Molina Rene, Hass Chris J, Sowalsky Kristen, Schmitt Abigail C, Opri Enrico, Roper Jaime A, Martinez-Ramirez Daniel, Hess Christopher W, Foote Kelly D, Okun Michael S, Gunduz Aysegul
Department of Electrical and Computer Engineering, University of Florida, Gainesville, FL, United States.
Norman Fixel Institute for Neurological Diseases and the Program for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States.
Front Hum Neurosci. 2020 Jun 4;14:194. doi: 10.3389/fnhum.2020.00194. eCollection 2020.
This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson's disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off- and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1-8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD. Clinicaltrials.gov identifier; NCT02318927.
本研究旨在描述帕金森病（PD）队列中人脑脚桥核（PPN）区域和苍白球内侧部（GPi）步态的神经生理学相关性。尽管通过动物研究对PPN区域已有很多了解，但来自行走中的人类的生理记录有限。PPN最近作为改善PD患者步态和步态冻结（FoG）的潜在深部脑刺激（DBS）靶点而受到关注。我们使用双向神经刺激器，在一小群尽管使用了优化的多巴胺能药物但仍有FoG的重度PD受试者中，记录人脑PPN区域和GPi的情况。5名确诊为多巴胺能药物治疗下仍有FoG的受试者植入了双侧GPi和双侧PPN区域DBS电极。术后5个月，在非用药和用药状态下（在无刺激状态下获得）的各种步态任务中进行电生理记录。结果显示，GPi中低β功率受到抑制，PPN区域存在1-8Hz调制，且与人类步态相关。PPN特征与步行速度相关。随着受试者从休息状态进入行走任务，观察到GPi的β去同步化和PPN的低频同步化。我们的研究结果增进了我们对支撑步态的神经生理学的理解，并可能有助于开发针对PD异常步态的新疗法。Clinicaltrials.gov标识符：NCT02318927。
