Low energy magnetic stimulation of the phrenic nerve - a simulation study.

Peripheral magnetic stimulation is a promising assistive technique for rehabilitation. Today's magnetic stimulation devices, designed for transcranial stimulation, operate at currents of 6 kA and higher. This makes them expensive and bulky. Many motor neurons in peripheral nerves are more accessible, have large diameters, and require significantly lower field strengths for stimulation. In this work, we present a simulation environment to determine the threshold current required to trigger an action potential in phrenic nerve motor neurons for different coil geometries. An anatomical model was used for coil placement and realistic field calculations. The field distribution was calculated using the finite integration technique and then applied to a neuronal model to simulate the axon membrane dynamics. For general applicability, the coil-nerve distance and the axon diameter were varied. We show that the required current was approximately 1.3 kA for a nerve-coil distance of 35 mm, which corresponds to 20% of the available power of a commercial TMS device. By including the nearby vagus nerve in the simulations, we showed that accidental stimulation of this nerve is highly unlikely. Our results pave the way for the development of smaller, less complex, and more affordable stimulators and promise to increase the use of peripheral magnetic stimulators in clinical settings.

Optimal pulse configuration for peripheral inductive nerve stimulation.

Peripheral magnetic stimulation is a promising technique for several applications like rehabilitation or diagnose of neuronal pathways. However, most available magnetic stimulation devices are designed for transcranial stimulation and require high-power, expensive hardware. Modern technology such as rectangular pulses allows to adapt parameters like pulse shape and duration in order to reduce the required energy. Nevertheless, the effect of different temporal electromagnetic field shapes on neuronal structures is not yet fully understood. We created a simulation environment to find out how peripheral nerves are affected by induced magnetic fields and what pulse shapes have the lowest energy requirements. Using the electric field distribution of afigure-of-8coil together with an axon model in saline solution, we calculated the potential along the axon and determined the required threshold current to elicit an action potential. Further, for the purpose of selective stimulation, we investigated different axon diameters. Our results show that rectangular pulses have the lowest thresholds at a pulse duration of 20µs. For sinusoidal coil currents, the optimal pulse duration was found to be 40µs. Most importantly, with an asymmetric rectangular pulse, the coil current could be reduced from 2.3 kA (cosine shaped pulse) to 600 A. In summary, our results indicate that for magnetic nerve stimulation the use of rectangular pulse shapes holds the potential to reduce the required coil current by a factor of 4, which would be a massive improvement.

[VOTE versus ACLTE: comparison of two snoring noise classifications using machine learning methods]. / VOTE versus ACLTE: Vergleich zweier Schnarchgeräuschklassifikationen mit Methoden des maschinellen Lernens.

BACKGROUND: Acoustic snoring sound analysis is a noninvasive method for diagnosis of the mechanical mechanisms causing snoring that can be performed during natural sleep. The objective of this work is development and evaluation of classification schemes for snoring sounds that can provide meaningful diagnostic support. MATERIALS AND METHODS: Based on two annotated snoring noise databases with different classifications (s-VOTE with four classes versus ACLTE with five classes), identically structured machine classification systems were trained. The feature extractor openSMILE was used in combination with a linear support vector machine for classification. RESULTS: With an unweighted average recall (UAR) of 55.4% for the s­VOTE model and 49.1% for the ACLTE, the results are at a similar level. In both models, the best differentiation is achieved for epiglottic snoring, while velar and oropharyngeal snoring are more often confused. CONCLUSION: Automated acoustic methods can help diagnose sleep-disordered breathing. A reason for the restricted recognition performance is the limited size of the training datasets.

[Conversion of sound into auditory nerve action potentials]. / Codierung von Schallsignalen in Aktionspotenziale des auditorischen Nervs.

Outer hair cells play a major role in the hearing process: they amplify the motion of the basilar membrane up to a 1000-fold and at the same time sharpen the excitation patterns. These patterns are converted by inner hair cells into action potentials of the auditory nerve. Outer hair cells are delicate structures and easily damaged, e. g., by overexposure to noise. Hearing aids can amplify the amplitude of the excitation patterns, but they cannot restore their degraded frequency selectivity. Noise overexposure also leads to delayed degeneration of auditory nerve fibers, particularly those with low a spontaneous rate, which are important for the coding of sound in noise. However, this loss cannot be diagnosed by pure-tone audiometry.

