A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson’s disease—a pilot study

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.

[1]  Philip J. Hahn,et al.  Network perspectives on the mechanisms of deep brain stimulation , 2010, Neurobiology of Disease.

[2]  T. Wichmann,et al.  Cortical Potentials Evoked by Deep Brain Stimulation in the Subthalamic Area , 2011, Front. Syst. Neurosci..

[3]  Matthew D. Johnson,et al.  Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey , 2009, Experimental Neurology.

[4]  A. Lang,et al.  Ten-year outcome of subthalamic stimulation in Parkinson disease: a blinded evaluation. , 2011, Archives of neurology.

[5]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[6]  K. Burchiel,et al.  Randomized trial of deep brain stimulation for Parkinson disease , 2012, Neurology.

[7]  E. Montgomery,et al.  Basal ganglia physiology and pathophysiology: a reappraisal. , 2007, Parkinsonism & related disorders.

[8]  G. Deuschl,et al.  A randomized trial of deep-brain stimulation for Parkinson's disease. , 2006, The New England journal of medicine.

[9]  Dean M. Karantonis,et al.  Compound action potentials recorded in the human spinal cord during neurostimulation for pain relief , 2012, PAIN.

[10]  B. Guthrie,et al.  Short latency activation of cortex by clinically effective thalamic brain stimulation for tremor , 2012, Movement disorders : official journal of the Movement Disorder Society.

[11]  S. Haber,et al.  Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism , 2011, Neuron.

[12]  R. Alterman,et al.  Referring patients for deep brain stimulation: an improving practice. , 2011, Archives of neurology.

[13]  Michael J. Jutras,et al.  Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. , 2007, Journal of neurophysiology.

[14]  Keith Wheatley,et al.  Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial , 2010, The Lancet Neurology.

[15]  David J Brooks,et al.  Optimizing levodopa therapy for Parkinson’s disease with levodopa/carbidopa/entacapone: implications from a clinical and patient perspective , 2008, Neuropsychiatric disease and treatment.

[16]  Brian Hyland,et al.  Cortical effects of subthalamic stimulation correlate with behavioral recovery from dopamine antagonist induced akinesia. , 2009, Cerebral cortex.

[17]  Warren M. Grill,et al.  Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation , 2008, Journal of Computational Neuroscience.

[18]  J. Henderson,et al.  High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson's disease , 2012, Front. Hum. Neurosci..

[19]  Grant D. Huang,et al.  Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. , 2009, JAMA.

[20]  H. Steinbusch,et al.  The functional role of the subthalamic nucleus in cognitive and limbic circuits , 2005, Progress in Neurobiology.

[21]  G. Deuschl,et al.  Accuracy and Distortion of Deep Brain Stimulation Electrodes on Postoperative MRI and CT , 2008, Zentralblatt fur Neurochirurgie.

[22]  N. Matsukawa,et al.  Complications of subthalamic nucleus stimulation in Parkinson's disease. , 2011, Neurologia medico-chirurgica.

[23]  A. Bentivoglio,et al.  Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants. , 2010, Brain : a journal of neurology.

[24]  Tara Julia Hamilton,et al.  A new biomarker for closed-loop deep brain stimulation in the subthalamic nucleus for patients with Parkinson's disease , 2014, 2014 IEEE Biomedical Circuits and Systems Conference (BioCAS) Proceedings.

[25]  A. Rezai,et al.  Deep Brain Stimulation for Neurological Disorders , 2012, IEEE Reviews in Biomedical Engineering.

[26]  P Ashby,et al.  Potentials recorded at the scalp by stimulation near the human subthalamic nucleus , 2001, Clinical Neurophysiology.

[27]  J. Villemure,et al.  Effect on mood of subthalamic DBS for Parkinson’s disease A consecutive series of 24 patients , 2002, Neurology.

[28]  M. Lowery,et al.  Simulation of Cortico-Basal Ganglia Oscillations and Their Suppression by Closed Loop Deep Brain Stimulation , 2013, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[29]  Warren M Grill,et al.  Neural origin of evoked potentials during thalamic deep brain stimulation. , 2013, Journal of neurophysiology.

[30]  P. Silburn,et al.  Rapid subthalamic nucleus deep brain stimulation lead placement utilising CT/MRI fusion, microelectrode recording and test stimulation. , 2006, Acta neurochirurgica. Supplement.

[31]  P. Brown,et al.  Adaptive Deep Brain Stimulation In Advanced Parkinson Disease , 2013, Annals of neurology.

[32]  Alexander R. Kent,et al.  Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact , 2012, Journal of neural engineering.

[33]  P. Krack,et al.  Long‐term outcomes of surgical therapies for Parkinson's disease , 2012, Movement disorders : official journal of the Movement Disorder Society.

[34]  Philippe Mailly,et al.  Evidence for a direct subthalamo‐cortical loop circuit in the rat , 2008, The European journal of neuroscience.

[35]  A. Benabid,et al.  Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[36]  E. A. Brown,et al.  Stimulation and recording of neural tissue, closing the loop on the artifact , 2008, 2008 IEEE International Symposium on Circuits and Systems.

[37]  Erwin B. Montgomery,et al.  Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation , 2012, Front. Integr. Neurosci..

[38]  Erwin B. Montgomery,et al.  Mechanisms of action of deep brain stimulation (DBS) , 2008, Neuroscience & Biobehavioral Reviews.

[39]  D. Graupe,et al.  Pathological tremor prediction using surface electromyogram and acceleration: potential use in ‘ON–OFF’ demand driven deep brain stimulator design , 2013, Journal of neural engineering.

[40]  G. Deuschl,et al.  The cost-effectiveness of deep brain stimulation in combination with best medical therapy, versus best medical therapy alone, in advanced Parkinson’s disease , 2013, Journal of Neurology.

[41]  Markus Butz,et al.  Distinct oscillatory STN-cortical loops revealed by simultaneous MEG and local field potential recordings in patients with Parkinson's disease , 2011, NeuroImage.

[42]  Mandy Miller Koop,et al.  Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease , 2006, Experimental Neurology.

[43]  O. Jensen,et al.  Shaping Functional Architecture by Oscillatory Alpha Activity: Gating by Inhibition , 2010, Front. Hum. Neurosci..

[44]  W. Grill,et al.  Closed-Loop Control of Deep Brain Stimulation: A Simulation Study , 2011, IEEE Transactions on Neural Systems and Rehabilitation Engineering.