The impact of theta burst stimulation over supplementary motor cortex on gait perturbations of Parkinson’s diseases patients with and without freezing of gait

Abstract

Transcranial magnetic stimulation (TMS) has the potential to modify cortical excitability as a therapy for neurological and psychiatric disease. Limitations include the transient and localised nature of the effects. In some situations, where cortical excitability is diffusely abnormal, more widespread modulation of cortical activity is desirable. The cerebellum has extensive connections to cortical areas, via the dentato-thalamo-cortical pathway, and the cerebellum is therefore a promising stimulation site for treating conditions with altered cortical excitability. Previous studies have shown that 50 Hz intermittent theta burst stimulation (iTBS) of the cerebellum increases the amplitude of motor evoked potentials (MEP) obtained from ipsilateral muscles by stimulation of the contralateral motor cortex, while continuous TBS (cTBS) has the opposite effect. In this combined TMS-electroencephalography study, the effects of 30 Hz right cerebellar hemisphere TBS on TMSevoked potentials (TEP) were investigated; in particular the effects on the N100 component, which is thought to reflect intra-cortical inhibition. 16 participants, aged 18-30 years, received 30 Hz iTBS, cTBS or sham TBS with a placebo coil in three separate sessions. MEP and TEP were recorded before and after treatment. Treatment with iTBS resulted in an increase in the amplitude of the N100 compared to sham, without significantly altering MEP amplitudes. cTBS did not significantly modify N100 amplitude and had varying effects on MEP, depending on stimulus intensity. The N100 changes were present diffusely and bilaterally. The findings suggest that 30 Hz cerebellar iTBS enhances activity in both inhibitory and facilitatory cortical networks. These effects may be useful therapeutically, but the stimulation intensity may be critical in determining the net effect on cortical excitability.