Temporal interaction in electrical hearing elucidates auditory nerve dynamics in humans.

In cochlear implants, severe limitations arise from electrical crosstalk between channels. Therefore, the current trend in cochlear implants is to increase stimulation rates to encode signals with higher temporal precision. However, the fundamental question: "What is the limit of temporal precision due to inherent neuronal dynamics of the stimulated neurons?" has not yet been resolved. In this study we have developed a double-pulse method and, for the first time, reversed stimulus polarity systematically between consecutive pulses to elucidate subthreshold-induced temporal interaction effects. This method allowed us to determine the time-course of subthreshold temporal interaction in human subjects which identifies the limits of encoded temporal precision. Our results show significant temporal interaction up to 600 µs inter-pulse interval. In all the cases tested we saw a facilitation effect on threshold. Interaction effects at a 20% below threshold pre-conditioning stimulation showed up to 38% ± 6% threshold reduction. These results imply that there is significant temporal interaction between two subsequent pulses. This interaction diminishes the precision of amplitude coding. We predict interaction effects on temporal precision and channel interaction. For (interleaved) stimulation with short inter-pulse intervals it is interesting to consider our interaction results; and it may become important to consider them for future coding strategies where high temporal precision is required. In an increasing group of binaural implanted patients this will be the case when interaural time differences are encoded with µs precision.

Subpixel tracking for the analysis of outer hair cell movements.

CONCLUSION: Videomicroscopy with subpixel analysis is an excellent system for quantification of outer hair cell (OHC) movements. The resolution of a few nanometers is accurate enough to show induced differences of electromotility. OBJECTIVE: Electromotility of OHCs is a voltage-dependent process resulting from a membrane protein named prestin. Voltage sensitivity is conferred to prestin by intracellular anions. Reduction of these anions reduces electromotility. Videomicroscopy and subpixel tracking combine video-based analysis with a resolution of few nanometers. The aim of this study was to show the feasibility of a system for quantification of OHC movements. MATERIALS AND METHODS: Electromotility was investigated under normal and reduced intracellular chloride conditions. Cells were stimulated by the patch-clamp technique. Voltage steps were 500 ms long, ranging from -170 to +30 mV in 10 mV steps. RESULTS: As in previous studies our results show the following. The direction of OHC movement depends on the polarity of voltage steps, length changes are not equal for symmetrical voltage steps of opposite polarity, average shortening for a depolarizing step (-70 mV to +30 mV) is about 13 nm/mV. Hyperpolarization (-70 mV to -170 mV) on average evokes elongations of about 3 nm/mV. Half maximal chloride concentration reduces motility by 14%; half maximal electromotility is reached by a 94% reduction of chloride.

Three-dimensional motion of the organ of Corti.

The vibration of the organ of Corti, a three-dimensional micromechanical structure that incorporates the sensory cells of the hearing organ, was measured in three mutually orthogonal directions. This was achieved by coupling the light of a laser Doppler vibrometer into the side arm of an epifluorescence microscope to measure velocity along the optical axis of the microscope, called the transversal direction. Displacements were measured in the plane orthogonal to the transverse direction with a differential photodiode mounted on the microscope in the focal plane. Vibration responses were measured in the fourth turn of a temporal-bone preparation of the guinea-pig cochlea. Responses were corrected for a "fast" wave component caused by the presence of the hole in the cochlear wall, made to view the structures. The frequency responses of the basilar membrane and the reticular lamina were similar, with little phase differences between the vibration components. Their motion was rectilinear and vertical to the surface of their membranes. The organ of Corti rotated about a point near the edge of the inner limbus. A second vibration mode was detected in the motion of the tectorial membrane. This vibration mode was directed parallel to the reticular lamina and became apparent for frequencies above approximately 0.5 oct below the characteristic frequency. This radial vibration mode presumably controls the shearing action of the hair bundles of the outer hair cells.

Characteristics of the travelling wave in the low-frequency region of a temporal-bone preparation of the guinea-pig cochlea.

