Biomedical subjects

W M Grill

Publications and source records attributed to W M Grill.

At least 19 recordsLinked to original sources

PubMed2001

Optimal filtering of whole nerve signals.

Electroneurographic recordings suffer from low signal to noise (S/N) ratios. The S/N ratio can be improved by different signal processing methods including optimal filtering. A method to design two types of optimal filters (Wiener and Matched filters) was developed for use with neurographic signals, and the calculated filters were applied to nerve cuff recordings from the cat S1 spinal root that were recorded during the activation of cutaneous, bladder, and rectal mechanoreceptors. The S1 spinal root recordings were also filtered using various band-pass (BP) filters with different cut-off frequencies, since the frequency responses of the Wiener and Matched filters had a band-pass character. The mean increase in the S/N ratio across all recordings was 54, 89, and 85% for the selected best Wiener, Matched, and band-pass filters, respectively. There were no statistically significant differences between the performance of the selected filters when all three methods were compared. However, Matched filters yielded a greater increase in S/N ratio than Wiener filters when only two filtering techniques were compared. All three filtering methods have in most cases also improved the selectivity of the recordings for different sensory modalities. This might be important when recording nerve activity from a mixed nerve innervating multiple end-organs to increase the modality selectivity for the nerve fibers of interest. The mean Modality Selectivity Indices (MSI) over different receptor types and for the same selected filters as above were 1.12, 1.27, and 1.29, respectively, and indicate increases in modality selectivity (MSI>1). Improving the S/N ratio and modality selectivity of neurographic recordings is an important development to increase the utility of neural signals for understanding neural function and for use as feedback or control signals in neural prosthetic devices.

Action Potentials↗

PubMed2001

Detection and inhibition of hyperreflexia-like bladder contractions in the cat by sacral nerve root recording and electrical stimulation.

Detection of bladder volume and hyperreflexive bladder contractions would be useful in individuals with overactive bladders. We sought to determine whether bladder filling and/or reflex bladder contractions could be detected by electrical recording from the sacral nerve roots, and whether bladder contractions could be inhibited by stimulation of sacral afferents. Six male cats were anesthetized with alpha-chloralose and bipolar cuff electrodes were used to measure sacral nerve root electroneurograms (ENG) during slow bladder filling, during rapid injections of fluid into the bladder, and during hyperreflexia-like bladder contractions. The rectified and time-averaged activity of the S1 extradural root increased by 0-5 % above the baseline during bladder filling. Rapid injections caused a sudden increase in bladder pressure, and a 3-36 % increase over baseline in the S1 nerve activity. Withdrawal of the same volume caused a reduction in pressure and a decrease in recorded activity (4-14 %). At the onset of a bladder contraction, there was a 7-38 % increase over baseline in the S1 nerve activity. This activity increase was sustained for the duration of the contraction and decreased during bladder relaxation. The onset and duration of bladder contractions could be detected consistently from these nerve activity changes. Recording only afferent activity showed that the increased nerve activity was due to S1 sensory rather than motor fibers. In two cats, it was demonstrated that an ongoing bladder contraction could be inhibited by rectal distension. In one cat, the contractions could be terminated by electrical stimulation of the S1 dorsal root. The results demonstrate that afferent sacral root nerve activity can be used to detect hyperreflexive bladder contractions at low bladder pressures. Such a signal might be used to trigger bladder inhibition via electrical stimulation of specific sacral afferents.

Animals↗

PubMed2001

Finite element analysis of the current-density and electric field generated by metal microelectrodes.

