Discharge properties of identified cochlear nucleus neurons and auditory nerve fibers in response to repetitive electrical stimulation of the auditory nerve

Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29°C, we intracellularly recorded and stained cochlear nucleus (CN) neurons and auditory nerve (AN) fibers. Discharge properties of CN cells and AN axons were tested in response to 50-ms trains of electrical pulses delivered to the AN at rates ranging from 100 to 1000 pulses per second (pps). At low stimulation rates (200–300 pps), the discharges of AN fibers and a large proportion of principal cells (bushy, octopus, stellate) in the ventral cochlear nucleus (VCN) followed with high probability each pulse in the train, resulting in synchronization of discharges within large populations of AN fibers and CN cells. In contrast, at high stimulation rates (500 pps and higher), AN fibers and many VCN cells exhibited "primary-like", "onset" and some other discharge patterns resembling those produced by natural sound stimuli. Unlike cells in the VCN, principal cells (pyramidal, giant) of the dorsal CN did not follow the stimulating pulses even at low rates. Instead, they often showed "pauser" and "build-up" patterns of activity, characteristic for these cells in conditions of normal hearing. We hypothesize that, at low stimulation rates, the response behavior of AN fibers and VCN cells is different from the patterns of neuronal activity related to normal auditory processing, whereas high stimulation rates produce more physiologically meaningful discharge patterns. The observed differences in discharge properties of AN fibers and CN cells at different stimulation rates can contribute to significant advantages of high- versus low-rate electrical stimulation of the AN used for coding sounds in modern cochlear implants.     

Neural modeling in electrical stimulation

In general, complete mathematical modeling of electrical neurostimulation encompasses two separate problems; clear delineation of this article becomes important. Solutions are required for the time-varying macroscopic fields generated by the stimulating electrodes, and only then can biophysical analysis be brought to bear on neural structures within those fields. This article is focused on the second of these aspects, and provides a survey of mathematical representations including nerve cell bodies, myelinated and unmyelinated fibers of passage, branched systems, fiber terminals and composite neurons. Effects on nerve cells of fields generated by remote electrodes are given primary attention, although methods for obtaining field solutions in biological media are discussed in detail only where the issue is inextricably linked to the use of a particular neural model, or relates crucially to experimental validation. Within these guidelines, it is intended to show the significant role that current nerve cell models may play in attempts to understand mechanisms of neural stimulation, and in the development of more advanced strategies for electronic intervention and control of neural function.     

Response of inferior colliculus neurons to electrical stimulation of the auditory nerve in neonatally deafened cats.

Response properties of neurons in the inferior colliculus (IC) were examined in control and profoundly deafened animals to electrical stimulation of the auditory nerve. Seven adult cats were used: two controls; four neonatally deafened (2 bilaterally, 2 unilaterally); and one long-term bilaterally deaf cat. All control cochleae were deafened immediately before recording to avoid electrophonic activation of hair cells. Histological analysis of neonatally deafened cochleae showed no evidence of hair cells and a moderate to severe spiral ganglion cell loss, whereas the long-term deaf animal had only 1-2% ganglion cell survival. Under barbiturate anesthesia, scala tympani electrodes were implanted bilaterally and the auditory nerve electrically stimulated using 100 micros/phase biphasic current pulses. Single-unit (n = 419) recordings were made through the lateral (LN) and central (ICC) nuclei of the IC; responses could be elicited readily in all animals. Approximately 80% of cells responded to contralateral stimulation, whereas nearly 75% showed an excitatory response to ipsilateral stimulation. Most units showed a monotonic increase in spike probability and reduction in latency and jitter with increasing current. Nonmonotonic activity was seen in 15% of units regardless of hearing status. Neurons in the LN exhibited longer latencies (10-25 ms) compared with those in the ICC (5-8 ms). There was a deafness-induced increase in latency, jitter, and dynamic range; the extent of these changes was related to duration of deafness. The ICC maintained a rudimentary cochleotopic organization in all neonatally deafened animals, suggesting that this organization is laid down during development in the absence of normal afferent input. Temporal resolution of IC neurons was reduced significantly in neonatal bilaterally deafened animals compared with acutely deafened controls, whereas neonatal unilaterally deafened animals showed no reduction. It would appear that monaural afferent input is sufficient to maintain normal levels of temporal resolution in auditory midbrain neurons. These experiments have shown that many of the basic response properties are similar across animals with a wide range of auditory experience. However, important differences were identified, including increased response latencies and temporal jitter, and reduced levels of temporal resolution.     