This study provides a detailed quantitative description of the acoustically evoked vibration responses in the low-frequency region of the in vitro guinea-pig cochlea. Responses of the basilar membrane, the reticular lamina and Hensen cells were measured with a laser Doppler vibrometer, without the need for introducing artificial light reflectors. The apex of the cochlea was opened, leaving the helicotrema intact. Two response components were detected: a 'fast' component, which was probably caused by the hole in the cochlea, and a 'slow' component, which shared the features of a classical travelling wave. The velocity response of the 'slow' component exhibited a relatively flat low-frequency slope (15 dB/oct) and a much steeper high-frequency roll-off (third turn: -47 dB/oct; fourth turn: -35 dB/oct). The group delay was dependent on the characteristic frequency. In the fourth turn, the sharpness of the velocity tuning curves (Q(10 dB): 1.0) was similar to those of in vivo mechanical and neural recordings, whereas in the third turn the tuning (Q(10 dB): 1.1) was much less than for in vivo recordings. The results indicate that cochlear amplification, which is responsible for the high sensitivity and sharp tuning in the basal part of the cochlea, is much less pronounced in the apical turn of the cochlea.

Limiting dynamics of high-frequency electromechanical transduction of outer hair cells.

High-frequency resolution is one of the salient features of peripheral sound processing in the mammalian cochlea. The sensitivity originates in the active amplification of the travelling wave on the basilar membrane by the outer hair cells (OHCs), where electrically induced mechanical action of the OHC on a cycle-by-cycle basis is believed to be the crucial component. However, it is still unclear if this electromechanical action is sufficiently fast and can produce enough force to enhance mechanical tuning up to the highest frequencies perceived by mammals. Here we show that isolated OHCs in the microchamber configuration are able to overcome fluid forces with almost constant displacement amplitude and phase up to frequencies well above their place-frequency on the basilar membrane. The high-frequency limit of the electromotility, defined as the frequency at which the amplitude drops by 3 dB from its asymptotic low-frequency value, is inversely dependent on cell length. The frequency limit is at least 79 kHz. For frequencies up to 100 kHz, the electromotile response was specified by an overdamped (Q = 0.42) second-order resonant system. This finding suggests that the limiting factor for frequencies up to 100 kHz is not the speed of the motor but damping and inertia. The isometric force produced by the OHC was constant at least up to 50 kHz, with amplitudes as high as 53 pN/mV being observed. We conclude that the electromechanical transduction process of OHCs possesses the necessary high-frequency properties to enable amplification of the travelling wave over the entire hearing range.

Dynamics of middle ear prostheses - simulations and measurements.

The efficient and systematic development of a middle ear prosthesis necessitates the use of computer models for the prosthesis itself and the reconstructed middle ear. The structure and parameters of the computer model have to be verified by specific measurements of the implant and the reconstructed ear. To obtain a realistic model of a reconstructed ear, three steps of modeling and measurements have been carried out. To get a first approach of the coupling elements a mechanical test rig representing a simplified reconstructed middle ear was built. The velocity of the stapedial footplate was measured with a laser Doppler vibrometer. The corresponding computer model was formulated, and the respective parameters were determined using the measured dynamical transfer functions. In the second step, a prosthesis was implanted into a human temporal bone without inner ear. Exciting this system with noise, the velocity of the stapes footplate was measured with the laser Doppler vibrometer. Based on the multibody system approach, a mechanical computer model was generated to describe the spatial motions of the reconstructed ossicular chain. Varying some significant parameters, simulations have been carried out. To describe the dynamical behavior of the system consisting of middle and inner ear, the computer model used in the second step has been enlarged by adding a simplified structure of the inner ear. The results were compared with in situ measurements taken from living humans.

Monitoring noise susceptibility: sensitivity of otoacoustic emissions and subjective audiometry.

