Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455.
J Neurosci. 2021 Mar 10;41(10):2274-2286. doi: 10.1523/JNEUROSCI.1591-20.2021. Epub 2021 Jan 22.
Elevated synchronized oscillatory activity in the beta band has been hypothesized to be a pathophysiological marker of Parkinson's disease (PD). Recent studies have suggested that parkinsonism is closely associated with increased amplitude and duration of beta burst activity in the subthalamic nucleus (STN). How beta burst dynamics are altered from the normal to parkinsonian state across the basal ganglia-thalamocortical (BGTC) motor network, however, remains unclear. In this study, we simultaneously recorded local field potential activity from the STN, internal segment of the globus pallidus (GPi), and primary motor cortex (M1) in three female rhesus macaques, and characterized how beta burst activity changed as the animals transitioned from normal to progressively more severe parkinsonian states. Parkinsonism was associated with an increased incidence of beta bursts with longer duration and higher amplitude in the low beta band (8-20 Hz) in both the STN and GPi, but not in M1. We observed greater concurrence of beta burst activity, however, across all recording sites (M1, STN, and GPi) in PD. The simultaneous presence of low beta burst activity across multiple nodes of the BGTC network that increased with severity of PD motor signs provides compelling evidence in support of the hypothesis that low beta synchronized oscillations play a significant role in the underlying pathophysiology of PD. Given its immersion throughout the motor circuit, we hypothesize that this elevated beta-band activity interferes with spatial-temporal processing of information flow in the BGTC network that contributes to the impairment of motor function in PD. This study fills a knowledge gap regarding the change in temporal dynamics and coupling of beta burst activity across the basal ganglia-thalamocortical (BGTC) network during the evolution from normal to progressively more severe parkinsonian states. We observed that changes in beta oscillatory activity occur throughout BGTC and that increasing severity of parkinsonism was associated with a higher incidence of longer duration, higher amplitude low beta bursts in the basal ganglia, and increased concurrence of beta bursts across the subthalamic nucleus, globus pallidus, and motor cortex. These data provide new insights into the potential role of changes in the temporal dynamics of low beta activity within the BGTC network in the pathogenesis of Parkinson's disease.
β 频段同步振荡活动升高被假设为帕金森病 (PD) 的一种病理生理学标志物。最近的研究表明，帕金森病与丘脑底核 (STN) 中β 爆发活动的振幅和持续时间增加密切相关。然而，β 爆发动力学如何从正常状态到帕金森状态在基底节-丘脑皮质 (BGTC) 运动网络中改变尚不清楚。在这项研究中，我们在三只雌性恒河猴中同时记录了 STN、苍白球内节 (GPi) 和初级运动皮层 (M1) 的局部场电位活动，并描述了随着动物从正常状态向逐渐严重的帕金森状态转变，β 爆发活动如何发生变化。帕金森病与 STN 和 GPi 中低β 频段 (8-20 Hz) 中具有更长持续时间和更高振幅的β 爆发的发生率增加有关，但在 M1 中没有。然而，我们观察到在 PD 中，所有记录部位 (M1、STN 和 GPi) 的β 爆发活动的一致性更大。随着 PD 运动体征严重程度的增加，BGTC 网络中多个节点同时出现的低β 爆发活动提供了令人信服的证据，支持低β 同步振荡在 PD 的潜在病理生理学中发挥重要作用的假说。鉴于其在运动回路中的沉浸感，我们假设这种升高的β 波段活动干扰了 BGTC 网络中信息流的时空处理，导致 PD 中运动功能受损。这项研究填补了关于从正常到逐渐严重的帕金森状态演变过程中，BGTC 网络中β 爆发活动的时间动态和耦合变化的知识空白。我们观察到，β 振荡活动的变化发生在整个 BGTC 中，并且帕金森病的严重程度增加与基底节中持续时间更长、振幅更高的低β 爆发的发生率增加以及 STN、苍白球和运动皮层之间的β 爆发一致性增加有关。这些数据为 BGTC 网络中低β 活动的时间动态变化在帕金森病发病机制中的潜在作用提供了新的见解。
