Cortical Disinhibition Drives Freezing of Gait in Parkinson's Disease and an Exploratory Repetitive Transcranial Magnetic Stimulation Study

作者：Huimin Sun, Caiting Gan, Lina Wang, Min Ji, Xingyue Cao, Yongsheng Yuan, Heng Zhang, Aidi Shan, Mengxi Gao, Kezhong Zhang · 发表于：Movement Disorders · 年份：2023 · DOI：10.1002/mds.29595 · 被引用次数：16 · 研究领域：Transcranial Magnetic Stimulation Studies、Balance, Gait, and Falls Prevention、Muscle activation and electromyography studies

BACKGROUND: Dysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD). OBJECTIVE: The aim was to reveal the mechanisms of "OFF-period" FOG (OFF-FOG) and "levodopa-unresponsive" FOG (ONOFF-FOG) in PD. METHODS: We measured the transcranial magnetic stimulation (TMS) indicators and gait parameters in 21 healthy controls (HCs), 15 PD patients with ONOFF-FOG, 15 PD patients with OFF-FOG, and 15 PD patients without FOG (Non-FOG) in "ON" and "OFF" medication conditions. Difference of TMS indicators in the four groups and two conditions and its correlations with gait parameters were explored. Additionally, we explored the effect of 10 Hz repetitive TMS on gait and TMS indicators in ONOFF-FOG patients. RESULTS: In "OFF" condition, short interval intracortical inhibition (SICI) exhibited remarkable attenuation in FOG patients (both ONOFF-FOG and OFF-FOG) compared to Non-FOG patients and HCs. The weakening of SICI correlated with impaired gait characteristics in FOG. However, in "ON" condition, SICI in ONOFF-FOG patients reduced compared to OFF-FOG patients. Pharmacological treatment significantly improved SICI and gait in OFF-FOG patients, and high-frequency repetitive TMS distinctly improved gait in ONOFF-FOG patients, accompanied by enhanced SICI. CONCLUSIONS: Motor cortex disinhibition, represented by decreased SICI, is related to FOG in PD. Refractory freezing in ONOFF-FOG patients c...