Evoked potentials reveal neural circuits engaged by human deep brain stimulation

Abstract

Background: Deep brain stimulation (DBS) is an effective therapy for reducing the motor symptoms of Parkinson’s disease, but the mechanisms of action of DBS and neural correlates of symptoms remain unknown. Objective: To use the neural response to DBS to reveal connectivity of neural circuits and interactions between groups of neurons as potential mechanisms for DBS. Methods: We recorded activity evoked by DBS of the subthalamic nucleus (STN) in humans with Parkinson’s disease. In follow up experiments we also simultaneously recorded activity in the contralateral STN or the ipsilateral globus pallidus from both internal (GPi) and external (GPe) segments. Results: DBS local evoked potentials (DLEPs) were stereotyped across subjects, and a biophysical model of reciprocal connections between the STN and the GPe recreated DLEPs. Simultaneous STN and GP recordings during STN DBS demonstrate that DBS evoked potentials were present throughout the basal ganglia and confirmed that DLEPs arose from the reciprocal connections between the STN and GPe. The shape and amplitude of the DLEPs were dependent on the frequency and duration of DBS and were correlated with resting beta band oscillations. In the frequency domain, DLEPs appeared as a 350 Hz high frequency oscillation (HFO) independent of the frequency of DBS. Conclusions: DBS evoked potentials suggest that the intrinsic dynamics of the STN and GP are highly interlinked and may provide a promising new biomarker for adaptive DBS.

Keywords

• DBS
• Parkinson’’s disease
• Subthalamic nucleus
• Globus pallidus