Short pulse width widens the therapeutic window of subthalamic neurostimulation

We explored the impact of pulse durations <60 μsec on the therapeutic window of subthalamic neurostimulation in Parkinson's disease. Current thresholds for full rigidity control and first muscle contractions were evaluated at pulse durations between 20 and 120 μsec during a monopolar review session in four patients. The average therapeutic window was 2.16 mA at 60 μsec, which proportionally increased by 182% at 30 μsec, while decreasing by 46% at 120 μsec. Measured chronaxies and model data suggest, that pulse durations <60 μsec lead to a focusing of the neurostimulation effect on smaller diameter axons close to the electrode while avoiding stimulation of distant pyramidal tract fibers.

[1]  Cameron C McIntyre,et al.  Evaluation of novel stimulus waveforms for deep brain stimulation , 2010, Journal of neural engineering.

[2]  G. Deuschl,et al.  Physiological and anatomical decomposition of subthalamic neurostimulation effects in essential tremor. , 2014, Brain : a journal of neurology.

[3]  Hugh J. McDermott,et al.  Comment on: Short pulse width widens the therapeutic window of subthalamic neurostimulation , 2015, Annals of clinical and translational neurology.

[4]  C. McIntyre,et al.  Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle. , 2002, Journal of neurophysiology.

[5]  J. B. Ranck,et al.  Which elements are excited in electrical stimulation of mammalian central nervous system: A review , 1975, Brain Research.

[6]  Per Capita,et al.  About the authors , 1995, Machine Vision and Applications.

[7]  C. McIntyre,et al.  Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. , 2002, Journal of neurophysiology.

[8]  Cameron C. McIntyre,et al.  Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region , 2012, Brain Stimulation.

[9]  P. A. House,et al.  Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease: A Randomized Controlled Trial , 2009 .

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

[11]  T. Kita,et al.  The Subthalamic Nucleus Is One of Multiple Innervation Sites for Long-Range Corticofugal Axons: A Single-Axon Tracing Study in the Rat , 2012, The Journal of Neuroscience.

[12]  Bart Nuttin,et al.  Chronaxie calculated from current–duration and voltage–duration data , 2000, Journal of Neuroscience Methods.

[13]  J. Volkmann,et al.  Basic algorithms for the programming of deep brain stimulation in Parkinson's disease , 2006, Movement disorders : official journal of the Movement Disorder Society.

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

[15]  D. Mcneal.  Analysis of a Model for Excitation of Myelinated Nerve , 1976, IEEE Transactions on Biomedical Engineering.

[16]  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.

[17]  B. M. ter Haar Romeny,et al.  Structural and Resting State Functional Connectivity of the Subthalamic Nucleus: Identification of Motor STN Parts and the Hyperdirect Pathway , 2012, PloS one.

[18]  C. McIntyre,et al.  Differences among implanted pulse generator waveforms cause variations in the neural response to deep brain stimulation , 2007, Clinical Neurophysiology.

[19]  A. Morel,et al.  Multiarchitectonic and stereotactic atlas of the human thalamus , 1997, The Journal of comparative neurology.

[20]  C. McIntyre,et al.  Sources and effects of electrode impedance during deep brain stimulation , 2006, Clinical Neurophysiology.

[21]  Jaimie M. Henderson,et al.  Probabilistic analysis of activation volumes generated during deep brain stimulation , 2011, NeuroImage.

[22]  Günther Deuschl,et al.  Stimulation site within the MRI‐defined STN predicts postoperative motor outcome , 2012, Movement disorders : official journal of the Movement Disorder Society.

[23]  Danny C. W. Chan,et al.  Therapeutic Deep Brain Stimulation in Parkinsonian Rats Directly Influences Motor Cortex , 2012, Neuron.

[24]  J Holsheimer,et al.  Identification of the target neuronal elements in electrical deep brain stimulation , 2000, The European journal of neuroscience.