Clinical Effect on Cortical Reactivity of Theta Burst Versus High‐Frequency Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease: A TMS‐EEG Study

ABSTRACT Background Both high‐frequency repeated transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) are believed to enhance cortical excitability. However, clinical comparison of their benefits for motor improvement in Parkinson's disease (PD) as well as their underlying neurophysiological changes remain unelucidated. Objective To compare the clinical effect of rTMS versus iTBS on motor improvement and explore their influence on cortical reactivity using resting state electroencephalogram (EEG) and TMS‐EEG. Methods Idiopathic PD patients were randomized in a single‐blind, controlled trial, and received 10 sessions of either 10‐Hz rTMS or iTBS applied to the bilateral primary motor cortex (M1). Motor symptoms were evaluated using the Unified Parkinson's Disease Rating Scale. Cortical reactivity was assessed by resting state EEG and TMS‐evoked potentials. Results Included were 52 PD patients (mean [SD] age 66.2 [5.8] years). Compared to 10 Hz rTMS, iTBS was more efficient in alleviating tremor symptoms. In the iTBS group, the global mean field amplitude of P60 was significantly higher after stimulation over contralateral M1 of the affected side and was inversely correlated with motor improvement. In the 10 Hz rTMS group, the global mean field amplitude of P30 evoked by ipsilateral M1 increased significantly. The combination of oscillation and connectivity of δ frequency in the frontal cortex of PD provided a decent model in predicting iTBS responders at baseline. Conclusion Compared with high‐frequency rTMS, iTBS applied to M1 was more effective in improving tremor symptoms in PD. The two non‐invasive stimulation modalities appear to exert their effects through distinct neurophysiological pathways, as measured by EEG and TMS‐EEG.