Electrical stimulation via implanted microelectrodes permits excitation of small, highly localized populations of neurons, and allows access to features of neuronal organization that are not accessible with larger electrodes implanted on the surface of the brain or spinal cord. As a result there are a wide range of potential applications for the use of microelectrodes in neural engineering. However, little is known about the current-density and electric field generated by microelectrodes. The objectives of this project were to answer three fundamental questions regarding electrical stimulation with metal microelectrodes using geometrically and electrically accurate finite elements models. First, what is the spatial distribution of the current density over the surface of the electrode? Second, how do alterations in the electrode geometry effect neural excitation? Third, under what conditions can an electrode of finite size be modeled as a point source? Analysis of the models showed that the current density was concentrated at the tip of the microelectrode and at the electrode-insulation interface. Changing the surface area of the electrode, radius of curvature of the electrode tip, or applying a resistive coating to the electrode surface altered the current-density distribution on the surface of the electrode. Changes in the electrode geometry had little effect on neural excitation patterns, and modeling the electric field generated by sharply tipped microelectrodes using a theoretical point source was valid for distances > approximately 50 microm from the electrode tip. The results of this study suggest that a nearly uniform current-density distribution along the surface of the electrode can be achieved using a relatively large surface area electrode (500-1000 microm2), with a relatively blunt tip (3-6 microm radius of curvature), in combination with a thin (approximately 1 microm) moderately resistive coating (approximately 50 omega m).

Biocompatible Materials↗

PubMed2001

Neural network classification of nerve activity recorded in a mixed nerve.

Whole-nerve cuff electrodes can be used to record electrical nerve activity in peripheral nerves and are suitable for chronic implantation in animals or humans. If the whole nerve innervates multiple target organs or muscles then the recorded activity will be the superposition of the activity of different nerve fibers innervating these organs. In certain cases it is desirable to monitor mixed nerve activity and to determine the origin (modality) of the recorded activity. A method using the autocorrelation function of recorded nerve activity and an artificial neural network was developed to classify the modality of nerve signals. The method works in cases where different end organs are innervated by nerve fibers having different diameter distributions. The electrical activity in the cat S1 sacral spinal root was recorded using a cuff electrode during the activation of cutaneous, bladder, and rectal mechanoreceptors. Using the classification method, 87.5% of nerve signals were correctly classified. This result demonstrates the effectiveness of the neural network classification method to determine the modality of the nerve activity arising from activation of different receptors.

Action Potentials↗

PubMed2000

Neural and connective tissue response to long-term implantation of multiple contact nerve cuff electrodes.

The objective of this study was to characterize the tissue response to multiple contact spiral nerve cuff electrodes implanted on the sciatic nerve of seven cats for 28-34 weeks. The cuffs were surrounded by fibrous tissue encapsulation consisting of foreign body cells, collagen, and fibroblasts. Focal areas of abnormal neural morphology including perineurial thickening, endoneurial fibrosis, thinly myelinated axons, and focal reduction in the density of myelinated axons were noted in five of seven nerves. In three implants, the percutaneous lead cable was destroyed by the animal pulling on the external leads. Morphological changes were observed in two of three nerves from implants sustaining no known animal induced trauma (group A), and in three of four nerves from implants damaged by the animal pulling at the leads (group B). All nerves appeared normal 2 cm proximal to the cuff. At the cuff level, small regions of one fascicle in each of two nerves (both group B) exhibited abnormalities, while the proximal and distal sections of both nerves were normal. Distal to the cuff, small regions of seven fascicles distributed among three nerves (two group A, one group B) exhibited abnormalities. These nerves were normal at the cuff level but exhibited abnormalities in individual nerve branches distal to the cuff. The incidence and characteristics of the morphological abnormalities at the cuff level are consistent with those observed in previous studies of nerve cuff electrodes, and support the hypothesis that spiral cuff electrodes can be implanted with an internal diameter less than that of the nerve and expand to accommodate the nerve without compression The pattern of morphological abnormalities indicated that mechanical trauma had occurred at some time in the past, and the distribution suggested animal intervention and the lead cable as possible causes.

Animals↗

PubMed2000

Modelling the effects of electric fields on nerve fibres: influence of the myelin sheath.

