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在帕金森病中,慢性高频神经刺激撤除后,丘脑底核β振荡减弱。

Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson's disease.

作者信息

Trager Megan H, Koop Mandy Miller, Velisar Anca, Blumenfeld Zack, Nikolau Judy Syrkin, Quinn Emma J, Martin Talora, Bronte-Stewart Helen

机构信息

Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.

Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA; Stanford University Department of Neurosurgery, 300 Pasteur Drive, Stanford, CA 94305, USA.

出版信息

Neurobiol Dis. 2016 Dec;96:22-30. doi: 10.1016/j.nbd.2016.08.003. Epub 2016 Aug 21.

Abstract

Subthalamic nucleus (STN) local field potential (LFP) recordings demonstrate beta (13-30Hz) band oscillations in Parkinson's disease (PD) defined as elevations of spectral power. The amount of attenuation of beta band power on therapeutic levels of high frequency (HF) deep brain stimulation (DBS) and/or dopaminergic medication has been correlated with the degree of improvement in bradykinesia and rigidity from the therapy, which has led to the suggestion that elevated beta band power is a marker of PD motor disability. A fundamental question has not been answered: whether there is a prolonged attenuation of beta band power after withdrawal of chronic HF DBS and whether this is related to a lack of progression or even improvement in the underlying motor disability. Until now, in human PD subjects, STN LFP recordings were only attainable in the peri-operative period and after short periods of stimulation. For the first time, using an investigational, implanted sensing neurostimulator (Activa® PC+S, Medtronic, Inc.), STN LFPs and motor disability were recorded/assessed after withdrawal of chronic (6 and 12month) HF DBS in freely moving PD subjects. Beta band power was similar within 14s and 60min after stimulation was withdrawn, suggesting that "off therapy" experiments can be conducted almost immediately after stimulation is turned off. After withdrawal of 6 and 12months of STN DBS, beta band power was significantly lower (P<0.05 at 6 and 12months) and off therapy UPDRS scores were better (P<0.05 at 12months) compared to before DBS was started. The attenuation in beta band power was correlated with improvement in motor disability scores (P<0.05). These findings were supported by evidence of a gradual increase in beta band power in two unstimulated STNs after 24months and could not be explained by changes in lead impedance. This suggests that chronic HF DBS exerts long-term plasticity in the sensorimotor network, which may contribute to a lack of progression in underlying motor disability in PD.

摘要

丘脑底核(STN)局部场电位(LFP)记录显示,帕金森病(PD)患者存在β(13 - 30Hz)频段振荡,表现为频谱功率升高。高频(HF)深部脑刺激(DBS)治疗水平和/或多巴胺能药物治疗时β频段功率的衰减量,与治疗后运动迟缓及强直的改善程度相关,这提示β频段功率升高是PD运动功能障碍的一个标志。一个基本问题尚未得到解答:长期高频DBS撤除后,β频段功率是否会持续衰减,以及这是否与潜在运动功能障碍缺乏进展甚至改善有关。到目前为止,在人类PD受试者中,STN LFP记录仅能在围手术期和短期刺激后获得。首次使用一种研究性植入式传感神经刺激器(美敦力公司的Activa® PC+S),在自由活动的PD受试者中,记录/评估了慢性(6个月和12个月)高频DBS撤除后的STN LFP和运动功能障碍情况。刺激撤除后14秒内和60分钟内β频段功率相似,这表明“关治疗”实验几乎可在刺激关闭后立即进行。与开始DBS之前相比,撤除6个月和12个月的STN DBS后,β频段功率显著降低(6个月和12个月时P<0.05),且关治疗时的统一帕金森病评定量表(UPDRS)评分更好(12个月时P<0.05)。β频段功率的衰减与运动功能障碍评分的改善相关(P<0.05)。这些发现得到了如下证据的支持:24个月后,两个未受刺激的STN中β频段功率逐渐增加,且无法用导联阻抗变化来解释。这表明慢性高频DBS在感觉运动网络中发挥长期可塑性作用,这可能导致PD潜在运动功能障碍缺乏进展。

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