The Cerebellar Engine: Multiscale Digital Brain Co-simulations Reveal How Cerebellar Spiking Architecture Shapes Cortical Coherence

Geminiani, A.; Meier, J. M.; Perdikis, D.; Ouertani, S.; Casellato, C.; Ritter, P.; D'Angelo, E. U.

doi:10.64898/2026.04.02.715849

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bioRxiv · 10.64898/2026.04.02.715849

The Cerebellar Engine: Multiscale Digital Brain Co-simulations Reveal How Cerebellar Spiking Architecture Shapes Cortical Coherence

Geminiani, A.·Meier, J. M.·Perdikis, D.·Ouertani, S.·Casellato, C.·Ritter, P.·D'Angelo, E. U.

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Abstract

Cellular activities shape large-scale brain dynamics determining brain functioning and disease, yet the causal mechanisms across scales remain unclear. In particular, the cerebellum has been reported to modulate whole-brain dynamics during sensorimotor integration through unknown circuit interactions. To investigate the underlying mechanisms, we developed a novel multiscale digital brain simulator, in which a spiking neural network of the olivocerebellar microcircuit is embedded in a mean-field virtual mouse brain and wired using an atlas-based long-range connectome. Parameters were systematically tuned to match multiscale experimental data from primary sensory and motor cortices (S1 and M1) and cerebellum. We analyzed the role of cerebellar circuitry on sensorimotor integration by lesioning critical circuit connections in silico. Results suggested that Purkinje cell inhibition enhances the processing efficiency of the 'cerebellar engine' through decorrelation of cerebellar nuclei activity and that the pathway between mossy fibers and cerebellar nuclei is the specific pathway inside the microcircuit driving M1-S1 coherence. These results indicate a mechanistic link between cerebellar microcircuit and cortical sensorimotor processing. This novel framework opens new perspectives for the broader multiscale investigation of brain physiological and pathological states in relation to specific cellular and microcircuit properties.

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Geminiani, A., Meier, J. M., Perdikis, D., Ouertani, S., Casellato, C., Ritter, P., D'Angelo, E. U.. 2026-04-04. The Cerebellar Engine: Multiscale Digital Brain Co-simulations Reveal How Cerebellar Spiking Architecture Shapes Cortical Coherence. https://doi.org/10.64898/2026.04.02.715849

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