A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson's disease - A pilot study

Gerrit E. Gmel, Tara J. Hamilton, Milan Obradovic, Robert B. Gorman, Peter S. Single, Helen J. Chenery, Terry Coyne, Peter A. Silburn, John L. Parker

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson's disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

Original languageEnglish
Article number066013
JournalJournal of Neural Engineering
Volume12
Issue number6
DOIs
Publication statusPublished - 2015
Externally publishedYes

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Deep Brain Stimulation
Biomarkers
Parkinson Disease
Brain
Subthalamic Nucleus
Nerve Tissue
Equipment and Supplies
Microelectrodes
Therapeutics
Basal Ganglia
Rigidity
Artifacts
Surgery
Action Potentials
Tissue
Imaging techniques
Research

Cite this

Gmel, G. E., Hamilton, T. J., Obradovic, M., Gorman, R. B., Single, P. S., Chenery, H. J., ... Parker, J. L. (2015). A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson's disease - A pilot study. Journal of Neural Engineering, 12(6), [066013]. https://doi.org/10.1088/1741-2560/12/6/066013
Gmel, Gerrit E. ; Hamilton, Tara J. ; Obradovic, Milan ; Gorman, Robert B. ; Single, Peter S. ; Chenery, Helen J. ; Coyne, Terry ; Silburn, Peter A. ; Parker, John L. / A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson's disease - A pilot study. In: Journal of Neural Engineering. 2015 ; Vol. 12, No. 6.
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abstract = "Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson's disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.",
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Gmel, GE, Hamilton, TJ, Obradovic, M, Gorman, RB, Single, PS, Chenery, HJ, Coyne, T, Silburn, PA & Parker, JL 2015, 'A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson's disease - A pilot study' Journal of Neural Engineering, vol. 12, no. 6, 066013. https://doi.org/10.1088/1741-2560/12/6/066013

A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson's disease - A pilot study. / Gmel, Gerrit E.; Hamilton, Tara J.; Obradovic, Milan; Gorman, Robert B.; Single, Peter S.; Chenery, Helen J.; Coyne, Terry; Silburn, Peter A.; Parker, John L.

In: Journal of Neural Engineering, Vol. 12, No. 6, 066013, 2015.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson's disease - A pilot study

AU - Gmel, Gerrit E.

AU - Hamilton, Tara J.

AU - Obradovic, Milan

AU - Gorman, Robert B.

AU - Single, Peter S.

AU - Chenery, Helen J.

AU - Coyne, Terry

AU - Silburn, Peter A.

AU - Parker, John L.

PY - 2015

Y1 - 2015

N2 - Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson's disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

AB - Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson's disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

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DO - 10.1088/1741-2560/12/6/066013

M3 - Article

VL - 12

JO - Journal of Neural Engineering

JF - Journal of Neural Engineering

SN - 1741-2552

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