The capacity of different audiological methods to detect a high noise susceptibility was examined in 20 normally hearing and 26 especially noise-susceptible subjects. The latter were selected from 422 soldiers in field studies: they had shown a temporary threshold shift (TTS) in pure tone audiometry (PTA) after regular training with firearms. In laboratory experiments, the TTS-positive soldiers were re-examined using greatly reduced sound intensities, which caused no TTS in a control subject group. Before and after acoustic stimulation, different subjective (PTA, high frequency audiometry (HFA), upper limit of hearing (ULH)) and objective (transiently evoked otoacoustic emissions (TEOAE), distortion products (DPOAE)) audiological tests were performed. After exposure to low impact noise in the laboratory, in both PTA and HFA, a TTS was observed in 11.5% (N = 3) of the noise-susceptible group (compared to 0% in the control group). In the TTS-positive group, deterioration of the ULH occurred in 28% (N = 7) (compared to 15% (N = 3) in the control group). An ULH improvement occurred in only one subject (3.8%) (compared to 25% (N = 5) in the control group). Significant alterations of click-evoked OAE-amplitudes were found in 26.9% (N = 7) of the selected groups, whereas stable emissions were observed in all but one subject (5%) of the control group. However, DPOAE alterations were seen in 19.2% (N = 5) of the TTS-positive soldiers but also in 25% (N = 5) of the control group. These results suggest that TEOAE provides a more sensitive and more objective method of detecting a subtle noise-induced disturbance of cochlear function than do PTA or DPOAE.

[Laser vibrometry. A middle ear and cochlear analyzer for noninvasive studies of middle and inner ear function disorders]. / Laservibrometrie. Ein Mittelohr- und Kochleaanalysator zur nicht-invasiven Untersuchung von Mittel- und Innenohrfunktionsstörungen.

A complete battery of audiometric methods is required for the differential diagnosis of different hearing disabilities (including puretone audiometry, impedance, stapes reflex, speech audiometry, brainstam evoked response audiometry, otoacoustic emissions, etc.). In many cases, a comprehensive diagnosis is not possible. Here we describe a new technique based on a laser-Doppler vibrometer that has the potential for non-invasive diagnosis not only middle ear disease but also cochlear pathologies. Disturbance of cochlear function can be ascertained because the input impedance of the cochlea acts as a mechanical load on the middle ear and therefore influences motion of the umbo. In the present study vibration of the umbo and eardrum were measured with a commercially available laser-Doppler vibrometer coupled directly into a standard surgical microscope. The use of the microscope allowed non-invasive measurements of vibrations without having to introduce reflecting material onto the tympanic membrane. Sound pressure was measured with a calibrated probe microphone placed near the tympanic membrane. The displacement response and the specific acoustic impedance of the umbo were calculated from the velocity and sound pressure measured. For normal hearing subjects, the amplitude of the umbo's displacement for frequencies from 0.1 kHz to 1 kHz was 1 nm at 60 dB SPL and decreased with a slope of 6 dB/octave for frequencies between 1 and 5 kHz. A strong correlation was found between the specific acoustic impedance of the umbo and hearing thresholds for hearing-impaired subjects (having otosclerosis or sensorineural hearing losses). The frequency response of the umbo proved to be a means for evaluating the function of both the middle ear and the cochlea under pathological conditions. The measurement technique described is also suitable for intraoperative investigation of the frequency response of the opened middle ear, as well as for the in situ frequency response of partial and total ossicular replacement prostheses.

Resonant tectorial membrane motion in the inner ear: its crucial role in frequency tuning.

The tectorial membrane has long been postulated as playing a role in the exquisite sensitivity of the cochlea. In particular, it has been proposed that the tectorial membrane provides a second resonant system, in addition to that of the basilar membrane, which contributes to the amplification of the motion of the cochlear partition. Until now, technical difficulties had prevented vibration measurements of the tectorial membrane and, therefore, precluded direct evidence of a mechanical resonance. In the study reported here, the vibration of the tectorial membrane was measured in two orthogonal directions by using a novel method of combining laser interferometry with a photodiode technique. It is shown experimentally that the motion of the tectorial membrane is resonant at a frequency of 0.5 octave (oct) below the resonant frequency of the basilar membrane and polarized parallel to the reticular lamina. It is concluded that the resonant motion of the tectorial membrane is due to a parallel resonance between the mass of the tectorial membrane and the compliance of the stereocilia of the outer hair cells. Moreover, in combination with the contractile force of outer hair cells, it is proposed that inertial motion of the tectorial membrane provides the necessary conditions to allow positive feedback of mechanical energy into the cochlear partition, thereby amplifying and tuning the cochlear response.

