Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording

An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode-tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 µm thick and with a diameter of 16 µm). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode-electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (ΣSSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models.

[1]  E. Maynard,et al.  A technique to prevent dural adhesions to chronically implanted microelectrode arrays , 2000, Journal of Neuroscience Methods.

[2]  Thomas J. Brozoski,et al.  Marking multi-channel silicon-substrate electrode recording sites using radiofrequency lesions , 2006, Journal of Neuroscience Methods.

[3]  C. McIntyre,et al.  Finite Element Analysis of the Current-Density and Electric Field Generated by Metal Microelectrodes , 2001, Annals of Biomedical Engineering.

[4]  C. McIntyre,et al.  Current steering to control the volume of tissue activated during deep brain stimulation , 2008, Brain Stimulation.

[5]  In-Seop Lee,et al.  Characterization of iridium film as a stimulating neural electrode. , 2002, Biomaterials.

[6]  R. Emmers Somesthetic system of the rat , 1988 .

[7]  C. McIntyre,et al.  Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition. , 2004, Journal of neurophysiology.

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

[9]  Dong-il Dan Cho,et al.  Roughened polysilicon for low impedance microelectrodes in neural probes , 2003 .

[10]  M. Bikson,et al.  Bio-Heat Transfer Model of Deep Brain Stimulation Induced Temperature changes , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[11]  Michael L. Hines,et al.  The NEURON Book , 2006 .

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

[13]  Rudra Pratap,et al.  Material selection for MEMS devices , 2007 .

[14]  F. Rattay Analysis of Models for External Stimulation of Axons , 1986, IEEE Transactions on Biomedical Engineering.

[15]  M. Madou Fundamentals of microfabrication : the science of miniaturization , 2002 .

[16]  C. McIntyre,et al.  Electric field and stimulating influence generated by deep brain stimulation of the subthalamic nucleus , 2004, Clinical Neurophysiology.

[17]  Stephen C. Jacobsen,et al.  Microfabricated cylindrical multielectrodes for neural stimulation , 2006, IEEE Transactions on Biomedical Engineering.

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

[19]  G. Abadal,et al.  Electrochemical platinum coatings for improving performance of implantable microelectrode arrays. , 2002, Biomaterials.

[20]  Jack W. Judy,et al.  Multielectrode microprobes for deep-brain stimulation fabricated with a customizable 3-D electroplating process , 2005, IEEE Transactions on Biomedical Engineering.

[21]  W. Grill,et al.  Electrical properties of implant encapsulation tissue , 2006, Annals of Biomedical Engineering.

[22]  A. Branner,et al.  A multielectrode array for intrafascicular recording and stimulation in sciatic nerve of cats , 2000, Brain Research Bulletin.

[23]  Fabian Kloosterman,et al.  Recording and marking with silicon multichannel electrodes. , 2002, Brain research. Brain research protocols.

[24]  D. Kipke,et al.  Repeated voltage biasing improves unit recordings by reducing resistive tissue impedances , 2005, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[25]  J.P. Donoghue,et al.  Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex , 2005, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[26]  K. Djupsund,et al.  Flexible polyimide microelectrode array for in vivo recordings and current source density analysis. , 2007, Biosensors & bioelectronics.

[27]  R. Shepherd,et al.  Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study , 1997, Hearing Research.

[28]  C. McIntyre,et al.  Tissue and electrode capacitance reduce neural activation volumes during deep brain stimulation , 2005, Clinical Neurophysiology.

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

[30]  Wen-Hung Chao,et al.  Automatic spike sorting for extracellular electrophysiological recording using unsupervised single linkage clustering based on grey relational analysis , 2011, Journal of neural engineering.

[31]  Warren M. Grill,et al.  Selective Microstimulation of Central Nervous System Neurons , 2000, Annals of Biomedical Engineering.

[32]  David C. Martin,et al.  Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays , 2005, Experimental Neurology.

[33]  C B Maks,et al.  Deep brain stimulation activation volumes and their association with neurophysiological mapping and therapeutic outcomes , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[34]  Blaise Yvert,et al.  Nanostructuration strategies to enhance microelectrode array (MEA) performance for neuronal recording and stimulation , 2012, Journal of Physiology-Paris.

[35]  M. Bikson,et al.  Bio-heat transfer model of deep brain stimulation induced temperature changes. , 2006, Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference.

