Selective Microstimulation of Central Nervous System Neurons

AbstractThe goal of this study was to identify stimulus parameters and electrode geometries that were effective in selectively stimulating targeted neuronal populations within the central nervous system (CNS). Cable models of neurons that included an axon, initial segment, soma, and branching dendritic tree, with geometries and membrane dynamics derived from mammalian motoneurons, were used to study excitation with extracellular electrodes. The models reproduced a wide range of experimentally documented excitation patterns including current-distance and strength-duration relationships. Evaluation of different stimulus paradigms was performed using populations of fifty cells and fifty fibers of passage randomly positioned about an extracellular electrode(s). Monophasic cathodic or anodic stimuli enabled selective stimulation of fibers over cells or cells over fibers, respectively. However, when a symmetrical charge-balancing stimulus phase was incorporated, selectivity was greatly diminished. An anodic first, cathodic second asymmetrical biphasic stimulus enabled selective stimulation of fibers, while a cathodic first, anodic second asymmetrical biphasic stimulus enabled selective stimulation of cells. These novel waveforms provided enhanced selectivity while preserving charge balancing as is required to minimize the risk of electrode corrosion and tissue injury. Furthermore, the models developed in this study can predict the effectiveness of electrode geometries and stimulus parameters for selective activation of specific neuronal populations, and in turn represent useful tools for the design of electrodes and stimulus waveforms for use in CNS neural prosthetic devices. © 2000 Biomedical Engineering Society. PAC00: 8717Nn, 8719La, 8719Nn, 8717Aa

[1]  J. B. Ranck,et al.  THE SPECIFIC IMPEDANCE OF THE DORSAL COLUMNS OF CAT: AN INISOTROPIC MEDIUM. , 1965, Experimental neurology.

[2]  E Jankowska,et al.  Direct and indirect activation of nerve cells by electrical pulses applied extracellularly. , 1976, The Journal of physiology.

[3]  B. Gustafsson,et al.  An investigation of threshold properties among cat spinal alpha‐motoneurones. , 1984, The Journal of physiology.

[4]  William F. Agnew,et al.  Micturition control by microstimulation of the sacral spinal cord of the cat: acute studies , 1995 .

[5]  Michael J. O'Donovan,et al.  Tapping into spinal circuits to restore motor function , 1999, Brain Research Reviews.

[6]  C. McIntyre,et al.  Excitation of central nervous system neurons by nonuniform electric fields. , 1999, Biophysical journal.

[7]  W. Vogel,et al.  Uneven distribution of K+ channels in soma, axon and dendrites of rat spinal neurones: functional role of the soma in generation of action potentials , 1998, The Journal of physiology.

[8]  H. Lüscher,et al.  Passive electrical properties of ventral horn neurons in rat spinal cord slices. , 1998, Journal of neurophysiology.

[9]  W. Crill,et al.  Specific membrane properties of cat motoneurones , 1974, The Journal of physiology.

[10]  J Nilsson,et al.  The time constants of motor and sensory peripheral nerve fibers measured with the method of latent addition. , 1994, Electroencephalography and clinical neurophysiology.

[11]  W. D. Thompson,et al.  Excitation of pyramidal tract cells by intracortical microstimulation: effective extent of stimulating current. , 1968, Journal of neurophysiology.

[12]  R. Lipowsky,et al.  Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells. , 1996, Journal of neurophysiology.

[13]  P Bawa,et al.  Computer simulation of the responses of human motoneurons to composite 1A EPSPS: effects of background firing rate. , 1997, Journal of neurophysiology.

[14]  W. Crill,et al.  Voltage clamp of cat motoneurone somata: properties of the fast inward current. , 1980, The Journal of physiology.

[15]  J. Munson,et al.  Membrane electrical properties and prediction of motor-unit type of medial gastrocnemius motoneurons in the cat. , 1985, Journal of neurophysiology.

[16]  Warren M. Grill,et al.  Stimulus waveforms for selective neural stimulation , 1995 .

[17]  W. Roberts,et al.  Analysis of threshold currents during microstimulation of fibres in the spinal cord. , 1973, Acta physiologica Scandinavica.

[18]  G. A. Robinson,et al.  Adaptation of cat motoneurons to sustained and intermittent extracellular activation. , 1993, The Journal of physiology.

[19]  N T Carnevale,et al.  Electrotonic architecture of hippocampal CA1 pyramidal neurons based on three-dimensional reconstructions. , 1996, Journal of neurophysiology.

[20]  M. Rydmark,et al.  Dimensions of individual alpha and gamma motor fibres in the ventral funiculus of the cat spinal cord. , 1994, Journal of anatomy.

