50 Hz-Repetitive transcranial magnetic stimulation modulates brain connectivity in Parkinson's disease

Objectives: High-frequency repetitive transcranial magnetic stimulation (rTMS) may modulate neuronal excitability and promote the presumed “pro-kinetic” gamma frequency, while attenuating the “anti-kinetic” beta frequency. This study explores whether 50 Hz-rTMS and intermittent Theta Burst Stimulation (iTBS), of the primary motor (M1) and dorsolateral prefrontal cortex (DLPFC) enhance the gamma activity and functional connectivity within the motor circuit in Parkinson's disease (PD). Methods: We investigated pre- and post-rTMS interventional EEG in 62 PD patients following 50 Hz-rTMS and iTBS. Power spectral analysis, along with coherence and mutual information embedded in metrics of graph theory, was applied to assess the functional connectivity across the whole brain. Results: We found changes in the cluster coefficient and local efficiency of gamma activity in the left M1 following iTBS, and wider-spread changes within the sensorimotor circuit following 50 Hz-rTMS. We found no changes in the power spectrum or entrainment of the gamma activity in the motor cortex or beyond. Conclusion: The current 50 Hz-rTMS protocols modulate functional connectivity in PD patients, but not the power spectrum. These topological changes do not translate into clinical effects. These stimulation protocols may lack the specificity to be clinically effective. Significance: High frequency rTMS provides new insights in brain connectivity in the gamma bandwidth.