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Question Voluntary movement control and execution are regulated by the influence of the cerebellar output over different interconnected cortical areas, through dentato-thalamo connections. However, in humans, connectivity and plasticity dynamics of the cerebellar-thalamo-cortical connections have been only indirectly explored. Methods In the present study we applied in a group of healthy volunteers transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to directly assess the effects of three theta-burst stimulation (TBS) protocols (intermittent, continuous and sham) over the primary motor cortex (M1) and the posterior parietal cortex (PPC) of the contralateral hemisphere. Results We found a TBS-dependent bidirectional modulation over TMS-evoked activity; specifically, cTBS increased whereas iTBS decreased activity between 100 and 200 ms after TMS, in a similar manner over both M1 and PPC areas. On the oscillatory domain, TBS induced specific changes over M1 natural frequencies of oscillation: TMS-evoked alpha activity was decreased by cTBS whereas beta activity was enhanced by iTBS. No effects were observed after sham stimulation. Conclusions Our data provide novel evidence showing that the cerebellum exerts its control on the cortex likely by impinging on specific set of interneurons dependent on GABA-ergic activity. We show that cerebellar TBS modulates cortical excitability of distant interconnected cortical areas by acting through common temporal, spatial and frequency domains. Download : Download high-res image (481KB) Download : Download full-size image Download : Download high-res image (558KB) Download : Download full-size image

Question Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective therapy in Parkinson’s disease (PD). The effects of STN-DBS on cortical reactivity are still poorly understood. By combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG), we explored the effects of STN-DBS either alone or in combination with levodopa (LD), on cortical activity evoked by TMS of the primary motor cortex (M1) in a sample of PD patients chronically treated with STN implantation. Methods Six advanced PD patients treated with STN-DBS were tested in three clinical conditions on distinct days: (i) on therapy/on DBS; (ii) off therapy/on DBS; (iii) off therapy/off DBS. In each condition, 80 single TMS pulses were delivered over left M1 while simultaneously acquiring EEG. We evaluated TMS-induced changes in the time domain and in the time/frequency domain. Results In the OFF/ON condition there was a significant increase of GMFP peaking at 60–70 ms (P2) compared to OFF/OFF condition. In ON/ON condition a significant increase of GMFP peaking at 60–70 ms (P2) and at 100 ms (P3) was observed compared to OFF/OFF condition. Time/frequency analysis showed a synchronization of activity in the 10–17 Hz range over central-posterior region within the P2 time window in the OFF/ON condition compared to OFF/OFF. The same analysis conducted on the P3 time window revealed a synchronization of activity in the 11–16 Hz range of frequency over central regions when comparing OFF/ON condition to ON/ON. Conclusions Our data reveal that bilateral STN-DBS induces a significant modulation of cortical global reactivity at early components. The association of LD therapy produces additional distinct modulation of later components. These findings could be related to cortical induced modulation of GABAergic intracortical activity.