superior frontal gyri for each group for the 2 and 4 Hz condition of the visually paced finger-sequencing task. fMRI data processing was performed using FEAT Version 5.98, part of FSL. Z (Gaussianised T/F) statistic images were thresholded using clusters determined by Z > 2.0 and a (corrected) cluster significance threshold of p = 0.05. The z maps show clusters of statistical significance (p < 0.05, corrected) as determined from the FSL analysis. MFG, Middle frontal gyrus; SPL, superior parietal lobule.

Figure 4.

Differences in activation between female cannabis users and control subjects, and male cannabis users and control subjects, for the 2 and 4 Hz flicker frequency conditions of the visually paced finger-sequencing task. fMRI data processing was performed using FEAT Version 5.98, part of FSL. Z (Gaussianised T/F) statistic images were thresholded using clusters determined by Z > 2.0 and a (corrected) cluster significance threshold of p = 0.05. The z maps show clusters of statistical significance (p < 0.05, corrected) as determined from the FSL analysis. Cool (blue) colors indicate areas where cannabis users had significantly less activation than controls; hot (red/orange) colors indicate areas where cannabis users had significantly greater activation than controls.