Long-Term Task- and Dopamine-Dependent Dynamics of Subthalamic Local Field Potentials in Parkinson's Disease.

Sara J Hanrahan,Monique Giroux,Mohammad H Mahoor,Sierra Farris,Anne K Silverman,Aaron Haug,Joshua J Nedrud,Bradley S Davidson,Jun Jason Zhang,Adam Olding Hebb

doi:10.3390/brainsci6040057

Abstract

Subthalamic nucleus (STN) local field potentials (LFP) are neural signals that have been shown to reveal motor and language behavior, as well as pathological parkinsonian states. We use a research-grade implantable neurostimulator (INS) with data collection capabilities to record STN-LFP outside the operating room to determine the reliability of the signals over time and assess their dynamics with respect to behavior and dopaminergic medication. Seven subjects were implanted with the recording augmented deep brain stimulation (DBS) system, and bilateral STN-LFP recordings were collected in the clinic over twelve months. Subjects were cued to perform voluntary motor and language behaviors in on and off medication states. The STN-LFP recorded with the INS demonstrated behavior-modulated desynchronization of beta frequency (13–30 Hz) and synchronization of low gamma frequency (35–70 Hz) oscillations. Dopaminergic medication did not diminish the relative beta frequency oscillatory desynchronization with movement. However, movement-related gamma frequency oscillatory synchronization was only observed in the medication on state. We observed significant inter-subject variability, but observed consistent STN-LFP activity across recording systems and over a one-year period for each subject. These findings demonstrate that an INS system can provide robust STN-LFP recordings in ambulatory patients, allowing for these signals to be recorded in settings that better represent natural environments in which patients are in a variety of medication states.

Highlights

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) therapy in patients with Parkinson’s disease (PD)
Our study examined the influence of medication and behavior on Subthalamic nucleus (STN)-Local field potentials (LFP) activity in PD patients over one year
Many groups are currently investigating appropriate neurophysiological biomarkers to be used as a feedback signal in a closed-loop DBS system [11,49,60,61,62]

Summary

Introduction

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) therapy in patients with Parkinson’s disease (PD). DBS system with active modulation of stimulation by appropriate physiological control variables may reduce these side effects, while providing maximum therapeutic benefit of PD motor symptoms [7,8,9,10,11]. Local field potentials (LFP) recorded from the STN have the potential to be a robust control signal to indicate a change in a patient’s state [12,13,14,15]. STN-LFPs have been shown to correlate with a patient’s Parkinson’s disease symptom state [16], levodopa medication level [17,18], behavior [19,20,21]. LFP signals are stable over long periods of time, as evidenced by recordings from the motor cortex [22] and STN [23,24], a necessary characteristic for a feedback signal in a closed-loop DBS system

Methods

Results

Discussion

Conclusion