The excitation and conduction properties of computer-based cable models of mammalian motor nerve fibres, incorporating three different myelin representations, are compared. The three myelin representations are a perfectly insulating single cable (model A), a finite impedance single cable (model B) and a finite impedance double cable (model C). Extracellular stimulation of the three models is used to study their strength-duration and current-distance (I-X) relationships, conduction velocity (CV) and action potential shape. All three models have a chronaxie time that is within the experimental range. Models B and C have increased threshold currents compared with model A, but each model has slope to the I-X relationship that matches experimental results. Model B has a CV that matches experimental data, whereas the CV of models A and C are above and below the experimental range, respectively. Model C is able to produce a depolarising afterpotential (DAP), whereas models A and B exhibit hyperpolarising afterpotentials. Models A and B are determined to be the preferred models when low-frequency stimulation (< approximately 25 Hz) is used, owing to their efficiency and accurate excitation and conduction properties. For high frequency stimulation (approximately 25 Hz and greater), model C, with its ability to produce a DAP, is necessary accurately to simulate excitation behaviour.

Animals↗

PubMed2000

Neuroprosthetic applications of electrical stimulation.

Neural prostheses are a developing technology that use electrical activation of the nervous system to restore function to individuals with neurological impairment. Neural prostheses function by electrical initiation of action potentials in nerve fibers that carry the signal to an endpoint where chemical neurotransmitters are released, either to affect an end organ or another neuron. Thus, in principle, any end organ under neural control is a candidate for neural prosthetic control. Applications have included stimulation in both the sensory and motor systems and range in scope from experimental trials with single individuals to commercially available devices. Outcomes of motor system neural prostheses include restoration of hand grasp and release in quadriplegia, restoration of standing and stepping in paraplegia, restoration of bladder function (continence, micturition) following spinal cord injury, and electrophrenic respiration in high-level quadriplegia. Neural prostheses restore function and provide greater independence to individuals with disability.

Bionics↗

PubMed2000

Selective microstimulation of central nervous system neurons.

The 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.

Animals↗

PubMed1999

Bladder and urethral pressures evoked by microstimulation of the sacral spinal cord in cats.

Experiments were conducted to measure the bladder and urethral pressures evoked by intraspinal microstimulation of the sacral segments (S1-S2) in neurologically intact, chloralose anesthetized adult male cats. The bladder pressure was measured with a superpubic catheter and the urethral pressure was measured simultaneously at the level of the urethral sphincter and at the level of the penis using a two-element micromanometer. Intraspinal stimuli (typically 1 s, 20 Hz, 100 microA, 100 microseconds) were applied with activated iridium microwire electrodes in ipsilateral segments and intersegmental boundaries with a 250 micrometer mediolateral resolution and a 200 micrometer dorsoventral resolution. Increases in bladder pressures were generated by microstimulation in the intermediolateral region, in the lateral and ventrolateral ventral horn, and around the central canal. Simultaneous increases in urethral pressure were evoked by microstimulation in the ventrolateral ventral horn, but not at the other locations. Small reductions in urethral pressure (<10 cm H(2)O) were evoked at locations in the intermediate laminae and around the central canal. The magnitude of these pressure reductions was weakly dependent on the stimulus parameters. Stimulation around the central canal produced bladder contractions with either no change or a reduction in urethral pressure and voiding of small amounts of fluid. These results demonstrate that regions are present in the spinal intact anesthetized cat where microstimulation generates selective contraction of the bladder without increases in urethral pressure and that regions are present where microstimulation generates small reductions in urethral pressure.

Animals↗

PubMed1999

Extended survival time following pseudorabies virus injection labels the suprapontine neural network controlling the bladder and urethra in the rat.

