Cerebellar control over inter-regional excitatory/inhibitory dynamics discriminates execution from observation of an action

Lorenzi, R. M.; Korkmaz, G.; Alahmadi, A. A. S.; Monteverdi, A.; Casiraghi, L.; D'Angelo, E.; Palesi, F.; Gandini Wheeler-Kingshott, C. A. M.

doi:10.1101/2024.05.21.595114

bioRxiv · 10.1101/2024.05.21.595114

Cerebellar control over inter-regional excitatory/inhibitory dynamics discriminates execution from observation of an action

Lorenzi, R. M.·Korkmaz, G.·Alahmadi, A. A. S.·Monteverdi, A.·Casiraghi, L.·D'Angelo, E.·Palesi, F.·Gandini Wheeler-Kingshott, C. A. M.

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Abstract

The motor learning theory anticipates that cerebro-cerebellar loops perform sensorimotor prediction thereby regulating motor control. This operation has been identified during action execution (AE) and observation (AO) but the causal interaction between the cerebellum and cerebral cortex remained unclear. Here we used Dynamic Causal Modelling (DCM) to study functional MRI (fMRI) data obtained during a squeeze ball task in either the AE or AO conditions. In both cases, active regions included bilateral primary visual cortex (V1), left primary motor cortex (M1), left supplementary motor and premotor cortex (SMAPMC), left cingulate cortex (CC), left superior parietal lobule (SPL), and right cerebellum (CRBL). AE and AO networks showed the same fixed effective connectivity, with pathways between V1, CRBL, SMAPMC and CC wired in a closed loop. However, the cerebellar communication towards the cerebral cortex switched from excitatory in AE to inhibitory in AO. Moreover, in AE only, signal modulation was non-linear from SMAPMC to CRBL and within the CRBL self-connection, supporting the role of the CRBL in elaborating motor plans received from SMAPMC. Thus, the need for motor planning and the presence of a sensorimotor feedback in AE discriminate the modality of forward control operated by the CRBL on SMAPMC. While the underlying circuit mechanisms remain to be determined, these results reveal that the CRBL differentially controls the excitatory/inhibitory dynamics of inter-regional effective connectivity depending on its functional engagement, opening new prospective for the design of artificial sensorimotor controllers and for the investigation of neurological diseases.

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Lorenzi, R. M., Korkmaz, G., Alahmadi, A. A. S., Monteverdi, A., Casiraghi, L., D'Angelo, E., Palesi, F., Gandini Wheeler-Kingshott, C. A. M.. 2024-05-21. Cerebellar control over inter-regional excitatory/inhibitory dynamics discriminates execution from observation of an action. https://doi.org/10.1101/2024.05.21.595114

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