Bharti Eesha, DeNicola Adele L, Yu Ying, Verma Ajay K, Schneck David, Mohanty Biswaranjan, Fiecas Mark, Yao Hongyu, Wang Jing, Johnson Luke A, Vitek Jerrold L
Computational Neurostimulation Research Program, Noninvasive Neuromodulation Unit, Experimental and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
Department of Neurology, University of Minnesota, Minneapolis, MN, United States.
Neurobiol Dis. 2025 Aug 29;215:107075. doi: 10.1016/j.nbd.2025.107075.
Mounting evidence suggests that elevated beta oscillatory activity in the basal ganglia thalamocortical (BGTC) network is associated with the cardinal motor signs in people with Parkinson's disease (PD). The evolution of abnormal beta oscillatory activity across the BGTC network as motor signs emerge, however, is not well understood. The goal of this study was to investigate whether beta oscillatory activity in the BGTC network changes prior to and how it evolves during the emergence of mild parkinsonian motor signs. To address this question, we performed simultaneous neural recordings in the subthalamic nucleus (STN), the internal and external globus pallidus (GPi and GPe), motor thalamus (Th), and the primary motor cortex (M1) in a progressive, non-human primate (NHP) model of PD using sequential injections of low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The emergence of mild PD motor signs was associated with an increase in STN, GPi, GPe, and Th beta power in both subjects. Although changes in cortical beta power were noted in both subjects before the emergence of motor signs, the direction of change differed between subjects. Our data provide compelling evidence that changes in beta oscillatory activity occur early and are found across the BGTC network during the initial expression of parkinsonian motor signs. These findings support the hypothesis that abnormal beta oscillatory activity in the BGTC network plays a significant role in the neural pathogenesis that underlies the development of PD motor signs.
越来越多的证据表明,基底神经节丘脑皮质(BGTC)网络中β振荡活动增强与帕金森病(PD)患者的主要运动症状相关。然而,随着运动症状的出现,BGTC网络中异常β振荡活动的演变情况尚不清楚。本研究的目的是调查BGTC网络中的β振荡活动在轻度帕金森运动症状出现之前是否发生变化,以及在其出现过程中如何演变。为了解决这个问题,我们在一种渐进性非人类灵长类动物(NHP)帕金森病模型中,通过连续注射低剂量1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP),同时在丘脑底核(STN)、苍白球内侧部和外侧部(GPi和GPe)、运动丘脑(Th)和初级运动皮层(M1)进行神经记录。两名受试者轻度帕金森运动症状的出现均与STN、GPi、GPe和Th区β功率增加有关。虽然在运动症状出现之前,两名受试者的皮质β功率均有变化,但变化方向在受试者之间有所不同。我们的数据提供了令人信服的证据,表明β振荡活动的变化在帕金森运动症状初始表现期间很早就出现了,并且在整个BGTC网络中都能发现。这些发现支持了这样一种假设,即BGTC网络中异常的β振荡活动在帕金森运动症状发展背后的神经发病机制中起重要作用。