Effect of electrical stimulation of the crossed olivocochlear bundle on auditory nerve response to tones in noise

The discharge rates of single auditory-nerve fibers responding to best-frequency (BF) tones of varying level presented simultaneously with fixed level broadband noise were recorded with and without electrical stimulation of the crossed olivocochlear bundle (COCB). In the absence of COCB stimulation, monotonic increases in noise level produce monotonic increases in the low-level noise-driven response rate of auditory nerve fibers. As a result of adaptation, these increases in noise-driven response rate produce monotonic decreases in saturation discharge rate. At high noise levels, these compressive effects may eliminate the differential rate response of auditory nerve fibers to BF tones. COCB stimulation can restore this differential rate response by producing large decreases in noise-driven response rate and large increases in saturation discharge rate. In backgrounds of quiet, COCB stimulation is known to shift the dynamic range of single auditory nerve fiber BF tone responses to higher stimulus levels. In the presence of background noise, COCB stimulation produces upward shift of dynamic range, which decreases with increasing noise level. At high noise levels, COCB-induced decompression of rate-level functions may occur with little or no dynamic range shift. This enables auditory nerve fibers to signal changes in tone level with changes in discharge rate at lower signal-to-noise ratios than would be possible otherwise. Broadband noise also produces upward shift of the dynamic range of single auditory nerve fiber BF tone response. Noise-induced dynamic range shift of BF tone response was measured as a function of noise level with and without COCB stimulation. COCB stimulation elevates the threshold of noise-induced dynamic range shift. This shift is thought to result from two-tone rate suppression. Increases in the threshold of noise-induced shift due to COCB stimulation therefore suggests an interaction between the mechanism of two-tone rate suppression and the mechanism by which COCB stimulation produces dynamic range shift. These interactions were further investigated by recording auditory nerve fiber rate responses to fixed-level BF excitor tones presented simultaneously with fixed-frequency variable level suppressor tones. Rate responses were recorded with and without COCB stimulation. Experimental results were quantified using a phenomenological model of two-tone rate suppression presented by Sachs and Abbas.     

Simulation of intra-orbital optic nerve electrical stimulation

In blind subjects who still have functional retinal ganglion cells, electrical stimuli applied to the optic nerve can produce localised visual sensations. This has been demonstrated with an intracranially implanted self-sizing spiral cuff electrode, but, to avoid skull opening, intra-orbital cuff implantation is now considered. In its orbital segment, the optic nerve is surrounded by subarachnoidal cerebrospinal fluid (CSF) and dura mater. Dura mater is a tough fibrous tissue that can impede electrical stimulation. In the study, the issue of whether or not to remove the dura mater at the implantation site was addressed using simulation on numerical models. Several volume conductor models were built representing, respectively: the cuff implanted directly around the nerve; the cuff over the nerve after connective tissue encapsulated the implant; and the cuff electrode placed around the dura mater. Stimulation-induced electric potential fields were computed for these configurations using a full 3D finite elements software. Responses of fibres within the nerve were computed. A large range of dural conductivities and several CSF thicknesses were considered. In all simulated conditions, the presence of dura mater around a layer of CSF increased excitation thresholds. Selectivity performance also decreased, but was found to be independent of the CSF thickness. However, simulations showed that, if the diameter of the cuff electrode is adapted to the target nerve, the injected charge associated with activation is limited within a reasonable range. Electrical stimulation of the optic nerve with a cuff electrode implanted around the dura mater should therefore be feasible.     

