Abstract
Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.
Highlights
Increasing evidence implicates the cerebellum both in motor control[1] and in cognitive processing[2]
Correspondence and requests for materials should be addressed to F.P. www.nature.com/scientificreports/. The anatomy of these pathways has been partially described in humans in vivo[6,7,8]; in detail, the CTC pathway has been characterized in our previous investigation[9,10], the present study focuses on reconstructing the CPC pathway
From ex vivo studies it is possible to assert that the CTC pathway originates from the cerebellum and, passing through the superior cerebellar peduncle, reaches the contralateral cerebral cortex via synapses in the contralateral ventro-anterior and ventro-lateral thalamic nuclei[3,16]; while the CPC pathway originates from the cerebral cortex and, after descending through the ipsilateral cerebral peduncle (CP), synapses in the anterior pontine nuclei (APN) and passes through the contralateral middle cerebellar peduncle (MCP) before reaching the cerebellar cortex[4,17]
Summary
Increasing evidence implicates the cerebellum both in motor control[1] and in cognitive processing[2]. The cerebellum exerts its functions in close communication with the cerebral cortex by exploiting two main pathways: the efferent cerebello-thalamo-cortical (CTC) pathway and the afferent cortico-ponto-cerebellar (CPC) pathway (Fig. 1)[3,4,5] The anatomy of these pathways has been partially described in humans in vivo[6,7,8]; in detail, the CTC pathway has been characterized in our previous investigation[9,10], the present study focuses on reconstructing the CPC pathway. The CTC and CPC pathways have been described in humans ex vivo using Nissl staining in post-mortem brains after leucotomy[21] and using confocal laser and polarized light microscopy[22] All these studies are focusing on specific aspects of the cerebro-cerebellar loop and support the knowledge that there is a complex interaction between cerebellum and cerebral cortex, involving both motor and non-motor areas. Tractography based on diffusion weighted imaging[28], despite its limitations (e.g. impossibility of detecting synapses, resolving complex tissues microstructures and inclusion of false positive results)[29,30], is currently the only method to investigate important characteristics of specific neuronal
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