Sharott Andrew, Gulberti Alessandro, Zittel Simone, Tudor Jones Adam A, Fickel Ulrich, Münchau Alexander, Köppen Johannes A, Gerloff Christian, Westphal Manfred, Buhmann Carsten, Hamel Wolfgang, Engel Andreas K, Moll Christian K E
Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, United Kingdom, Department of Neurology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany, and Department of Neurosurgery, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
J Neurosci. 2014 Apr 30;34(18):6273-85. doi: 10.1523/JNEUROSCI.1803-13.2014.
Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥ 10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype.
帕金森病(PD)是一种异质性疾病,会导致多种不同运动症状的不同表现。虽然在帕金森病患者和实验动物中已观察到底丘脑核神经元的放电频率、模式和振荡变化,但将它们与特定运动症状联系起来的证据有限。在此,我们使用来自19名接受脑深部刺激手术的帕金森病患者的底丘脑核神经元细胞外记录来研究这种关系。对于每位患者,在未服药状态下记录了≥10个单神经元和/或多神经元。我们将表现出不同活动的神经元比例与术前统一帕金森病评定量表子评分(未服药)进行了关联。亚β频率下的平均频谱功率和以β频率振荡的神经元百分比分别与轴向和肢体僵硬评分呈正相关。以γ频率振荡的神经元百分比与运动迟缓评分呈负相关。平均爆发内放电频率与运动迟缓和轴向评分均呈正相关,而低于/高于10毫秒的峰间间隔相关比率与这些症状和肢体僵硬呈正相关。没有任何活动参数与震颤相关。所有显著相关的底丘脑核活动的总体平均值占运动迟缓 - 僵硬和轴向评分组合方差的>60%。我们的结果表明,基底神经节神经元速率和模式的改变可能部分是帕金森病表型变异性的基础。