by Keyword: Cerebellum

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Blithikioti, C., Miquel, L., Batalla, A., Rubio, B., Maffei, G., Herreros, I., Gual, A., Verschure, P., Balcells-Oliveró, M., (2019). Cerebellar alterations in cannabis users: A systematic review Addiction Biology 24, (6), 1121-1137

Cannabis is the most used illicit substance in the world. As many countries are moving towards decriminalization, it is crucial to determine whether and how cannabis use affects human brain and behavior. The role of the cerebellum in cognition, emotion, learning, and addiction is increasingly recognized. Because of its high density in CB1 receptors, it is expected to be highly affected by cannabis use. The aim of this systematic review is to investigate how cannabis use affects cerebellar structure and function, as well as cerebellar-dependent behavioral tasks. Three databases were searched for peer-reviewed literature published until March 2018. We included studies that focused on cannabis effects on cerebellar structure, function, or cerebellar-dependent behavioral tasks. A total of 348 unique records were screened, and 40 studies were included in the qualitative synthesis. The most consistent findings include (1) increases in cerebellar gray matter volume after chronic cannabis use, (2) alteration of cerebellar resting state activity after acute or chronic use, and (3) deficits in memory, decision making, and associative learning. Age of onset and higher exposure to cannabis use were frequently associated with increased cannabis-induced alterations. Chronic cannabis use is associated with alterations in cerebellar structure and function, as well as with deficits in behavioral paradigms that involve the cerebellum (eg, eyeblink conditioning, memory, and decision making). Future studies should consider tobacco as confounding factor and use standardized methods for assessing cannabis use. Paradigms exploring the functional activity of the cerebellum may prove useful as monitoring tools of cannabis-induced impairment.

Keywords: Behavior, Cannabis use, Cerebellum, Cognitive function, Structure

Herreros, Ivan, Miquel, Laia, Blithikioti, Chrysanthi, Nuño, Laura, Rubio Ballester, Belen, Grechuta, Klaudia, Gual, Antoni, Balcells-Oliveró, Mercè, Verschure, P., (2019). Motor adaptation impairment in chronic cannabis users assessed by a visuomotor rotation task Journal of Clinical Medicine 8, (7), 1049

Background—The cerebellum has been recently suggested as an important player in the addiction brain circuit. Cannabis is one of the most used drugs worldwide, and its long-term effects on the central nervous system are not fully understood. No valid clinical evaluations of cannabis impact on the brain are available today. The cerebellum is expected to be one of the brain structures that are highly affected by prolonged exposure to cannabis, due to its high density in endocannabinoid receptors. We aim to use a motor adaptation paradigm to indirectly assess cerebellar function in chronic cannabis users (CCUs). Methods—We used a visuomotor rotation (VMR) task that probes a putatively-cerebellar implicit motor adaptation process together with the learning and execution of an explicit aiming rule. We conducted a case-control study, recruiting 18 CCUs and 18 age-matched healthy controls. Our main measure was the angular aiming error. Results—Our results show that CCUs have impaired implicit motor adaptation, as they showed a smaller rate of adaptation compared with healthy controls (drift rate: 19.3 +/− 6.8° vs. 27.4 +/− 11.6°; t(26) = −2.1, p = 0.048, Cohen’s d = −0.8, 95% CI = (−1.7, −0.15)). Conclusions—We suggest that a visuomotor rotation task might be the first step towards developing a useful tool for the detection of alterations in implicit learning among cannabis users.

Keywords: Cerebellum, Cannabis, Implicit motor learning, Motor adaptation, Visuomotor rotation

Amil, A. F., Maffei, G., Puigbò, J. Y., Arsiwalla, X. D., Verschure, P., (2019). Robust postural stabilization with a biomimetic hierarchical control architecture Biomimetic and Biohybrid Systems 8th International Conference, Living Machines 2019 (Lecture Notes in Computer Science) , Springer, Cham (Nara, Japan) 11556, 321-324

Fast online corrections during anticipatory movements are a signature of robustness in biological motor control. In this regard, a previous study suggested that anticipatory postural control can be recast as a sensory-sensory predictive process, where hierarchically connected cerebellar microcircuits reflect the causal sequence of events preceding a postural disturbance. Hence, error monitoring signals from higher sensory layers inform lower layers about violations of expectations, affording fast corrections when the normal sequence is broken. Here we generalize this insight and prove that the proposed hierarchical control architecture can deal with different types of alterations in the causal structure of the environment, therefore extending the limits of performance.

Keywords: Anticipatory control, Cerebellum, Control architecture, Robustness

Maffei, Giovanni, Herreros, Ivan, Sanchez-Fibla, Marti, Friston, Karl J., Verschure, Paul F. M. J., (2017). The perceptual shaping of anticipatory actions Proceedings of the Royal Society B , 284, (1869)

Humans display anticipatory motor responses to minimize the adverse effects of predictable perturbations. A widely accepted explanation for this behavior relies on the notion of an inverse model that, learning from motor errors, anticipates corrective responses. Here, we propose and validate the alternative hypothesis that anticipatory control can be realized through a cascade of purely sensory predictions that drive the motor system, reflecting the causal sequence of the perceptual events preceding the error. We compare both hypotheses in a simulated anticipatory postural adjustment task. We observe that adaptation in the sensory domain, but not in the motor one, supports the robust and generalizable anticipatory control characteristic of biological systems. Our proposal unites the neurobiology of the cerebellum with the theory of active inference and provides a concrete implementation of its core tenets with great relevance both to our understanding of biological control systems and, possibly, to their emulation in complex artefacts.

Keywords: Active inference, Cerebellum, Computational model, Motor control, Perceptual learning

Tomas-Roig, J., Piscitelli, F., Gil, V., del Río, J. A., Moore, T. P., Agbemenyah, H., Salinas-Riester, G., Pommerenke, C., Lorenzen, S., Beißbarth, T., Hoyer-Fender, S., Di Marzo, V., Havemann-Reinecke, U., (2016). Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice Behavioural Brain Research , 303, 34-43

Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.

Keywords: Psychosocial stress, Cerebellum, Calreticulin, Endocannabinoid system, Behavior, RNA seq.