A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo

Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design.

[1]  S. Cogan.  Neural stimulation and recording electrodes. , 2008, Annual review of biomedical engineering.

[2]  Robert Cowan,et al.  A Systematic Review of Electric-Acoustic Stimulation , 2013, Trends in amplification.

[3]  J. Bullier,et al.  Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter II. Evidence from selective inactivation of cell bodies and axon initial segments , 1998, Experimental Brain Research.

[4]  W. Dehaene,et al.  A high-voltage output driver in a 2.5-V 0.25-/spl mu/m CMOS technology , 2005, IEEE Journal of Solid-State Circuits.

[5]  K.D. Wise,et al.  A three-dimensional neural recording microsystem with implantable data compression circuitry , 2005, IEEE Journal of Solid-State Circuits.

[6]  Richard B. North,et al.  Neural Interface Devices: Spinal Cord Stimulation Technology , 2008, Proceedings of the IEEE.

[7]  Maysam Ghovanloo,et al.  Switched-capacitor based implantable low-power wireless microstimulating systems , 2006, 2006 IEEE International Symposium on Circuits and Systems.

[8]  Maurits Ortmanns,et al.  A Neural Stimulator Frontend With High-Voltage Compliance and Programmable Pulse Shape for Epiretinal Implants , 2012, IEEE Journal of Solid-State Circuits.

[9]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[10]  K. Wise,et al.  A three-dimensional microelectrode array for chronic neural recording , 1994, IEEE Transactions on Biomedical Engineering.

[11]  Jyh-Yeong Chang,et al.  Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording , 2012, Journal of neural engineering.

[12]  Richard Bayford,et al.  Evaluating the impact of the deep brain stimulation induced electric field on subthalamic neurons: A computational modelling study , 2010, Journal of Neuroscience Methods.

[13]  R.R. Harrison,et al.  A Low-Power Integrated Circuit for a Wireless 100-Electrode Neural Recording System , 2006, IEEE Journal of Solid-State Circuits.

[14]  Michael S. Okun,et al.  Management of Deep Brain Stimulator Battery Failure: Battery Estimators, Charge Density, and Importance of Clinical Symptoms , 2013, PloS one.

[15]  Robert Rieger,et al.  An implanted system for multi-site nerve cuff-based ENG recording using velocity selectivity , 2009 .

[16]  M. Ortmanns,et al.  A 0.1mm/sup 2/, Digitally Programmable Nerve Stimulation Pad Cell with High-Voltage Capability for a Retinal Implant , 2006, 2006 IEEE International Solid State Circuits Conference - Digest of Technical Papers.

[17]  F. Solzbacher,et al.  In vitro comparison of sputtered iridium oxide and platinum-coated neural implantable microelectrode arrays , 2010, Biomedical materials.

[18]  J. Bullier,et al.  Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter I. Evidence from chronaxie measurements , 1998, Experimental Brain Research.

[19]  Jonathan E Rubin,et al.  Deep brain stimulation entrains local neuronal firing in human globus pallidus internus. , 2013, Journal of neurophysiology.

[20]  Mohamad Sawan,et al.  A ±9 V fully integrated CMOS electrode driver for high-impedance microstimulation , 2009, 2009 52nd IEEE International Midwest Symposium on Circuits and Systems.

[21]  K. Foote,et al.  Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes , 2014, Neurotherapeutics.

[22]  Hao Jiang,et al.  A Low-Frequency Versatile Wireless Power Transfer Technology for Biomedical Implants , 2013, IEEE Transactions on Biomedical Circuits and Systems.

[23]  Michael S Okun,et al.  Deep brain stimulation (DBS) at the interface of neurology and psychiatry. , 2013, The Journal of clinical investigation.

[24]  D. Denys,et al.  [Deep brain stimulation for psychiatric disorders]. , 2018, Nederlands tijdschrift voor geneeskunde.

[25]  Bettina H. Bewernick,et al.  Neuromodulation for Treatment Resistant Depression: State of the Art and Recommendations for Clinical and Scientific Conduct , 2013, Brain Topography.

[26]  M. Okun,et al.  Deep brain stimulation and ablation for obsessive compulsive disorder: evolution of contemporary indications, targets and techniques , 2014, The International journal of neuroscience.

[27]  T. Duong,et al.  fMRI of Deep Brain Stimulation at the Rat Ventral Posteromedial Thalamus , 2014, Brain Stimulation.

[28]  Wim Dehaene,et al.  A high-voltage output driver in a 2.5-V 0.25-μm CMOS technology , 2005 .

[29]  Y. Chen,et al.  Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain , 2009, Journal of Neuroscience Methods.

[30]  Greg Worrell,et al.  Long-Term Measurement of Impedance in Chronically Implanted Depth and Subdural Electrodes During Responsive Neurostimulation in Humans , 2013, Brain Stimulation.

[31]  Charles A. Miller,et al.  Auditory nerve responses to monophasic and biphasic electric stimuli , 2001, Hearing Research.

[32]  M. Sawan,et al.  A flexible high voltage biphasic current-controlled stimulator , 2006, 2006 IEEE Biomedical Circuits and Systems Conference.

[33]  Patrick Dupont,et al.  Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: a key role for the subgenual anterior cingulate and ventral striatum. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[34]  Mohamad Sawan,et al.  Wireless monitoring of electrode-tissues interfaces for long term characterization , 2008 .

[35]  E. Pralong,et al.  Chronic deep brain stimulation in mesial temporal lobe epilepsy , 2011, Seizure.

[36]  Drew S. Kern,et al.  Deep Brain Stimulation , 2007, The neurologist.

[37]  A Low-Cost Multi-Electrode Array System for the Simultaneous Acquisition of Electrophysiological Signal and Cellular Morphology , 2012 .

[38]  C. McIntyre,et al.  Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both , 2004, Clinical Neurophysiology.

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

[40]  T. Lehmann,et al.  The Design and Testing of an Epi-Retinal Vision Prosthesis Neurostimulator Capable of Concurrent Parallel Stimulation , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[41]  Daniel R. Merrill,et al.  Electrical stimulation of excitable tissue: design of efficacious and safe protocols , 2005, Journal of Neuroscience Methods.

[42]  V. Edgerton,et al.  Toward an implantable functional electrical stimulation device to correct strabismus. , 2009, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[43]  K. Zaghloul,et al.  Temporal macrodynamics and microdynamics of the postoperative impedance at the tissue–electrode interface in deep brain stimulation patients , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[44]  F. Henn.  Circuits, Cells, and Synapses: Toward a New Target for Deep Brain Stimulation in Depression , 2012, Neuropsychopharmacology.

[45]  P. L. Albernaz,et al.  History of cochlear implants , 2014, Brazilian journal of otorhinolaryngology.

[46]  P. Irazoqui-Pastor,et al.  In-vivo EEG recording using a wireless implantable neural transceiver , 2003, First International IEEE EMBS Conference on Neural Engineering, 2003. Conference Proceedings..

[47]  Jin-Chern Chiou,et al.  Development of a Three Dimensional Neural Sensing Device by a Stacking Method , 2010, Sensors.

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

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

[50]  Laura Cif,et al.  Evolution of Brain Impedance in Dystonic Patients Treated by GPi Electrical Stimulation , 2004, Neuromodulation : journal of the International Neuromodulation Society.