Kühn Andrea A, Kempf Florian, Brücke Christof, Gaynor Doyle Louise, Martinez-Torres Irene, Pogosyan Alek, Trottenberg Thomas, Kupsch Andreas, Schneider Gerd-Helge, Hariz Marwan I, Vandenberghe Wim, Nuttin Bart, Brown Peter
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London WC1N 3BG, United Kingdom.
J Neurosci. 2008 Jun 11;28(24):6165-73. doi: 10.1523/JNEUROSCI.0282-08.2008.
High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the beta (13-30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local beta activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP beta activity for 12 s after the end of stimulation and a decrease in motor cortical-STN coherence in the beta band over the same time period. The reduction in LFP beta activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of beta activity was associated with better task performance. These features were absent when power in the 5-12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological beta activity in PD.
丘脑底核高频刺激（HFS）是治疗重度帕金森病（PD）患者的一种成熟疗法，但其作用机制尚不清楚。PD患者的β（13 - 30Hz）频段振荡同步增强与运动迟缓有关。因此，我们检验了以下假设：丘脑底核高频刺激带来的临床益处伴随着局部β活动的抑制。为此，我们探究了11例PD患者在高频刺激停止后，立即从丘脑底核记录的振荡局部场电位（LFP）活动中高频刺激的后续效应。仅分析了在高频刺激停止后表现出临床益处暂时持续的患者。高频刺激结束后12秒内，丘脑底核高频刺激导致丘脑底核LFPβ活动显著降低，且在同一时期β频段运动皮层 - 丘脑底核的相干性降低。LFPβ活动的降低与简单运动任务期间的运动幅度相关，因此β活动量越小，任务表现越好。当考虑5 - 12Hz频段的功率时，这些特征并不存在。我们的研究结果表明，高频刺激可能通过调节同步振荡的病理模式发挥作用，特别是通过降低PD患者的病理性β活动。
