Left Cerebellar Lesions may be Associated with an Increase in Spatial Neglect-like Symptoms.

Each cerebellar hemisphere projects to the contralateral cerebral hemisphere. Previous research suggests a lateralization of cognitive functions in the cerebellum that mirrors the cerebral cortex, with attention/visuospatial functions represented in the left cerebellar hemisphere, and language functions in the right cerebellar hemisphere. Although there is good evidence supporting the role of the right cerebellum with language functions, the evidence supporting the notion that attention and visuospatial functions are left lateralized is less clear. Given that spatial neglect is one of the most common disorders arising from right cortical damage, we reasoned that damage to the left cerebellum would result in increased spatial neglect-like symptoms, without necessarily leading to an official diagnosis of spatial neglect. To examine this disconnection hypothesis, we analyzed neglect screening data (line bisection, cancellation, figure copying) from 20 patients with isolated unilateral cerebellar stroke. Results indicated that left cerebellar patients (n = 9) missed significantly more targets on the left side of cancellation tasks compared to a normative sample. No significant effects were observed for right cerebellar patients (n = 11). A lesion overlap analysis indicated that Crus II (78% overlap), and lobules VII and IX (66% overlap) were the regions most commonly damaged in left cerebellar patients. Our results are consistent with the notion that the left cerebellum may be important for attention and visuospatial functions. Given the poor prognosis typically associated with neglect, we suggest that screening for neglect symptoms, and visuospatial deficits more generally, may be important for tailoring rehabilitative efforts to help maximize recovery in cerebellar patients.

Cannabinoid type-2 receptors modulate terpene induced anxiety-reduction in zebrafish.

Terpenes are the most extensive and varied group of naturally occurring compounds mostly found in plants, including cannabis, and have an array of potential therapeutic benefits for pathological conditions. The endocannabinoid system can potently modulate anxiety in humans, rodents, and zebrafish. The 'entourage effect' suggests terpenes may target cannabinoid CB1 and CB2 receptors, among others, but this requires further investigation. In this study we first tested for anxiety-altering effects of the predominant 'Super-Class' terpenes, bisabolol (0.001%, 0.0015%, and 0.002%) and terpinolene (TPL; 0.01%, 0.05%, and 0.1%), in zebrafish with the open field test. Bisabolol did not have an effect on zebrafish behaviour or locomotion. However, TPL caused a significant increase in time spent in the inner zone and decrease in time spent in the outer zone of the arena indicating an anxiolytic (anxiety decreasing) effect. Next, we assessed whether CB1 and CB2 receptor antagonists, rimonabant and AM630 (6-Iodopravadoline) respectively, could eliminate or reduce the anxiolytic effects of TPL (0.1%) and ß-caryophyllene (BCP; 4%), another super-class terpene previously shown to be anxiolytic in zebrafish. Rimonabant and AM630 were administered prior to terpene exposure and compared to controls and fish exposed to only the terpenes. AM630, but not rimonabant, eliminated the anxiolytic effects of both BCP and TPL. AM630 modulated locomotion on its own, which was potentiated by terpenes. These findings suggest the behavioural effects of TPL and BCP on zebrafish anxiety-like behaviour are mediated by a selective preference for CB2 receptor sites. Furthermore, the CB2 pathways mediating the anxiolytic response are likely different from those altering locomotion.

Examining behavioural test sensitivity and locomotor proxies of anxiety-like behaviour in zebrafish.

This study assessed the sensitivity of four anxiety-like behaviour paradigms in zebrafish: the novel tank dive test, shoaling test, light/dark test, and the less common shoal with novel object test. A second goal was to measure the extent to which the main effect measures are related to locomotor behaviours to determine whether swimming velocity and freezing (immobility) are indicative of anxiety-like behaviour. Using the well-established anxiolytic, chlordiazepoxide, we found the novel tank dive to be most sensitive followed by the shoaling test. The light/dark test and shoaling plus novel object test were the least sensitive. A principal component analysis and a correlational analysis also showed the locomotor variables, velocity and immobility, did not predict the anxiety-like behaviours across all behaviour tests.