Theta Burst Stimulation of the Human Cerebellum

Abstract

Background Repetitive Transcranial Magnetic Stimulation (rTMS) of the cerebral cortex has been previously applied as a non-invasive therapy for neurological conditions due to its potential to modify cortical excitability through neuroplasticity. Cerebellar stimulation has the potential to modify cortical excitability because of its predominantly inhibitory connections with the motor cortex and other cortical areas. Previous studies have shown that cerebellar rTMS, including theta burst stimulation (TBS) can modulate excitability in the motor cortex, but the findings have been variable. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on motor evoked potentials (MEP) and TMS-evoked cortical potentials (TEP). Method Combined TMS and electroencephalography (TMS-EEG) was carried out on 16 healthy participants, aged 21-30 years. Each subject was studied in three separate sessions, in which 30Hz intermittent TBS (iTBS), continuous TBS (cTBS) or sham stimulation at stimulus intensity of 80% or 90% of active motor threshold (AMT) was applied to the right cerebellar hemisphere. Each session consisted of active and resting MEP and TEP recording from the left motor cortex before and after TBS. EEG recordings were analysed offline using EEGLAB software and independent component analysis (ICA) was used to remove artifacts. TEP were extracted and averaged. Mean N100 waveform amplitudes were measured before and after each treatment protocol. Post stimulation values for all parameters were compared using mixed model ANOVA, with pre-treatment values as covariates. Results The TBS protocol at 90% of AMT stimulus intensity produced a significant decrease in amplitude of the resting MEP after cTBS compared to sham TBS, F(2,13)= 4.87, p=0.035. Cortical silent period (CSP) was increased following iTBS, compared to sham, F(2,13)= 4.87, p=0.026. The effects of 80% TBS on MEP were not significant The mean N100 amplitude was significantly greater after iTBS than sham TBS using 80% or 90% stimulation F(2,348)=197.80, p < 0.001 and F(2,455)=6.17, p = 0.02, respectively. Conclusion The study demonstrated that 30Hz cerebellar cTBS at 90% AMT produced a reduction in overall excitability of the contralateral motor cortex, as shown by reduced resting MEP amplitude. Although iTBS produced an increase in the CSP and the N100 amplitude, both thought to reflect intracortical inhibition, there was no significant effect of iTBS on MEP amplitude. As this measure is dependent on the net effect of inhibitory and facilitatory networks in the cerebral cortex, it is possible that an increase in intracortical inhibition cancelled out the inhibitory effects. These findings provide further evidence that cortical excitability can be modulated through cerebellar TBS. Cerebellar TBS has potential as a therapeutic modality for a number of neurological conditions where there is abnormal cortical excitability, including epilepsy, dystonia and Parkinson’s disease. Future investigation of its effects is required before it can be recommended.