Development of a model for point source electrical fibre bundle stimulation

A model is presented for determining the excitation (transmembrane) potentials on nerve and muscle fibres in a cylindrical bundle from an external point source electrode at the surface and within the preparation. The fibre bundle is considered to be immersed in an infinite isotropic conductive medium and is idealised as an infinitely extending cylinder. This cylinder is initially represented as an isotropic monodomain. A subsequent degree of complexity introduces anisotropy in the monodomain, and finally the bundle is represented as an anisotropic bidomain comprised of the interstitial radial and longitudinal conductivities, the intracellular longitudinal conductivity and the fibre membrane between the two domains. In this latter model, electrical coupling from extracellular to intracellular space is included by means of the bidomain formulation. Computational aspects are discussed, and preliminary results for prescribed conditions are presented.     

Asymptotic model of electrical stimulation of nerve fibers

We present a novel theory and computational algorithm for modeling electrical stimulation of nerve fibers in three dimensions. Our approach uses singular perturbation to separate the full 3D boundary value problem into a set of 2D “transverse” problems coupled with a 1D “longitudinal” problem. The resulting asymptotic model contains not one but two activating functions (AF): the longitudinal AF that drives the slow development of the mean transmembrane potential and the transverse AF that drives the rapid polarization of the fiber in the transverse direction. The asymptotic model is implemented for a prototype 3D cylindrical fiber with a passive membrane in an isotropic extracellular region. The validity of this approach is tested by comparing the numerical solution of the asymptotic model to the analytical solutions. The results show that the asymptotic model predicts steady-state transmembrane potential directly under the electrodes with the root mean square error of 0.539 mV, i.e., 1.04% of the maximum transmembrane potential. Thus, this work has created a computationally efficient algorithm that facilitates studies of the complete spatiotemporal dynamics of nerve fibers in three dimensions.     

Neuron discharges in the rat auditory cortex during electrical intracortical stimulation

Studies were carried out in rats anesthetized with ketamine or nembutal, with recording of multicellular activity (with separate identification of responses from individual neurons) in the primary auditory cortex before and after electrical intracortical microstimulation. These experiments showed that about half of the set of neurons studied produced responses to short tonal bursts, these responses having two components—initial discharges arising in response to the sound, and afterdischarge occurring after pauses of 50–100 msec. Afterdischarges lasted at least several seconds, and were generally characterized by a rhythmic structure (with a frequency of 8–12 Hz). After electrical microstimulation, the level of spike activity increased, especially in afterdischarges, and this increase could last up to 4 h. Combined peristimulus histograms, cross-correlations, and gravitational analyses were used to demonstrate interactions of neurons, which increased after electrical stimulation and were especially pronounced in the response afterdischarges. Department of Neurosciences, Faculty of Medicine, University of Pennsylvania, Philadelphia, USA. Laboratory of Auditory Physiology, I. P. Pavlov Institute of Physiology, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 5-6, pp. 3–17, May–June, 1996.     

Estimating nerve excitation thresholds to cutaneous electrical stimulation by finite element modeling combined with a stochastic branching nerve fiber model

Electrical stimulation of cutaneous tissue through surface electrodes is an often used method for evoking experimental pain. However, at painful intensities both non-nociceptive Aβ-fibers and nociceptive Aδ- and C-fibers may be activated by the electrical stimulation. This study proposes a finite element (FE) model of the extracellular potential and stochastic branching fiber model of the afferent fiber excitation thresholds. The FE model described four horizontal layers; stratum corneum, epidermis, dermis, and hypodermal used to estimate the excitation threshold of Aβ-fibers terminating in dermis and Aδ-fibers terminating in epidermis. The perception thresholds of 11 electrodes with diameters ranging from 0.2 to 20 mm were modeled and assessed on the volar forearm of healthy human volunteers by an adaptive two-alternative forced choice algorithm. The model showed that the magnitude of the current density was highest for smaller electrodes and decreased through the skin. The excitation thresholds of the Aδ-fibers were lower than the excitation thresholds of Aβ-fibers when current was applied through small, but not large electrodes. The experimentally assessed perception threshold followed the lowest excitation threshold of the modeled fibers. The model confirms that preferential excitation of Aδ-fibers may be achieved by small electrode stimulation due to higher current density in the dermoepidermal junction.     

