Background: The efficacy of deep brain stimulation (DBS) - primarily of the subthalamic nucleus (STN) - for advanced Parkinson's disease (PD) is commonly attributed to the suppression of pathological synchronous β oscillations along the cortico-thalamo-basal ganglia network. Conventional continuous high-frequency DBS indiscriminately influences pathological and normal neural activity. The DBS protocol would therefore be more effective if stimulation was only applied when necessary (closed-loop adaptive DBS). Objectives and Methods: Our study aimed to identify a reliable biomarker of the pathological neuronal activity in parkinsonism that could be used as a trigger for adaptive DBS. To this end, we examined the oscillatory features of paired spiking activities recorded in three distinct nodes of the basal ganglia network of 2 African green monkeys before and after induction of parkinsonism (by MPTP intoxication). Results: Parkinsonism-related basal ganglia β oscillations consisted of synchronized time-limited episodes, rather than a continuous stretch, of β oscillatory activity. Episodic basal ganglia β oscillatory activity, although prolonged in parkinsonism, was not necessarily pathological given that short β episodes could also be detected in the healthy state. Importantly, prolongation of the basal ganglia β episodes was more pronounced than their intensification in the parkinsonian state—especially in the STN. Hence, deletion of longer β episodes was more effective than deletion of stronger β episodes in reducing parkinsonian STN synchronized oscillatory activity. Conclusions: Prolonged STN β episodes are pathological in parkinsonism and can be used as optimal trigger for future adaptive DBS applications.
Bibliographical noteFunding Information:
Funding agencies: This work was supported by grants from the Edmond and Lily Safra Center (ELSC) to M.D. and L.I.; the Israel Ministry of Absorption and the Teva National Network of Excellence in Neuroscience (NNE) to L.I.; the Israel-US Binational Science Foundation (BSF) and the Adelis Foundation to Z.I. and H.B.; the European Research Council (ERC), the Israel Science Foundation (ISF), the German Israel Science Foundation (GIF), the Canadian Friends of the Hebrew University, the Rosetrees and Vorst Foundations, and the Simone and Bernard Guttman Chair in Brain Research to H.B.
© 2018 International Parkinson and Movement Disorder Society
- MPTP-treated monkey
- Parkinson's disease
- basal ganglia
- deep brain stimulation
- β oscillations