The dynamic range of inner hair cell and organ of Corti responses

Inner hair cell (IHC) and organ of Corti (OC) responses are measured from the apical three turns of the guinea pig cochlea, allowing access to regions with best, or most sensitive, frequencies at approximately 250, 1000, and 4000 Hz. In addition to measuring both ac and dc receptor potentials, the average value of the half-wave rectified response (AVEHR) is computed to better reflect the signal that induces transmitter release. This measure facilitates comparisons with single-unit responses in the auditory nerve. Although IHC ac responses exhibit compressive growth, response magnitudes at high levels depend on stimulus frequency. For example, IHCs with moderate and high best frequencies (BF) exhibit more linear responses below the BF of the cell, where higher sound-pressure levels are required to approach saturation. Because a similar frequency dependence is observed in extracellular OC responses, this phenomenon may originate in cochlear mechanics. At the most apical recording location, however, the pattern documented at the base of the cochlea is not seen in IHCs with low BFs around 250 Hz. In fact, more linear behavior is measured above the BF of the cell. These frequency-dependent features require modification of cochlear models that do not provide for longitudinal variations and generally depend on a single stage of saturation located at the synapse. Finally, behavior of dc and AVEHR responses suggests that a single IHC is capable of coding intensity over a large dynamic range [Patuzzi and Sellick, J. Acoust. Soc. Am. 74, 1734-1741 (1983); Smith et al., in Hearing--Physiological Bases and Psychophysics (Springer, Berlin, 1983); Smith, in Auditory Function (Wiley, New York, 1988)] and that information compiled over wide areas along the cochlear partition is not essential for loudness perception, consistent with psychophysical results [Viemeister, Hearing Res. 34, 267-274 (1988)].     

Finding the impedance of the organ of Corti

Measurements of the nonlinear response of the basilar membrane to a pure tone are shown to have a simple form for moderate membrane velocities: V(x,f;Vu)/Vu approximately [V(x,f)/Vu]v(x,f), f less than or equal to fc(x), where the response V is the velocity of the membrane at measurement position x, Vu is the umbo velocity, f is the frequency of the stimulus, and fc(x) is the local characteristic frequency. The frequency dependence of the functions v(x,f) and V(x,f) is determined from the data, and v(x,f) and ln V(x,f) are shown to be analytic functions in the lower half of the complex frequency plane, with Re [v(x,f)] a monotonically increasing function of f at fixed x. The linear limit of basilar membrane motion is characterized by a transfer function T(x,f) = (V/V1)v/(1-v), estimated by extrapolating V(x,f;Vu)/Vu to a small membrane velocity V1.T(x,f) and ln T(x,f) are shown to be analytic functions in the lower half of the complex frequency plane. The inverse of the amplitude of the transfer function, which has both a deep dip at f approximately fc(x) and a broad shoulder at lower frequencies, bears a striking resemblance to the neural threshold tuning curve. The functional form of T(x,f) is used to deduce the equation governing the motion of a section of the organ of Corti. Each section acts like a negatively damped harmonic oscillator stabilized at time t by a feedback force proportional to the velocity at the previous time t-tau. The time delay tau is proportional to the oscillator period [tau approximately 1.75/fc(x)]. Like a laser, the organ of Corti pumps energy into harmonic traveling waves. Unlike the laser, the direction of energy flow abruptly reverses as the traveling wave approaches the point of maximum membrane velocity [fc(x) approximately f]. All accumulated wave energy is then pumped back into a small section of the organ of Corti where transduction presumably occurs. Outer hair cells are conjectured to be active elements contributing to the negative damping and feedback of the cochlear amplifier.     

Sex differences in the length of the organ of Corti in humans

Sato et al. [Acta. Otolaryngol. 111 (6), 1037-1040 (1991)] reported that the human cochlea is, on average, 15% longer for males than females. This corresponds to 4.7 mm in length and to 2.78 standard deviations (SD). Anatomical measurements of the lengths of cochleas from 148 heads (194 cochleas) from eleven sources are reviewed and summarized. A sex difference of 3.36% is observed. This corresponds to 1.11 mm in length and to 0.49 SD. The mean lengths of the male and female cochleas are approximately 34 and 33 mm, respectively, and the population SD is 2.28 mm. The statistical significance of the observed difference is questionable.     