A microcontroller system for investigating the catch effect: functional electrical stimulation of the common peroneal nerve

Correction of drop foot in hemiplegic gait is achieved by electrical stimulation of the common peroneal nerve with a series of pulses at a fixed frequency. However, during normal gait, the electromyographic signals from the tibialis anterior muscle indicate that muscle force is not constant but varies during the swing phase. The application of double pulses for the correction of drop foot may enhance the gait by generating greater torque at the ankle and thereby increase the efficiency of the stimulation with reduced fatigue. A flexible controller has been designed around the Odstock Drop Foot Stimulator to deliver different profiles of pulses implementing doublets and optimum series. A peripheral interface controller (PIC) microcontroller with some external circuits has been designed and tested to accommodate six profiles. Preliminary results of the measurements from a normal subject seated in a multi-moment chair (an isometric torque measurement device) indicate that profiles containing doublets and optimum spaced pulses look favourable for clinical use.     

The principle of electrical carotid sinus nerve stimulation: A nerve pacemaker system for angina pectoris and hypertension therapy

Electrical carotid sinus nerve stimulation (CSNS) via an implanted electrode receiver assembly, radio frequency coupled to an external signal generator, is an experimental therapy for hypertension and angina pectoris. CSNS increases afferent information to the central nervous system exerting neurally regulated decreases in heart rate, stroke volume, and blood pressure. No nonspecific side effects are observed, in contrast to drug therapy. A nerve pacemaker system is described and compared to the commonly used open-loop stimulator system (fixed frequency and intensity CSNS). It is a closed-loop system, controlled by heart rate (as an indicator of the state of “arousal” and of sympathetic activity) and, thereby, feedback-controlled by its therapeutic effects. The miniaturized (hybrid technology) system consists of an ECG amplifier, a stimulus pattern memory with I-O periphery and a transmitter, including an antenna coil to be coupled to the implanted assembly. Stimulus parameters (frequency and amplitude of impulses) are optimized for each patient individually. Stimulus patterns (pulse synchronous amplitude modulated groups of impulses) are adapted to the patient's cardiovascular situation. The nerve pacemaker may be an alternative to drug therapy or major surgery in both diseases. Compatible with the open-loop system, it replaces the first step in previously treated CSNS patients. Clinical application was possible through cooperation with the Department of Cardiology, Medical Clinic, Bonn University, Bonn, Germany, FRG (Prof. Schaede, Prof. Simon and Dr. Schilling). The miniaturized (hybrid technology) version of the nerve pacemaker was realized through cooperation with the Berlin Technical University (W. George). Parts of this work were sponsored by Stiftung Volkswagenwerk and Deutsche Forschungsgemeinschaft.     

Response to electrical stimulation of the median nerve in the human newborn

Four normal full-term newborns and 4 adults were stimulated by constant-current square-wave pulses to the median nerve at the wrist. Thumb and finger movement thresholds were determined by visual observation and by recording movement potentials from the thenar eminence. Afferent nerve action potential thresholds were determined by recording from the median nerve above the elbow. Subjective sensory thresholds were also determined by verbal report in the adults. Somesthetic evoked responses (SEP) were recorded from the contralateral scalp at movement threshold and 2 times the movement threshold in both infants and adults. The mean afferent nerve action potential threshold of the newborns was 3 times higher than that of the adults. The mean movement thresholds of newborns and adults were not significantly different. The mean action potential threshold was not different from the mean subjective sensory threshold in the adults. The mean action potential threshold was not different from the mean movement threshold in the newborns. Shocks of movement threshold intensity are not always adequate for elicitation of afferent action potentials and SEP's in newborns. In stimulating peripheral nerves to elicit SEP's, the positions of the stimulating electrodes are critical.     