The central neurons that are involved in control of the urinary bladder and proximal urethra in adult male rats were identified by retrograde transport of the viral transneural tracer pseudorabies virus (PRV, Bartha strain). At 5 days post-injection, PRV-infected neurons were found in suprapontine central nervous system nuclei including ventrolateral periaqueductal gray, magnocellular division of the red nucleus, lateral hypothalamus and paraventricular nucleus, retrochiasmic region and suprachiasmatic nucleus. At days 6 and 7 PRV-infected neurons were observed in the amygdala, lateral septal nucleus, hippocampus, and frontal motor, piriform, and perirhinal cortices. These results identify the supraspinal neural networks that are involved in control of the lower urinary tract, and demonstrate the utility of long survival times to label higher-order neurons with PRV.

Animals↗

PubMed1999

Excitation of central nervous system neurons by nonuniform electric fields.

The goal of this study was to determine which neural elements are excited by microstimulation of the central nervous system. A cable model of a neuron including an axon, initial segment, axon hillock, soma, and simplified dendritic tree was used to study excitation with an extracellular point source electrode. The model reproduced a wide range of experimentally documented extracellular excitation patterns. The site of action potential initiation (API) was a function of the electrode position, stimulus duration, and stimulus polarity. The axon or initial segment was always the site of API at threshold. When the electrode was positioned near the cell body, the site of excitation was dependent on the stimulus amplitude. With the electrode in close proximity to the neuron, short-duration cathodic pulses produced lower thresholds with the electrode positioned over the axon than over the cell body, and long-duration stimuli produced opposite relative thresholds. This result was robust to alterations in either the maximum conductances or the intracellular resistivities of the model. The site of maximum depolarization was not always an accurate predictor of the site of API, and the temporal evolution of the changes in membrane potential played a strong role in determining the site of excitation.

Action Potentials↗

PubMed1999

Tapping into spinal circuits to restore motor function.

Motivated by the challenge of improving neuroprosthetic devices, the authors review current knowledge relating to harnessing the potential of spinal neural circuits, such as reflexes and pattern generators. If such spinal interneuronal circuits could be activated, they could provide the coordinated control of many muscles that is so complex to implement with a device that aims to address each participating muscle individually. The authors' goal is to identify candidate spinal circuits and areas of research that might open opportunities to effect control of human limbs through electrical activation of such circuits. David McCrea's discussion of the ways in which hindlimb reflexes in the cat modify motor activity may help in developing optimal strategies for functional neuromuscular stimulation (FNS), by using knowledge of how reflex actions can adapt to different conditions. Michael O'Donovan's discussion of the development of rhythmogenic networks in the chick embryo may provide clues to methods of generating rhythmic activity in the adult spinal cord. Serge Rossignol examines the spinal pattern generator for locomotion in cats, its trigger mechanisms, modulation and adaptation, and suggests how this knowledge can help guide therapeutic approaches in humans. Hugues Barbeau applies the work of Rossignol and others to locomotor training in human subjects who have suffered spinal cord injury (SCI) with incomplete motor function loss (IMFL). Michel Lemay and Warren Grill discuss some of the technical challenges that must be addressed by engineers to implement a neuroprosthesis using electrical stimulation of the spinal cord, particularly the control issues that would have to be resolved.

Adaptation, Physiological↗

PubMed1999

Modeling the effects of electric fields on nerve fibers: influence of tissue electrical properties.

The effects of anisotropy and inhomogeneity of the electrical conductivity of extracellular tissue on excitation of nerve fibers by an extracellular point source electrode were determined by computer simulation. Analytical solutions to Poison's equation were used to calculate potentials in anisotropic infinite homogeneous media and isotropic semi-infinite inhomogeneous media, and the net driving function was used to calculate excitation thresholds for nerve fibers. The slope and intercept of the current-distance curve in anisotropic media were power functions of the ratio and product of the orthogonal conductivities, respectively. Excitation thresholds in anisotropic media were also dependent on the orientation of the fibers, and in strongly anisotropic media (sigma z/sigma xy > 4) there were reversals in the recruitment order between different diameter fibers and between fibers at different distances from the electrode. In source-free regions of inhomogeneous media (two regions of differing conductivity separated by a plane boundary), the current-distance relationship of fibers parallel to the interface was dependent only on the average conductivity, whereas in regions containing the source the current-distance relationship was dependent on the individual values of conductivity. Reversals in recruitment order between fibers at different distances from the electrode and between fibers of differing diameter were found in inhomogeneous media. The results of this simulation study demonstrate that the electrical properties of the extracellular medium can have a strong influence on the pattern of neuronal excitation generated by extracellular electric fields, and indicate the importance of tissue electrical properties in interpreting results of studies employing electrical stimulation applied in complex biological volume conductors.

