Alterations in beta oscillatory activity occur with the emergence of parkinsonian motor signs across the basal ganglia-thalamocortical network

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. • Excessive beta activity is a neural biomarker of motor signs in advanced PD. • The role of beta activity in the early emergence of PD motor signs is unclear. • Early expression of PD motor signs is associated with abnormal BGTC beta activity. • The results suggest abnormal beta activity occurs early and across multiple regions of the BGTC network with the emergence of PD motor signs.