[36]  Chang-Soo Kim,et al.  Use of micromachined probes for the recording of cardiac electrograms in isolated heart tissues. , 2004, Biosensors & bioelectronics.

[37]  Fu-Shan Jaw,et al.  A laser micromachined probe for recording multiple field potentials in the thalamus , 2004, Journal of Neuroscience Methods.

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

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

[40]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[41]  J. Newman Current Distribution on a Rotating Disk below the Limiting Current , 1966 .

[42]  T. Aziz,et al.  Electron microscopy of tissue adherent to explanted electrodes in dystonia and Parkinson's disease. , 2004, Brain : a journal of neurology.

[43]  Warren M Grill,et al.  Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers , 2010, BMC urology.

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

[45]  Matthew D. Johnson,et al.  In vivo impedance spectroscopy of deep brain stimulation electrodes , 2009, Journal of neural engineering.

[46]  Justin C. Williams,et al.  Flexible polyimide-based intracortical electrode arrays with bioactive capability , 2001, IEEE Transactions on Biomedical Engineering.

[47]  F. Rattay Analysis of models for extracellular fiber stimulation , 1989, IEEE Transactions on Biomedical Engineering.

[48]  David C. Martin,et al.  Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film , 2006, Journal of neural engineering.

[49]  A. Lozano,et al.  Deep Brain Stimulation in Clinical Practice and in Animal Models , 2010, Clinical pharmacology and therapeutics.

[50]  Warren M. Grill,et al.  Prediction of myelinated nerve fiber stimulation thresholds: limitations of linear models , 2004, IEEE Transactions on Biomedical Engineering.

[51]  D.J. Anderson,et al.  Batch fabricated thin-film electrodes for stimulation of the central auditory system , 1989, IEEE Transactions on Biomedical Engineering.

[52]  C. McIntyre,et al.  Role of electrode design on the volume of tissue activated during deep brain stimulation , 2006, Journal of neural engineering.

[53]  D. Szarowski,et al.  Brain responses to micro-machined silicon devices , 2003, Brain Research.

[54]  Peter N Steinmetz,et al.  Assessing the direct effects of deep brain stimulation using embedded axon models , 2007, Journal of neural engineering.

[55]  M. Madou Fundamentals of microfabrication and nanotechnology , 2012 .

[56]  D. G. Herrera,et al.  Activation of c-fos in the brain , 1996, Progress in Neurobiology.

[57]  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.

[58]  K. Wise,et al.  A 16-channel CMOS neural stimulating array , 1992, 1992 IEEE International Solid-State Circuits Conference Digest of Technical Papers.

[59]  Xuefeng F. Wei,et al.  Current density distributions, field distributions and impedance analysis of segmented deep brain stimulation electrodes , 2005, Journal of neural engineering.

[60]  Christine Haberler,et al.  No tissue damage by chronic deep brain stimulation in Parkinson's disease , 2000, Annals of neurology.

[61]  Daryl R Kipke,et al.  Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants , 2007, Journal of neural engineering.

[62]  D. Durand,et al.  Modeling the effects of electric fields on nerve fibers: Determination of excitation thresholds , 1992, IEEE Transactions on Biomedical Engineering.

[63]  Warren M Grill,et al.  Impedance characteristics of deep brain stimulation electrodes in vitro and in vivo , 2009, Journal of neural engineering.

[64]  Charles D. Blaha,et al.  Mechanisms of Action of Deep Brain Stimulation , 2009 .

[65]  David C. Martin,et al.  A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex , 2005, Journal of neural engineering.

[66]  J. J. Fins Deep brain stimulation, deontology and duty: the moral obligation of non-abandonment at the neural interface , 2009, Journal of neural engineering.

[67]  J. Tarkington,et al.  Photically oriented conditioned reflexes elicited by electrical stimulation of the visual system in the cat. , 1973, Brain research.

[68]  K. Cheung Implantable microscale neural interfaces , 2007, Biomedical microdevices.

[69]  Thomas M. McKenna,et al.  Enabling Technologies for Cultured Neural Networks , 1994 .

[70]  Eduardo Fernández,et al.  Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve , 2004, IEEE Transactions on Biomedical Engineering.

[71]  Wamadeva Balachandran,et al.  Silicon-based microelectrodes for neurophysiology fabricated using a gold metallization/nitride passivation system , 1996 .

[72]  Daryl R. Kipke,et al.  Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes , 2006, IEEE Transactions on Biomedical Engineering.