Mechanisms of 1 Hz Inhibitory and 5 Hz Excitatory Repetitive Transcranial Magnetic Stimulations in Parkinson's Disease: A Functional Magnetic Resonance Imaging Study

Background: Parkinson's disease (PD) is a progressive disorder with alterations in cortical functional activity. Transcranial magnetic stimulation is known to incur motor benefits in PD by inducing motor activity through cortical connectivity, although the mechanisms are unclear. Objective: The effects of repetitive transcranial magnetic stimulation (rTMS) (at three cortical sites) on functional and structural plasticity were studied in PD to understand inhibitory or excitatory rTMS-induced motor improvement. Methodology: The study was a single blind, randomized, sham-controlled type involving three groups. Three thousand rTMS pulses of frequency 1 Hz were given at primary motor area (in 13 patients of Group A) or premotor area (in Group B, n = 18) and a frequency 5 Hz at supplementary motor area in Group C (n = 19). Clinical rating scores (Unified Parkinson's Disease Rating Scale [UPDRS], Parkinson's Disease Questionaire-39 [PDQ-39]) and motor dexterity were assessed at baseline, after sham and real rTMS sessions. Visuospatial functional magnetic resonance imaging task along with T1-weighted scans (at three Tesla) were used to evaluate the motor execution and planning post rTMS intervention. Results: Improvements (p < 0.05) in UPDRS II, III, Mobility, and activities of daily living of PDQ-39, Purdue Pegboard were observed. Increased blood oxygen level-dependent (BOLD) activations (family-wise error [FWE]-corrected P-value [pFWE] <0.01) were observed in motor cortices, parietal association areas, and cerebellum in groups C and decrease in group A and B after real TMS as compared with sham. Conclusions: Repetitive TMS at motor (1 Hz) and supplementary motor (5 Hz) areas resulted in significant clinical benefits by inducing cortical plasticity. Impact statement TMS daily protocols have been commonly employed to modulate cortical connectivity in Parkinson's disease (PD). This study uses functional magnetic resonance imaging to assess rTMS-related effects in PD. Repetitive TMS protocol at higher pulses (3000/session) in primary and supplementary motor cortices administered weekly was clinically effective and safe. The results revealed functional restoration along with cortical plasticity mechanisms of externally generated movement in PD in response to noninvasive brain stimulation.