Functional correlates of neurological soft signs in heavy cannabis users

Sensorimotor dysfunction has been previously reported in persons with cannabis dependence. Such individuals can exhibit increased levels of neurological soft signs (NSS), particularly involving motor coordination, sensorimotor integration and complex motor task performance. Abnormal NSS levels can also be detected in non-dependent individuals with heavy cannabis use (HCU), yet very little is known about the functional correlates underlying such deficits. Here, we used resting-state functional magnetic resonance imaging (MRI) to investigate associations between NSS and intrinsic neural activity (INA) in HCU (n = 21) and controls (n = 26). Compared with controls, individuals with HCU showed significantly higher NSS across all investigated subdomains. Three of these subdomains, that is, motor coordination, sensorimotor integration and complex motor task behaviour, were associated with specific use-dependent variables, particularly age of onset of cannabis use and current cannabis use. Between-group comparisons of INA revealed lower regional homogeneity (ReHo) in left precentral gyrus, left inferior occipital gyrus, right triangular pat of the inferior frontal gyrus and right precentral gyrus in HCU compared with controls. In addition, HCU showed also higher ReHo in right cerebellum and left postcentral gyrus compared with controls. Complex motor task behaviour in HCU was significantly related to INA in postcentral, inferior frontal and occipital cortices. Our findings indicate abnormal ReHo in HCU in regions associated with sensorimotor, executive control and visuomotor-integration processes. Importantly, we show associations between ReHo, cannabis-use behaviour and execution of complex motor tasks. Given convergent findings in manifest psychotic disorders, this study suggests an HCU endophenotype that may present with a cumulative risk for psychosis.

Automated summary

Sensorimotor dysfunction is observed in individuals with cannabis dependence and heavy cannabis use, as indicated by increased neurological soft signs and abnormal intrinsic neural activity. Resting-state functional MRI reveals lower regional homogeneity in certain brain regions and higher regional homogeneity in other brain regions in heavy cannabis users compared with controls. These aberrant neural activities are associated with cannabis use behavior and the execution of complex motor tasks. The study suggests a potential endophenotype in heavy cannabis users that may contribute to the risk of psychosis.