Abolition of the receptor potential response of isolated mammalian outer hair cells by hair-bundle treatment with elastase: a test of the tip-link hypothesis.

To test the hypothesis that the tip-links of hair-cell stereocilia are essential for mechanoelectrical transduction, tip-links of isolated outer hair cells (OHCs) of the guinea-pig cochlea were eliminated with a proteolytic enzyme, elastase, and the influence on the receptor potential measured with the whole-cell patch-clamp technique. Within 45 s of immersion of the hair bundle in 20 IU/ml elastase, the receptor potential in response to direct deflection of the hair bundle was irreversibly abolished. The electrical input impedance of the cell remained unchanged, implying that the channels of the basolateral membrane were not affected by elastase. The effect of elastase on the receptor potential was comparable to changes seen after mechanically induced hair-bundle damage. As a further control, a putative transduction-channel blocker, dihydrostreptomycin (68 microM), which does not affect tip-links, was applied to the hair bundle. Although the receptor potential was also blocked by dihydrostreptomycin, the effect was reversible. The results suggest that tip-links are required for mechanoelectrical transduction of mammalian OHCs.

Sound-induced displacement responses in the plane of the organ of Corti in the isolated guinea-pig cochlea.

Sound-induced displacement responses in the plane of the organ of Corti were studied in the apical turn in the isolated temporal-bone preparation of the guinea-pig cochlea. Swept sinusoidal sound stimuli (100-500 Hz) were delivered closed-field to the external auditory meatus. The surface of the organ of Corti was continuously monitored using a CCD video camera. Displacement responses in the plane of the organ of Corti were determined by analyzing the change of the location of the cells (pixel-by-pixel) within the visual field of the microscope. Displacement responses followed the stimulus amplitude and were observable at Hensen's cells, three rows of outer hair cells and inner hair cells. The most prominent displacement responses were over the outer hair cells; the maximum amplitude was 0.6-1.7 microns at 100 dB SPL. Tuned displacement responses were found; the Q10 dB was 1.3 +/- 0.6. The best frequency was tonotopically organized, decreasing toward the apex with a space constant of 0.4-0.9 mm/oct. The motion was directed either strial-apically or strial-basally in a frequency dependent manner. With the aid of laser interferometric measurements of the transverse displacement, it was concluded that sound stimulation does not induce slow DC motion in the organ of Corti for the isolated temporal-bone preparation.

[Comparison of methods for early detection of noise vulnerability of the inner ear. Amplitude reduction of otoacoustic emissions are most sensitive at submaximal noise impulse exposure]. / Methodenvergleich zur Früherkennung einer Lärm-vulnerabilität des Innenohres. Amplitudenreduktion otoakustischer Emissionen am empfindlichsten bei subriskanter Impulsschallreizung.

Noise-induced temporary impairment of cochlear function was measured with several audiometric tests in order to evaluate which method best predicts a vulnerable cochlea. We tested 10 normally-hearing and 13 subjects who were positive for temporary threshold shifts (TTS). The latter were selected from 194 soldiers who demonstrated a TTS higher than 15 dB after regular training with firearms. Acoustic distortion products (DPOAE), click-evoked otoacoustic emissions (TEOAE), upper limit of hearing (ULH) and pure-tone and high-frequency audiometry were used to evaluate possible increased vulnerability of the cochlea. Tests were conducted at lower sound intensities (white noise, 90 dB SPL, 5 min; impact noise, 100 or 106 dB SPLs, 10 impulses/s, 5 min). Seventy per cent of the TTS-positive soldiers studied exhibited significant reductions of TEOAE amplitudes, whereas a stable emission was observed in all control subjects. DPOAE alterations were seen in 38% of the soldiers tested. These results indicate that TEOAE is the most sensitive, objective method for detecting a positive disturbance in cochlear function. Although the upper limit of hearing was also a very sensitive method, variability of this psychoacoustic method depended on the help and experience of the subjects being tested.

Electromotility of outer hair cells from the cochlea of the echolocating bat, Carollia perspicillata.