Anisotropy↗

PubMed1999

Functional anatomy of the male feline urethra: morphological and physiological correlations.

Anatomical and histological methods were combined with measurements of the urethral pressure profile (UPP) to investigate the functional aspects of the urethra in male cats. A silicone rubber catheter with two microdiaphragm pressure transducers was used to measure the UPP. Gross anatomy and ultrastructure of the urethra at each segment were examined and correlated with the pressure profile data. The preprostatic urethra was composed of three layers of smooth muscle, while distal to the prostate striated muscle became predominant. Increased baseline pressure and rapid fluctuations in pressure in the postprostatic urethra and bulbourethra resulted from the function of periurethral striated musculature. The UPP was affected by the bladder pressure, repetition of the measurement, the sensor orientation in the urethra, and the type of measurement catheter. Well controlled high fidelity measurements enabled a clear correlation to be established between the features of the UPP and the anatomy of the urethra and surrounding musculature. Additionally, observations on the ultrastructural and microscopic anatomy of the urethra extend a previous description of the pelvic urethra.

Animals↗

PubMed1998

Identification of the spinal neural network involved in coordination of micturition in the male cat.

In these studies, we used the expression of Fos protein to identify cells within the spinal cord that regulate micturition in male cats. The immediate early gene c-fos that encodes the Fos protein can be induced rapidly and transiently in neurons by increased electrical activity. Animals were anesthetized with alpha-chloralose, and received one of four stimulus protocols: electrical stimulation of the pelvic nerve, electrical stimulation of the pudendal nerve, a period of isometric micturition (induced by ligating the proximal urethra and infusing saline into the bladder), or electrical stimulation of Barrington's nucleus. After the period of stimulation, the animals were perfused and neurons expressing Fos-like immunoreactivity (FLI) were visualized with immunocytochemical methods. Stimulation with each protocol resulted in a substantially larger number of neurons expressing FLI than in operated but unstimulated controls, which exhibited few Fos-positive neurons localized to the superficial dorsal horn. In animals undergoing isometric micturition or stimulation of Barrington's nucleus, neurons exhibiting FLI were found bilaterally in the sacral (S1-S3) spinal cord and were localized to the lateral portion of the superficial dorsal horn (laminae I and II), in the intermediolateral region (lateral laminae V-VII), and around the central canal (lamina X and medial laminae V-VII). The intermediolateral region appeared to contain two populations of cells exhibiting FLI: a group of large multipolar cells and a group of small round cells. Few Fos-immunoreactive nuclei were observed in the medial portion of the superficial dorsal horn, and FLI was not observed in ventral horn neurons. Electrical stimulation of the pudendal or pelvic nerves resulted in fewer numbers of cells exhibiting FLI, with a less widespread spatial distribution. These results identify spinal neurons that are active during the micturition cycle, and demonstrate that a behaviorally relevant stimulus (isometric micturition) generated more widespread and greater intensity of Fos expression than repetitive electrical stimulation of the component peripheral nerves.

Animals↗

PubMed1998

Sensitivity analysis of a model of mammalian neural membrane.

