Neurobiology of Disease (Dec 2016)
Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson's disease
Abstract
Subthalamic nucleus (STN) local field potential (LFP) recordings demonstrate beta (13–30 Hz) band oscillations in Parkinson's disease (PD) defined as elevations of spectral power. The amount of attenuation of beta band power on therapeutic levels of high frequency (HF) deep brain stimulation (DBS) and/or dopaminergic medication has been correlated with the degree of improvement in bradykinesia and rigidity from the therapy, which has led to the suggestion that elevated beta band power is a marker of PD motor disability. A fundamental question has not been answered: whether there is a prolonged attenuation of beta band power after withdrawal of chronic HF DBS and whether this is related to a lack of progression or even improvement in the underlying motor disability.Until now, in human PD subjects, STN LFP recordings were only attainable in the peri-operative period and after short periods of stimulation. For the first time, using an investigational, implanted sensing neurostimulator (Activa® PC + S, Medtronic, Inc.), STN LFPs and motor disability were recorded/assessed after withdrawal of chronic (6 and 12 month) HF DBS in freely moving PD subjects. Beta band power was similar within 14 s and 60 min after stimulation was withdrawn, suggesting that “off therapy” experiments can be conducted almost immediately after stimulation is turned off. After withdrawal of 6 and 12 months of STN DBS, beta band power was significantly lower (P < 0.05 at 6 and 12 months) and off therapy UPDRS scores were better (P < 0.05 at 12 months) compared to before DBS was started. The attenuation in beta band power was correlated with improvement in motor disability scores (P < 0.05). These findings were supported by evidence of a gradual increase in beta band power in two unstimulated STNs after 24 months and could not be explained by changes in lead impedance. This suggests that chronic HF DBS exerts long-term plasticity in the sensorimotor network, which may contribute to a lack of progression in underlying motor disability in PD.
