The Cerebellar Engine: Multiscale Digital Brain Co-simulations Reveal How Cerebellar Spiking Architecture Shapes Cortical Coherence
Journal:
bioRxiv
Published Date:
Jun 24, 2026
Abstract
The impact of cellular activities on large-scale brain dynamics is thought to determine brain functioning and disease, yet the causal relationships of neural mechanisms across scales remain unclear. Recently, the cerebellum has been reported to affect whole-brain dynamics during sensorimotor integration. To disclose the underlying mechanisms, we developed a novel multiscale digital brain co-simulator, in which a spiking neural network of the olivo-cerebellar microcircuit is embedded in a virtual mouse brain and wired with other nodes using an atlas-based long-range connectome. Parameters and bi-directional interfaces between the spiking olivo-cerebellar network and other rate-coded modules were tuned to match experimental data of primary sensory and motor cortex (M1 and S1) power spectral densities and neuronal cerebellar spiking rates. Then, the role of the cerebellar circuitry on sensorimotor integration was analyzed by lesioning critical circuit connections in silico. Simulations identified the specific pathway inside the microcircuit driving M1-S1 coherence, and the role of Purkinje cell inhibition in enhancing the processing efficiency of the cerebellar engine through decorrelation of cerebellar nuclei activity. These results provide a mechanistic explanation of how the cerebellum promotes the formation of sensorimotor contingencies in cortical modules setting the basis for its predictive capability. This novel modelling approach opens new perspectives for the multiscale investigation of brain physiological and pathological states in relation to specific cellular and microcircuit properties.
