Novel Mechanisms Underlying Inhibitory and Facilitatory Transcranial Magnetic Stimulation Abnormalities in Parkinson's Disease

Background and Aims The motor-evoked potential (MEP) induced by transcranial magnetic stimulation (TMS), its recruitment and the conditioning effects of weak stimuli in Parkinson's disease (PD) have shown contradictory results. The aim of this study is to definitively establish the influences of PD on the TMS-evoked MEP. Methods We investigated resting and active motor thresholds, resting and active recruitment curves, and short interval intracortical inhibition (ICI) and facilitation (ICF) in 39 PD patients and 40 age-matched healthy controls. The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was used as a clinical measure. Results MEPs to single pulses were slightly, but significantly, larger in the PD patients at rest, but increased much less than controls with voluntary muscle activation. PD patients also showed clearly and consistently less ICI and ICF by the conditioning pulse. Both ICI and ICF correlated with MEP threshold in healthy subjects, but not in PD patients. None of the TMS measures correlated with the UPDRS. Conclusions This study strongly supports the view that PD-related MEPs reflect a disturbed signal-noise ratio of pyramidal neuron responses. Such disturbance may be due to a complex combination of altered presynaptic and surround inhibition that results in unbalanced excitatory/inhibitory input at the brain motor cortex level.