Seeking a unified framework for cerebellar function and dysfunction: From circuit operations to cognition

IRCCS C. Mondino, Brain Connectivity Center Pavia, Italy.
Frontiers in Neural Circuits (Impact Factor: 3.6). 11/2012; 6:116. DOI: 10.3389/fncir.2012.00116
Source: PubMed


Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive, and emotional functions (at least partially) segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis): from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the "timing and learning machine" capabilities long attributed to the cerebellum), which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia, and depression.

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Available from: Stefano Casali
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    • "These studies clearly implicate the cerebellum in decision - making processes . Although the cerebellum has been linked to the modulation of cognitive and emotional behaviors , based on its large anatomical and functional connections through the dentate nuclei with the prefrontal , temporo - parietal , and limbic areas ( Schmahmann , 2010 ; D ' Angelo and Casali , 2013 ) , whether the cerebellum functions in integrating the emotional and cognitive components during decision - making has not been examined and could be of interest in order to clarify its role in pathologies such as schizophrenia , autism and alexithymia . "
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    • "Additionally, the cerebellum is involved in higher cognitive functions (Schmahmann, 2001; Andreasen and Pierson, 2008). The cerebellar circuits process learning (particularly errorrelated ), timing and prediction in relation to motor and cognitive information (D3Angelo and Casali, 2012). The timing hypothesis postulates that the cerebellum is critical for representing temporal relationships among task-relevant events, which is closely related to the concept of synchrony. "
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    • "We considered the left and right cerebellar tracts separately because many functional imaging studies observe lateralized activity in the right cerebellum during reading [Marien et al., 2001; Price, 2012] and because dyslexia has been associated with abnormal lateralization of the cerebellar gray matter volume [Rae et al., 2002]. We did not anticipate substantial associations between FA within the ICP and reading measures, given anatomical and physiological evidence that the ICP conveys mostly sensorimotor information to the cerebellum via spinocerebellar and olivocerebellar connections [D'Angelo and Casali, 2013; Naidich et al., 2009]. "
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