Escobar Sanabria David, Johnson Luke A, Nebeck Shane D, Zhang Jianyu, Johnson Matthew D, Baker Kenneth B, Molnar Gregory F, Vitek Jerrold L
Department of Neurology, University of Minnesota, Minneapolis, Minnesota; and.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota.
J Neurophysiol. 2017 Nov 1;118(5):2654-2669. doi: 10.1152/jn.00388.2017. Epub 2017 Aug 23.
Oscillatory neural activity in different frequency bands and phase-amplitude coupling (PAC) are hypothesized to be biomarkers of Parkinson's disease (PD) that could explain dysfunction in the motor circuit and be used for closed-loop deep brain stimulation (DBS). How these putative biomarkers change from the normal to the parkinsonian state across nodes in the motor circuit and within the same subject, however, remains unknown. In this study, we characterized how parkinsonism and vigilance altered oscillatory activity and PAC within the primary motor cortex (M1), subthalamic nucleus (STN), and globus pallidus (GP) in two nonhuman primates. Static and dynamic analyses of local field potential (LFP) recordings indicate that ) after induction of parkinsonism using the neurotoxin MPTP, low-frequency power (8-30 Hz) increased in the STN and GP in both subjects, but increased in M1 in only one subject; ) high-frequency power (~330 Hz) was present in the STN in both normal subjects but absent in the parkinsonian condition; ) elevated PAC measurements emerged in the parkinsonian condition in both animals, but in different sites in each animal (M1 in one subject and GPe in the other); and ) the state of vigilance significantly impacted how oscillatory activity and PAC were expressed in the motor circuit. These results support the hypothesis that changes in low- and high-frequency oscillatory activity and PAC are features of parkinsonian pathophysiology and provide evidence that closed-loop DBS systems based on these biomarkers may require subject-specific configurations as well as adaptation to changes in vigilance. Chronically implanted electrodes were used to record neural activity across multiple nodes in the basal ganglia-thalamocortical circuit simultaneously in a nonhuman primate model of Parkinson's disease, enabling within-subject comparisons of electrophysiological biomarkers between normal and parkinsonian conditions and different vigilance states. This study improves our understanding of the role of oscillatory activity and phase-amplitude coupling in the pathophysiology of Parkinson's disease and supports the development of more effective DBS therapies based on pathophysiological biomarkers.
不同频段的振荡性神经活动以及相位-振幅耦合（PAC）被假定为帕金森病（PD）的生物标志物，它们可以解释运动回路中的功能障碍，并用于闭环深部脑刺激（DBS）。然而，这些假定的生物标志物在运动回路中的各个节点以及同一受试者体内从正常状态转变为帕金森状态时如何变化，仍然未知。在本研究中，我们描述了帕金森症和警觉性如何改变两只非人类灵长类动物初级运动皮层（M1）、丘脑底核（STN）和苍白球（GP）内的振荡活动和PAC。局部场电位（LFP）记录的静态和动态分析表明：）使用神经毒素MPTP诱导帕金森症后，两个受试者的STN和GP中的低频功率（8 - 30 Hz）增加，但只有一个受试者的M1中的低频功率增加；）两个正常受试者的STN中均存在高频功率（约330 Hz），但在帕金森状态下不存在；）两只动物在帕金森状态下均出现了升高的PAC测量值，但在每只动物的不同部位（一只受试者的M1和另一只受试者的GPe）；并且）警觉状态显著影响运动回路中振荡活动和PAC的表达方式。这些结果支持了以下假设，即低频和高频振荡活动以及PAC的变化是帕金森病病理生理学的特征，并提供了证据表明基于这些生物标志物的闭环DBS系统可能需要针对个体的配置以及适应警觉性的变化。在帕金森病的非人类灵长类动物模型中，使用长期植入的电极同时记录基底神经节-丘脑皮质回路中多个节点的神经活动，从而能够在正常和帕金森状态以及不同警觉状态之间对电生理生物标志物进行受试者内比较。本研究增进了我们对振荡活动和相位-振幅耦合在帕金森病病理生理学中的作用的理解，并支持基于病理生理学生物标志物开发更有效的DBS疗法。
