Spontaneous and “event-related” motor cortex oscillations in the beta (15–30 Hz) frequency range are well-established phenomena. However, the precise functional significance of these features is uncertain. An understanding of the specific function is of importance for the treatment of Parkinson's disease (PD), where attenuation of augmented beta throughout the motor network coincides with functional improvement. Previous research using a discrete movement task identified normalization of elevated spontaneous beta and postmovement beta rebound following GABAergic modulation. Here, we explore the effects of the gamma-aminobutyric acid type A modulator, zolpidem, on beta power during the performance of serial movement in 17 (15M, 2F; mean age, 66 ± 6.3 years) PD patients, using a repeated-measures, double-blinded, randomized, placebo-control design. Motor symptoms were monitored before and after treatment, using time-based Unified Parkinson's Disease Rating Scale measurements and beta oscillations in primary motor cortex (M1) were measured during a serial-movement task, using magnetoencephalography. We demonstrate that a cumulative increase in M1 beta power during a 10-s tapping trial is reduced following zolpidem, but not placebo, which is accompanied by an improvement in movement speed and efficacy. This work provides a clear mechanism for the generation of abnormally elevated beta power in PD and demonstrates that perimovement beta accumulation drives the slowing, and impaired initiation, of movement. These findings further indicate a role for GABAergic modulation in bradykinesia in PD, which merits further exploration as a therapeutic target.
|Journal||Frontiers in Neurology|
|Publication status||Published - 20 Dec 2019|
Bibliographical note© 2019 Prokic, Stanford, Woodhall, Williams and Hall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Funding: Parkinson’s UK (G-1008), the Biotechnology and Biological Sciences Research Council (BB/H003894/1) and The Wellcome Trust for funding the MEG system (088314/Z/09/Z).
Prokic, E., Woodhall, G. L., Williams, A. C., Stanford, I., & Hall, S. (2019). Bradykinesia is driven by cumulative beta power during continuous movement and alleviated by GABAergic modulation in Parkinson’s disease. Frontiers in Neurology, 10, . https://doi.org/10.3389/fneur.2019.01298