[21]  W. Grill,et al.  Modeling the effects of electric fields on nerve fibers: influence of tissue electrical properties , 1999, IEEE Transactions on Biomedical Engineering.

[22]  Jean Bullier,et al.  Spread of stimulating current in the cortical grey matter of rat visual cortex studied on a new in vitro slice preparation , 1996, Journal of Neuroscience Methods.

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

[24]  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.

[25]  J. Fleshman,et al.  Rheobase, input resistance, and motor-unit type in medial gastrocnemius motoneurons in the cat. , 1981, Journal of neurophysiology.

[26]  C. Kufta,et al.  Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex , 1996 .

[27]  S. Cullheim,et al.  A morphological study of the axons and recurrent axon collaterals of cat alpha‐motoneurones supplying different hind‐limb muscles. , 1978, The Journal of physiology.

[28]  J. Clements,et al.  Cable properties of cat spinal motoneurones measured by combining voltage clamp, current clamp and intracellular staining. , 1989, The Journal of physiology.

[29]  Warren M. Grill,et al.  Bladder and urethral pressures evoked by microstimulation of the sacral spinal cord in cats , 1999, Brain Research.

[30]  C.C. McIntyre,et al.  Model-based design of stimulus waveforms for selective microstimulation in the central nervous system , 1999, Proceedings of the First Joint BMES/EMBS Conference. 1999 IEEE Engineering in Medicine and Biology 21st Annual Conference and the 1999 Annual Fall Meeting of the Biomedical Engineering Society (Cat. N.

[31]  D. Johnston,et al.  Axonal Action-Potential Initiation and Na+ Channel Densities in the Soma and Axon Initial Segment of Subicular Pyramidal Neurons , 1996, The Journal of Neuroscience.

[32]  F. Rattay,et al.  Analysis of the electrical excitation of CNS neurons , 1998, IEEE Transactions on Biomedical Engineering.

[33]  T. Velte,et al.  A computational model of electrical stimulation of the retinal ganglion cell , 1999, IEEE Transactions on Biomedical Engineering.

[34]  D. McCreery,et al.  Stimulation with chronically implanted microelectrodes in the cochlear nucleus of the cat: Histologic and physiologic effects , 1992, Hearing Research.

[35]  R. Burke,et al.  Membrane area and dendritic structure in type‐identified triceps surae alpha motoneurons , 1987, The Journal of comparative neurology.

[36]  J T AITKEN,et al.  Neuron size and neuron population density in the lumbosacral region of the cat's spinal cord. , 1961, Journal of anatomy.

[37]  W. Catterall,et al.  Localization of sodium channels in axon hillocks and initial segments of retinal ganglion cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[38]  W. Vogel,et al.  Functional Distribution of Three Types of Na+ Channel on Soma and Processes of Dorsal Horn Neurones of Rat Spinal Cord , 1997, The Journal of physiology.

[39]  Hugh Bostock,et al.  Action potentials and membrane currents in the human node of Ranvier , 1995, Pflügers Archiv.

[40]  J. Carp,et al.  Physiological properties of primate lumbar motoneurons. , 1992, Journal of neurophysiology.

[41]  I Segev,et al.  Electrotonic architecture of type-identified alpha-motoneurons in the cat spinal cord. , 1988, Journal of neurophysiology.

[42]  W. Crill,et al.  Voltage‐sensitive outward currents in cat motoneurones. , 1980, The Journal of physiology.

[43]  L A Bullara,et al.  Electrical stimulation of the brain. III. The neural damage model. , 1975, Surgical neurology.

[44]  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.

[45]  C. Kufta,et al.  Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex. , 1996, Brain : a journal of neurology.

[46]  Warren M. Grill,et al.  Sensitivity analysis of a model of mammalian neural membrane , 1998, Biological Cybernetics.

[47]  J. R. Hughes,et al.  Brief, noninjurious electric waveform for stimulation of the brain. , 1955, Science.

[48]  M. Larkum,et al.  Propagation of action potentials in the dendrites of neurons from rat spinal cord slice cultures. , 1996, Journal of neurophysiology.

[49]  M. H. Evans,et al.  Measurement of current spread from microelectrodes when stimulating within the nervous system , 1976, Experimental Brain Research.

[50]  D. Durand The somatic shunt cable model for neurons. , 1984, Biophysical journal.

[51]  S L BeMent,et al.  A quantitative study of electrical stimulation of central myelinated fibers. , 1969, Experimental neurology.

[52]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[53]  H. Clamann,et al.  The relation between size of motoneurons and their position in the cat spinal cord , 1977, Journal of morphology.

[54]  J T Rubinstein,et al.  Threshold fluctuations in an N sodium channel model of the node of Ranvier. , 1995, Biophysical journal.