Isolated outer hair cells (OHCs) and explants ot the organ of Corti were obtained from the cochlea of the echolocating bat, Carollia perspicillata, whose hearing range extends up to about 100 kHz. The OHCs were about 10-30 microns long and produced resting potentials between -30 to -69 mV. During stimulation with a sinusoidal extracellular voltage field (voltage gradient of 2 mV/microns) cyclic length changes were observed in isolated OHCs. The displacements were most prominent at the level of the cell nucleus and the cuticular plate. In the organ of Corti explants, the extracellular electric field induced a radial movement of the cuticular plate which was observed using video subtraction and photodiode techniques. Maximum displacements of about 0.3-0.8 microns were elicited by stimulus frequencies below 100 Hz. The displacement amplitude decreased towards the noise level of about 10-30 nm for stimulus frequencies between 100-500 Hz, both in apical and basal explants. This compares well with data from the guinea pig, where OHC motility induced by extracellular electrical stimulation exhibits a low pass characteristic with a corner frequency below 1 kHz. The data indicate that fast OHC movements presumably are quite small at ultrasonic frequencies and it remains to be solved how they participate in amplifying and sharpening cochlear responses in vivo.

Profound reversible CD4+ T lymphocytopenia in a severely uremic patient.

We report a human immunodeficiency virus antibody-negative, profoundly uremic patient who presented with a CD4+ T lymphocyte count of 133/mm3, a CD8+ T lymphocyte count of 77/mm3, and a CD3+ T lymphocyte count of 259/mm3. These values decrease significantly below reported levels in other lymphopenic uremic patients. High-efficiency chronic hemodialysis resulted in correction of these cytopenias to a normal range within 12 weeks.

Frequency response of mature guinea-pig outer hair cells to stereociliary displacement.

Outer hair cells (OHC) were isolated from the apical two turns of the guinea-pig cochlea and their hair-bundle stimulated mechanically by a glass probe. In accordance with in vivo data (Dallos, 1985), the resting membrane potential was typically -64 mV (N = 200). The maximum amplitudes of the receptor potentials were between 0.4 and 5.2 mV peak-to-peak, with mean of 1.5 mV +/- 0.9 mV (N = 81). The sensitivity was 0.015 mV/nm or 2 mV/deg. The frequency response of the receptor potential followed a first order low-pass filter characteristic with a corner frequency of about 63 Hz. For frequencies up to at least 1.6 kHz, the frequency response of mechanoelectrical transduction was dominated by the electrical input impedance of the cell. The presence of a single time constant in the voltage response to stereociliary deflection implies that the frequency response of mechanoelectrical transduction far exceeds that of the electrical input impedance of the cell; its time constant must be faster than 100 microseconds. Under in vivo conditions, OHC should be capable of providing a sufficiently large receptor potential to supply enough energy for electromechanical feedback.

[Mechanical stimulation of isolated outer hair cells as a test system. Inhibition of transduction by streptomycin treatment]. / Mechanische Reizung isolierter äusserer Haarzellen als Testsystem. Hemmung der Transduktion durch Streptomycinbehandlung.

Deflection of the hair bundle of isolated outer hair cells from the guinea pig cochlea can induce a receptor potential. Outer hair cells from the third and fourth turns of the guinea pig cochlea were isolated according to the method described by Zenner et al. Cells were maintained in Hank's balanced salt solution at room temperature. The whole cell potential was measured by the patch-clamp technique with soda glass capillaries (resistance 3-5 M omega) filled with KCl-Ringer solution. After compensation for the junction potential the stable resting potential of 46 cells was -63 mV +/- 5 mV. The hair bundle was deflected sinusoidally, with amplitudes ranging from 6 degrees to a maximum of 31 degrees in the positive direction (i.e., in the direction of the longest stereocilium). The stimulus was a piezo-driven glass capillary with an opening diameter of 5 microns. This mechanical stimulation induced in 33% of all stimulated cells (n = 46) a receptor potential response of 2.1 +/- 1.4 mV (maximally 5.5 mV). Deflection of the hair bundle in the opposite direction led to no change in the membrane potential, i.e. the cells were not hyperpolarized (minimal resolution 0.5 mV). Since the resting potential of the cells was more positive than the potassium equilibrium potential under our experimental conditions, the receptor current was most likely mediated by an influx of Na+ ions into the cell. The receptor potential response could be completely and reversibly blocked by the addition of dihydro-streptomycin.(ABSTRACT TRUNCATED AT 250 WORDS)