Sixty hertz neurostimulation amplifies subthalamic neural synchrony in Parkinson's disease

Abstract

High frequency subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor signs of Parkinson's disease (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony. Here we demonstrate for the first time that during intra-operative 60 Hz STN DBS, one or more bands of resting state neural synchrony were amplified in the STN in PD. We recorded intra-operative STN resting state local field potentials (LFPs) from twenty-eight STNs in seventeen PD subjects after placement of the DBS lead (model 3389, Medtronic, Inc.) before and during three randomized neurostimulation sets (130 Hz/1.35V, 130 Hz/2V, 60 Hz/2V). During 130 Hz/2V DBS, baseline (no DBS) STN alpha (8-12 Hz) and beta (13-35 Hz) band power decreased (N=14, P < 0.001 for both), whereas during 60 Hz/2V DBS, alpha band and peak frequency power increased (P = 0.012, P = 0.007, respectively). The effect of 60 Hz/2V DBS opposed that of power-equivalent (130 Hz/1.35V) DBS (alpha: P < 0.001, beta: P = 0.006). These results show that intra-operative 60 Hz STN DBS amplified whereas 130 Hz STN DBS attenuated resting state neural synchrony in PD; the effects were frequency-specific. We demonstrate that neurostimulation may be useful as a tool to selectively modulate resting state resonant bands of neural synchrony and to investigate its influence on motor and non-motor behaviors in PD and other neuropsychiatric diseases.

Fig 1. Example STN during the different stimulation sets.

A, B, C, and D are raw waveforms and spectrograms from the baseline epoch, 130 Hz/2V DBS epoch, 60 Hz/2V DBS epoch, and 130 Hz/1.35V DBS epoch, respectively. Spectrograms are displayed with 99% window overlap. E: Relative PSD traces of the four epochs. Black = baseline; red = 130 Hz/2V; blue = 60 Hz/2V; green = 130 Hz/1.35V. Colored dashed lines represent 95% confidence intervals for each spectrum.

Fig 2. Peak detection for all fourteen sides.

A—N are absolute PSDs from all fourteen recordings. Black = baseline; red = 60 Hz/2V; dashed = 130 Hz/2V. Arrows indicate where peaks were detected by the algorithm, and the color of an arrow corresponds to its PSD spectrum. Black asterisks on J (one for 60 Hz/2V) and K (two, one for 60 Hz/2V and one for baseline) indicate peaks chosen visually.