Plastic responsiveness of motor cortex to paired associative stimulation depends on cerebellar input

Objective: The extent of plastic responses of motor cortex (M1) to paired associative stimulation (PAS) varies among healthy subjects. Continuous theta-burst stimulation (cTBS) of cerebellum enhances the mean PAS-induced plasticity in groups of healthy subjects. We tested whether the initial status of Responder or Non-Responder to PAS, influenced the effect of cerebellar stimulation on PAS-induced plasticity. Methods: We assessed in 19 young healthy volunteers (8 Responders, 11 Non-Responders to PAS), how cTBS and iTBS (intermittent TBS) applied to the cerebellum before a PAS protocol influenced the plastic responsiveness of M1 to PAS. We tested whether the PAS-induced plastic effects could be depotentiated by a short cTBS protocol applied to M1 shortly after PAS and whether cerebellar stimulation influenced GABA-ergic intracortical inhibition and M1 plasticity in parallel. Results: Cerebellar cTBS restored the M1 response to PAS in Non-Responders while cerebellar iTBS turned the potentiating response to PAS to a depressive response in both groups. The depotentiation protocol abolished both responses. Conclusion: Non-Responder status to PAS is a state of M1 amenable to bidirectional plastic modulation when primed by a change in cerebello-thalamic drive. Significance: The meaning of lack of responsiveness to certain protocols probing plasticity should be reconsidered. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Automated summary

The study showed that cerebellar stimulation can modulate the plastic response to PAS, and the M1 response of Non-Responders to PAS can be restored after cerebellar stimulation. This suggests that individual responses to plastic modulation may be influenced by the cerebellar neural system.