Wagner Jonas R, Schaper Miriam, Hamel Wolfgang, Westphal Manfred, Gerloff Christian, Engel Andreas K, Moll Christian K E, Gulberti Alessandro, Pötter-Nerger Monika
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Hum Neurosci. 2022 Feb 28;16:812954. doi: 10.3389/fnhum.2022.812954. eCollection 2022.
Freezing of gait (FoG) is a disabling burden for Parkinson's disease (PD) patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra (STN+SN DBS) moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear.
Twelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication in a standardized stepping in place paradigm. Patients executed the task with DBS switched off (STIM OFF), conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes.
Clinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta (4-8 Hz), alpha (9-13 Hz), and high-beta (21-30 Hz) band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas.
STN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD.
冻结步态（FoG）是帕金森病（PD）患者的一项致残负担，对传统疗法反应不佳。丘脑底核和黑质联合深部脑刺激（STN+SN DBS）作为治疗帕金森步态障碍和难治性FoG的一种潜在治疗选择而受到关注。DBS在皮质-皮质下-基底神经节网络中对步态的作用机制，尤其是在皮质水平，仍不清楚。
12例特发性PD患者和长期植入DBS电极，在标准化原地踏步范式下接受常规多巴胺能药物治疗评估。患者在DBS关闭（刺激关闭）、传统STN DBS和联合STN+SN DBS状态下执行任务，并与健康匹配对照组进行比较。在静息状态、有效踏步和冻结发作期间同时记录高密度脑电图和运动学测量。
临床上，与传统STN DBS相比，STN+SN DBS在改善患侧腿的时间步幅变异性方面更具优势。在静息状态和有效踏步期间，与健康对照组相比，刺激关闭状态下PD患者的皮质活动在θ（4-8Hz）、α（9-13Hz）和高β（21-30Hz）频段表现为过度同步。与刺激关闭相比，两种主动DBS设置均同样降低了静息状态下的α功率，并减少了静息状态和有效踏步期间病理性增强的高β活动。与有效踏步相比，STN DBS和STN+SN DBS期间的冻结发作表现出频谱和空间上不同的皮质活动模式。在STN DBS期间，FoG与中央皮质区域皮质α和低β活动增加有关，而在STN+SN DBS期间，高β活动在更靠前的区域增加更为明显。
与传统STN DBS相比，STN+SN DBS改善了帕金森步态障碍的时间方面，并在正常运动和冻结期间对皮质振荡模式产生不同影响，提示其对PD中功能失调的皮质-皮质下通信具有潜在调节作用。
