Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations.

Abstract

The objective of this study was to investigate the hypothesis that attenuation of subthalamic nucleus (STN) alpha-/beta-band oscillations is causal to improvement in bradykinesia. STN local field potentials from a sensing neurostimulator (Activa® PC+S; Medtronic, Inc.) and kinematics from wearable sensors were recorded simultaneously during 60- and 140-Hz deep brain stimulation (DBS) in 9 freely moving PD subjects (15 STNs) performing repetitive wrist flexion-extension. Kinematics were recorded during 20-Hz DBS in a subgroup. Both 60- and 140-Hz DBS improved the angular velocity and frequency of movement (P=0.002 and P=0.029, respectively, for 60 Hz; P<0.001 and P<0.001, respectively, for 140 Hz), but 60-Hz DBS did not attenuate beta-band power (13-30 Hz). In fact, 60-Hz DBS amplified alpha/low-beta (11-15 Hz, P=0.007) and attenuated high-beta power (19-27 Hz, P<0.001), whereas 140-Hz DBS broadly attenuated beta power (15-30 Hz, P<0.001). Only 60-Hz DBS improved the regularity of angular range (P=0.046) and 20-Hz DBS did not worsen bradykinesia. There was no correlation between beta-power modulation and bradykinesia. These novel results obtained from freely moving PD subjects demonstrated that both 140- and 60-Hz DBS improved bradykinesia and attenuated high beta oscillations; however, 60-Hz DBS amplified a subband of alpha/low-beta oscillations, and DBS at a beta-band frequency did not worsen bradykinesia. Based on recent literature, we suggest that both 140- and 60-Hz DBS decouple the cortico-STN hyperdirect pathway, whereas 60-Hz DBS increases coupling within striato-STN circuitry. These results inform future algorithms for closed-loop DBS in PD. © 2016 International Parkinson and Movement Disorder Society.