Evoked potentials reveal neural circuits engaged by human deep brain stimulation

• Published in: Brain stimulation Vol. 13; no. 6; pp. 1706 - 1718
• Main Authors: Schmidt, Stephen L., Brocker, David T., Swan, Brandon D., Turner, Dennis A., Grill, Warren M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020; Elsevier
• Subjects: Aged; Basal Ganglia - physiology; DBS; Deep Brain Stimulation - methods; Evoked Potentials, Motor - physiology; Female; Globus pallidus; Globus Pallidus - physiology; Humans; Male; Middle Aged; Nerve Net - physiology; Parkinson Disease - physiopathology; Parkinson Disease - therapy; Parkinson’’s disease; Rest - physiology; Stereotaxic Techniques; Subthalamic nucleus; Subthalamic Nucleus - physiology; Globus pallidus; Subthalamic nucleus; DBS; Parkinson’’s disease
• ISSN: 1935-861X; 1876-4754; 1876-4754
• DOI: 10.1016/j.brs.2020.09.028

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. To use the neural response to DBS to reveal connectivity of neural circuits and interactions between groups of neurons as potential mechanisms for DBS. 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. 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. 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. •DBS evoked low-latency responses within the STN, GPi, and GPe.•The amplitude and latency of DLEPs changed with continued DBS.•A biophysical model suggests that DLEPs arise from reciprocal STN GPe connections.