The sensitivity of the strength-duration (S-D) relationship to changes in the parameters describing the sodium channel of mammalian neuronal membrane was determined by computer simulation. A space-clamped patch of neuronal membrane was modeled by a parallel nonlinear sodium conductance, linear leakage conductance, and membrane capacitance. Each parameter that governs the activation (m) and inactivation (h) variables of the sodium channel was varied from -50% to +50% of its default value, and for each variation a S-D relationship was generated. Individual changes in six of the eleven parameters (alpha mA, alpha mD, alpha hA, beta mA, beta mB, and beta hB) generated substantial changes in the rheobase current and chronaxie time (Tch) of the model. Changing the parameter values individually did not correct for the model's failure to generate excitation after the release from a long duration hyperpolarization (anode break excitation). Scaling a combination of five parameters (alpha mA, alpha mB, alpha hA, beta mA, and beta hB) by an equal amount produced a model that generated anode break excitation and increased Tch, but also decreased the amplitude of the action potential. To reproduce the amplitude of the action potential, the maximum sodium conductance and sodium Nernst potential were increased. These modifications generated a model that had S-D properties closer to experimental results, could produce anode break excitation, and reproduced the action potential amplitude.

Action Potentials↗

PubMed1998

Stability of the input-output properties of chronically implanted multiple contact nerve cuff stimulating electrodes.

The objective of this investigation was to measure the input-output (I-O) properties of chronically implanted nerve cuff electrodes. Silicone rubber spiral nerve cuff electrodes, containing 12 individual platinum electrode contacts, were implanted on the sciatic nerve of seven adult cats for 28-34 weeks. Measurements of the torque generated at the ankle joint by electrical stimulation of the sciatic nerve were made every 1-2 weeks for the first 6 weeks post-implant and every 3-5 weeks between 6 weeks and 32 weeks post-implant. In three implants the percutaneous lead cable was irreparably damaged by the animal within 4 weeks after implant and further testing was not possible. One additional lead cable was irreparably damaged by the animal at 17 weeks post-implant. The three remaining implants functioned for 28, 31, and 32 weeks. Input-output curves of ankle joint torque as a function of stimulus current amplitude were repeatable within an experimental session, but there were changes in I-O curves between sessions. The degree of variability in I-O properties differed between implants and between different contacts within the same implant. After 8 weeks, the session to session changes in the stimulus amplitude required to generate 50% of the maximum torque (I50) were smaller (15+/-19%, mean +/- s.d.) than the changes in I50 measured between 1 week and 8 weeks post-implant (34+/-42%). Furthermore, the I-O properties were more stable across changes in limb position in the late post-implant period than in acutely implanted cuff electrodes. These results suggest that tissue encapsulation acted to stabilize chronically implanted cuff electrodes. Electrode movement relative to the nerve, de- and regeneration of nerve fibers, and the inability to precisely reproduce limb position in the measurement apparatus all may have contributed to the variability in I-O properties.

Animals↗

PubMed1997

Inversion of the current-distance relationship by transient depolarization.

The objective of this research was to develop a technique to excite selectively nerve fibers distant from an electrode without exciting nerve fibers close to the electrode. The shape of the stimulus current waveform was designed based on the nonlinear conductance properties of neuronal sodium channel. Models of mammalian peripheral myelinated axons and experimental measurements on cat sciatic nerve were used to determine the effects of subthreshold polarization on neural excitability and recruitment. Subthreshold membrane depolarization generated a transient decrease in neural excitability and thus an increase in the threshold for stimulation by a subsequent stimulus pulse. The decrease in excitability increased as the duration and amplitude of the subthreshold depolarization were increased, and the increase in threshold was greater for fibers close to the electrode. When a depolarizing stimulus pulse was applied immediately after the subthreshold depolarization, nerve fibers far from the electrode could be stimulated without stimulating fibers close to the electrode. Subthreshold depolarizing prepulses inverted the current-distance relationship and allowed selective stimulation of nerve fibers far from the electrode.

Animals↗