Parkinsonism-related β oscillations in the primate basal ganglia networks Recent advances and clinical implications

Today, the basal ganglia (BG) network can be viewed as a three-layer neural network in which the striatum and the subthalamic nucleus (STN) are the two BG input structures and together innervate BG downstream structures using GABA and glutamate, respectively. The striatum is larger than the STN and is the main site of dopamine depletion in Parkinson's disease (PD). However, STN is the prime target for deep brain stimulation (DBS) of patients with advanced PD. Traditionally, the efficacy of STN-DBS is attributed to the suppression of the pathological synchronous beta oscillations along the cortico-thalamo BG network. In conventional DBS, stimulation is delivered continuously and equally influences normal and pathological neural activity. A DBS protocol would be therefore more effective if stimulation was only applied when necessary. We recently showed in the non-human primate model of PD that parkinsonism-related beta oscillations resonate across the BG network through the STN, not the striatum. Moreover, we also demonstrated that BG beta oscillations are episodic and albeit extended in parkinsonism also exists in the healthy condition. Thus, not all parkinsonian beta oscillatory episodes are necessarily pathological. Remarkably, the duration of BG beta episodes is more highly impacted than their magnitude in parkinsonism and may be more reliable metric- especially in STN- to discriminate between normal (good) and pathological (bad) beta episodes. Thus, prolonged STN beta episodes is suggested as one of the biomarkers of the pathological neuronal activity in parkinsonism that could be used as a trigger for adaptive DBS.