Excitatory/inhibitory response types in the cochlear nucleus: relationships to discharge patterns and responses to electrical stimulation of the auditory nerve

We have studied the response properties of single units in the cochlear nucleus of unanesthetized decerebrate cats. The purpose of the study was to compare the properties of cochlear nucleus units as described in two commonly used classification schemes. Units were first classified according to their receptive-field properties based on the relative prominence of excitatory and inhibitory responses to tones and noise. Units were then classified on the basis of their discharge patterns to short tone bursts at their best frequencies (BFs). Our results show that systematic relationships exist between the receptive-field properties and discharge patterns of cochlear nucleus units. Type I units give only excitatory responses to tones and noise. They are characterized by primary-like and chopper discharge patterns. Some units in the anteroventral cochlear nucleus have prepotentials in their spike waveforms. Prepotential units most often show primary-like discharge patterns, but prepotential units characterized by nonprimary-like discharge patterns are also found. Most prepotential units lack detectable inhibitory sidebands (type I), but two of the nonprimary-like prepotential units encountered in this study had inhibitory sidebands (type III). Type III units also give excitatory responses to BF tones, but they have inhibitory sidebands. Most type III units give chopper discharge patterns, and these units can be recorded throughout the cochlear nucleus. Some type III units in the dorsal cochlear nucleus give complex discharge patterns that can be described as a composite of the pauser pattern and other patterns. The complexity of these responses seems to increase as the amount of inhibition at BF increases. Type I/III units give excitatory responses to tones and noise, but have little or no spontaneous activity so they cannot be tested directly for inhibitory responses. Type I/III units typically show chopper discharge patterns. One group of type I/III units have rate-level functions with sloping saturation, suggesting that these may receive a predominance of input from low spontaneous rate auditory nerve fibers. Type II units are nonspontaneous and give excitatory responses to tones, but give weak or no responses to noise. While type II units are homogeneous as a group in terms of their response maps. BF rate-level functions, and responses to noise, they show a variety of discharge patterns in response to short tone bursts at BF.(ABSTRACT TRUNCATED AT 400 WORDS)     

Facial muscle reanimation by transcutaneous electrical stimulation for peripheral facial nerve palsy

Abstract

Reanimation of paralysed facial muscles by electrical stimulation has been studied extensively in animal models, but human studies in this field are largely lacking. Twenty-four subjects with a peripheral facial nerve palsy with a median duration of three years were enrolled. We studied activations of four facial muscles with electrical stimulation using surface electrodes. In subjects whose voluntary movement was severely impaired or completely absent, the electrical stimulation produced a movement that was greater in amplitude compared with the voluntary effort in 10 out of 18 subjects in the frontalis muscle, in 5 out of 14 subjects in the zygomaticus major muscle, and in 3 out of 8 subjects in the orbicularis oris muscle. The electrical stimulation produced a stronger blink in 8 subjects out of 22 compared with their spontaneous blinks. The stimulation could produce a better movement even in cases where the muscles were clinically completely paretic, sometimes also in palsies that were several years old, provided that the muscle was not totally denervated. Restoring the function of paralysed facial muscles by electrical stimulation has potential as a therapeutic option in cases where the muscle is clinically paretic but has reinnervation.     

A simple swivel for intracranial electrical stimulation

A simple swivel for intracranial stimulation (ICS) in freely moving animals is described. The assembly consists of a commercially available terminal tap, mercotac swivel and receptacle. The swivel is inexpensive, requires no machining and can not be disconnected by the animal.     

Use of transcutaneous electrical nerve stimulation in the complex treatment of glossalgia

Thirty-four patients with glossalgia were studied. The painful part of tongue was electrically stimulated using an ‘élektronika-2M’ apparatus with a current of 45 μA for 10–20 min (current strength was patient-controlled to produce the sensation of local prickling); courses consisted of 10–12 treatments. The results of electrical stimulation therapy were compared with results obtained using standard methods of treatment (novocaine blockade, analgesics, etc.), which were used in a control group of 30 patients. Transcutaneous electrical nerve stimulation was highly effective: improvements were noted after the first session, and significant reductions in pain syndrome occurred after 1–3 sessions; therapeutic effects were obtained at the end of treatment in all 34 patients, i.e., in 100% of cases, as compared with 70% in the control group, with remission lasting more than one year in 20 patients and from 3–12 months in 14. Department of Nerve Diseases, Faculty of Stomatology, N. A. Semashko Moscow Medical Stomatological Institute; Department of Therapeutic Stomatology, N. N. Burdenko Voronezh State Medical Institute. Translated from Zhurnal Nevrologii i Psikhiarii imeni S. S. Korsakova, Vol. 95, No. 5, pp. 19–21, September–October, 1995.