Assessing effective connectivity of the cerebellum with cerebral cortex using TMS-EEG

Background and objectives: The cerebellum provides important input to the cerebral cortex but its assessment is difficult. Cerebellar brain inhibition tested by paired-coil transcranial magnetic stimulation (TMS) is limited to the motor cortex. Here we sought to measure responses to cerebellar TMS (cbTMS) throughout the cerebral cortex using electroencephalography (EEG).Methods: Single-pulse TMS was applied with an induced upward current to the right cerebellar hemisphere in 46 healthy volunteers while recording EEG. Multiple control conditions, including TMS of right occipital cortex, cbTMS with induced downward current, and a sham condition modified specifically for cbTMS were tested to provide evidence for the specificity of the EEG responses evoked by cbTMS with an upward induced current.Results: Distinct EEG response components could be specifically attributed to cbTMS, namely a lefthemispheric prefrontal positive deflection 25 ms after cbTMS, and a subsequent left-hemispheric parietal negative deflection peaking at 45 ms. In the time-frequency-response analysis, cbTMS induced a lefthemispheric prefrontal power increase in the high-beta frequency band. These responses were not seen in the control and sham conditions.Conclusions: The EEG responses observed in this highly controlled experimental design may cautiously be attributed to reflect specific signatures of the activation of the cerebello-dentato-thalamo-cortical pathway by cbTMS. Therefore, these responses may provide biomarkers for assessing the integrity of this pathway, a proposition that will need further testing in clinical populations. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).