Properties of distortion product otoacoustic emissions and neural suppression tuning curves attributable to the tectorial membrane resonance

Mechanically coupled cochlear structures are likely to form a resonator with several degrees of freedom. Consequently one can expect complex, frequency-dependent relative movements between these structures, particularly between the tectorial membrane and reticular lamina. Shearing movement between these two structures excites the cochlear receptors. This excitation should be minimal at the frequency of the hypothesized tectorial membrane resonance. In each preparation, simultaneous masking neural tuning curves and distortion product otoacoustic emissions were recorded. The position of the low-frequency minima in the tuning curves, frequency dependence of the emission bandpass structure, and level-dependent phase reversal were compared to determine if they were generated by a common phenomenon, for example the tectorial membrane resonance. The notch in the masking curves and the phase inversion of the emission growth functions at the auditory thresholds are both situated half an octave below the probe frequency and the high-frequency primary, respectively, and show similar frequency dependence. The emission bandpass structure is, however, likely to be generated by a combination of mechanisms with different ones dominating at different stimulus parameters.     

Use of phase contrast microscopy to determine the height of the organ of Corti in whole-mount preparations

A technique has been developed to measure the height of the organ of Corti (OC) in the whole-mount preparations of the cochlear duct. The technique corrects for variations in the microscope system, such as the magnification of the objective lens and the mechanical properties of the fine-focus knob, as well as the refractive index of the embedding medium and the angle of specimens with respect to the optical axis of the microscope. At 11 percentage locations from apex to base, the height of the OC in ten chinchilla cochleas was measured at three positions: (1) the lateral edge of the inner hair cell (IHC); (2) the medial edge of the first row outer hair cell (OHC1); and (3) the lateral edge of the third row outer hair cell (OHC3). These measurements were compared to measurements made on radial sections from five other cochleas, with very good agreement at IHC and OHC3, and fairly good agreement at OHC1. The height at OHC3 varied almost linearly with percentage distance along the OC, ranging from 96 microns (apical end) to 51 microns (basal end). The height at the OHC1 varied from 77 to 49 microns, but did not vary linearly. The height of the IHC was relatively constant, from 50 to 60 microns, except at the basal end, where it decreased to 42 microns.     

The accuracy of hair cell counts in determining distance and position along the organ of Corti

The relationship between the density of hair cells (cells/mm) and measured distance along the guinea pig organ of Corti was determined using light microscopy and the surface specimen technique. It was demonstrated that the density of inner hair cells (IHC; mean 92.0 +/- 2.4) and 1st row of outer hair cells (OHC1; mean 118.7 +/- 2.3) did not show significant variation along the organ of Corti except within 0.5-1.0 mm of the apex and base where there was considerable variation between animals in the density of cells. There was a close relationship between the accumulated number of either IHC or OHC1 and distance from the base along the organ of Corti. Distances estimated by hair cell counts were similar to those determined by direct measurement. It is concluded that hair cell counts can be used to reliably estimate distances along the organ of Corti where accurate direct measurement is not possible, such as in scanning electron microscopy.     

BOLD responses to trigeminal nerve stimulation

The current study investigates a new model of barrel cortex activation using stimulation of the infraorbital branch of the trigeminal nerve. A robust and reproducible activation of the rat barrel cortex was obtained following trigeminal nerve stimulation. Blood oxygen level-dependent (BOLD) effects were obtained in the primary somatosensory barrel cortex (S1BF), the secondary somatosensory cortex (S2) and the motor cortex. These cortical areas were reached from afferent pathways from the trigeminal ganglion, the trigeminal nuclei and thalamic nuclei from which neurons project their axons upon whisker stimulation. The maximum BOLD responses were obtained for a stimulus frequency of 1 Hz, a stimulus pulse width of 100 μs and for current intensities between 1.5 and 3 mA. The BOLD response was nonlinear as a function of frequency and current intensity. Additionally, modeling BOLD responses in the rat barrel cortex from separate cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂) measurements showed good agreement with the shape and amplitude of measured BOLD responses as a function of stimulus frequency and will potentially allow to identify the sources of BOLD nonlinearities. Activation of the rat barrel cortex using trigeminal nerve stimulation will contribute to the interpretation of the BOLD signals from functional magnetic resonance imaging studies.     

