Neurophysiology of motor function following cannabis discontinuation in chronic cannabis smokers: an fMRI study

Abstract

The objective of this study was to identify the differences in cerebral activation between chronic cannabis smokers and controls in response to finger sequencing. We hypothesized that attentional areas related to motor function as well as primary and supplementary motor cortices would show diminished activation in chronic cannabis smokers. Nine cannabis smokers and 16 controls were included in these analyses. Scanning was performed on a GE 1.5 T scanner. Echo planar images and high-resolution MR images were acquired. The challenge paradigm included left and right finger sequencing. Group differences in cerebral activation were examined for Brodmann areas (BA) 4, 6, 24, and 32 using ROI analyses in SPM. Cannabis users, tested within 4–36 h of discontinuation, exhibited significantly less activation than controls in BA 24 and 32 bilaterally during right- and left-sided sequencing and for BA 6 in all tasks except for left-sided sequencing in the left hemisphere. There were no statistically significant differences for BA 4. None of these regional activations correlated with urinary cannabis concentration and verbal IQ for smokers. These results suggest that recently abstinent chronic cannabis smokers produce reduced activation in motor cortical areas in response to finger sequencing compared to controls.

Introduction

Several studies have documented the clinical consequences of cannabis-induced effects on motor function. Kurzthaler et al. (1999) found that perceptual motor speed and accuracy, two very important determinants of driving ability, seem to be impaired immediately after acute cannabis consumption. Many other studies (Gjerde and Kinn, 1991, Kruse and Christophersen, 1994, Soderstrom et al., 1995, Fergusson and Horwood, 2001, Hall, 2001), though not all (Levy and Jones, 2000, Wright and Terry, 2002), have reported adverse effects of acute cannabis intoxication on driving performance. Moreover, there is good consensus that cannabis produces neurophysiological deficits including deficits in attention at least during early withdrawal (Block and Ghoneim, 1993, Solowij, 1995, Fletcher et al., 1996, Pope and Yurgelun-Todd, 1996, Croft et al., 2001; Pope et al., 2001a, Pope et al., 2001b, Pope et al., 2001c, Pope et al., 2001d; Bolla et al., 2002, Solowij et al., 2002), thus raising the possibility of specific motor deficits during this period.

Barnett et al. (1985) found a significant linear correlation between tracking errors under divided attention and THC plasma levels over 25 ng/ml among cannabis users assessed approximately 2 h after smoking. Furthermore, Muller-Vahl et al. (1999) concluded that cannabinoids are of therapeutic value in the treatment of tics in Tourette syndrome, in the reduction of levodopa-induced dyskinesia in Parkinson’s disease, and in some forms of tremor and dystonia, again suggesting a role of acute cannabis intoxication in motor function.

Motor function has been shown to be subserved predominantly by primary and non-primary motor areas (Picard and Strick, 1996, Fink et al., 1997, Hammond, 2002). There is, however, growing evidence that the classical homunculus involved in finger movements may be more varied than initially thought, and that the primary motor area, supplementary motor area, and cingulate have significant variability in their connections (Takada et al., 1998, Indovina and Sanes, 2001). Although the primary motor area including the precentral gyrus has been principally identified with motor function, recent studies have shown that the SMA and the motor areas of the medial wall may also be important in understanding the functional pathways of the motor system (Fink et al., 1997). In particular, the cingulate gyrus has been identified as a key area that may be important in motor function (Takada et al., 1998, Backus et al., 2001, Akkal et al., 2002, Tanji et al., 2002). The above have been shown in numerous studies on finger sequencing (Gordon et al., 1998, Borowsky et al., 2002).

Animal studies have delineated a rostral and caudal cingulate zone, both of which have been implicated in motor function (Vogt et al., 1979, Fink et al., 1997). These animal data have led to the identification of corresponding areas of human brain suggested to be involved in movement. Hierarchically, the firing of cingulate neurons prior to the actual execution of movement suggests that it may be important in the preparatory phase of movement. Picard and Strick (1996) have demonstrated that the cingulate is important in attentional processes related to response generation. Dettmers et al. (1995) have shown that the cingulate may be important in the actual execution of movement as well, in that firing in the cingulate was found to be correlated with increasing force of movement. Moreover, numerous PET studies have demonstrated that the cingulate is important in response selection, motor learning, and motor planning (Paus et al., 1993, Thaler et al., 1995, Passingham, 1996, Grafton et al., 1998, Dagher et al., 1999).

There are only few studies on cerebral blood flow (CBF) in cannabis smokers and they address different issues than the one we are addressing. One study in chronic smokers not undergoing acute detoxification showed decreased cerebral blood flow (Lundqvist et al., 2001) while another during acute smoking showed increased frontal blood flow (Mathew and Wilson, 1993). The latter was corroborated by a study that showed increased blood flow following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in the anterior cingulate and cerebellum (O’Leary et al., 2000, O’Leary et al., 2002). One study showed lower cerebellar metabolism in chronic marijuana abusers at baseline, but increases during intoxication in the orbitofrontal cortex, prefrontal cortex and basal ganglia (Volkow et al., 1996).

We hypothesized that the cingulate would show differential patterns of activation in response to a motor task in recently abstinent chronic cannabis smokers compared to controls. We also hypothesized that chronic cannabis smokers would show lower activation of the motor cortex and supplementary motor areas during early abstinence in response to a motor task, compared to controls. To test these hypotheses, we performed functional magnetic resonance imaging on nine chronic heavy cannabis users and 16 control subjects while they performed a finger sequencing task.