Longer β oscillatory episodes reliably identify pathological subthalamic activity in Parkinsonism

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.