Transient and sustained BOLD responses to sustained visual stimulation

Examining the transients of the blood-oxygenation-level-dependent (BOLD) signal using functional magnetic resonance imaging is a tool to probe basic brain physiology. In addition to the so-called initial dip and poststimulus undershoot of the BOLD signal, occasionally, overshoot at the beginning and at the end of stimulation and stimulus onset and offset ('phasic') responses are observed. Hemifield visual stimulation was used in human subjects to study the latter transients. As expected, sustained ('tonic') stimulus-correlated contralateral activation in the visual cortex and LGN was observed. Interestingly, bilateral phasic responses were observed, which only partly overlapped with the tonic network and which would have been missed using a standard analysis. A biomechanical model of the BOLD signal ('balloon model') indicated that, in addition to phasic neuronal activity, vascular uncoupling can also give rise to phasic BOLD signals. Thus, additional physiological information (i.e., cerebral blood flow) and examination of spatial distribution of the activity might help to assess the BOLD signal transients correctly. In the current study, although vascular uncoupled responses cannot be ruled out as an explanation of the observed phasic BOLD network, the spatial distribution argues that sustained hemifield visual stimulation evokes both bilateral phasic and contralateral sustained neuronal responses. As a consequence, in rapid event-related experimental designs, both the phasic and tonic networks cannot be separated, possibly confounding the interpretation of BOLD signal data. Furthermore, a combination of phasic and tonic responses in the same region of interest might also mimic a BOLD response typically observed in adaptation experiments.     

Vibration of curved plate assemblies subjected to membrane stresses

In a previous paper [1] the finite strip method was applied to the prediction of the natural frequencies of vibration of longitudinally invariant, rigidly connected assemblies of circularly curved and flat strips having diaphragm end supports. This work is extended here to include the presence of an initial membrane stress field. An individual curved strip may be subjected to a biaxial direct stress field comprising a uniform stress acting in the circumferential direction and a non-uniform stress acting in the longitudinal direction. The presence of the membrane stress field is accommodated in the analysis by the inclusion of an initial stress or geometric stiffness matrix. A further extension included here is a facility to delete in-surface inertia terms. Results are presented for the application of the strip method in predicting the frequencies of vibration of a circular cylinder subjected to a complicated membrane stress system.     

Vibration of a parallelogram membrane

The approximate natural frequencies of oblique membranes have been determined for arbitrary skew angles and side ratios. The response of such a membrane to a forcing function is then obtained in a similar fashion. The lower natural frequencies have been presented for various side ratios of the membrane as a function of the skew angle and vice versa. With increasing skew angle they increase rapidly. For large skew angles the lower natural frequencies are mainly made up by those of the index n = 1. This is especially valid for membranes of large side ratio.     

Inner hair cell responses to tonal stimulation in the presence of broadband noise

The effects of broadband noise (BBN) on the tone-evoked de receptor potential from inner hair cells of guinea pigs were measured. The effects of the noise were: suppression of the receptor potential, no net change, or greater depolarization relative to the tone alone, evoked receptor potential. The effects appear to be consistent with a two-tone suppression hypothesis. The time course of the suppression effect is immediate and constant in time. This observation suggests no obvious involvement of a local feedback loop in outer hair cells or one depending on the efferent nerves. Inner hair cell "sensitivity" is a variable in the magnitude of the suppression. Comparison of masked, tone-evoked de receptor potential intensity functions to responses from auditory-nerve fibers (taken from the literature for experiments using a similar paradigm) differentiates the phenomena of suppression and adaptation in the auditory periphery.     

Event-related fMRI with painful electrical stimulation of the trigeminal nerve

Several functional brain imaging studies of pain using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that painful stimulation causes activation of different brain areas. The aim of the present study was to develop and implement painful stimulation of the trigeminal nerve, which can be applied with event-related paradigms by using MRI. Twelve healthy, right-handed volunteers were examined. Painful electrical stimulation of the first trigeminal branch was performed. In an event-related setting with a 1.5 T clinical scanner with EPI capability, the following fMRI parameters were used: 20 slices, 3 mm thickness, isotropic voxel, 306 measurements with 54 randomized events. Statistical postprocessing was performed with SPM99. Activation of the ipsi- and contralateral secondary somatosensory cortex (SII), and the contralateral insular cortex was observed as well as a contralateral thalamic activation (T=4.45, extension 15 voxels). Six of the 12 volunteers revealed also activation of the cingulate cortex. The investigation demonstrates that painful stimulation of the trigeminal nerve activates the contralateral insular cortex, SII, and thalamus, as well as the ipsilateral SII. In contrast to other studies, the cingulate cortex was only activated inconsistently.     

Auditory nerve fiber responses to electric stimulation: modulated and unmodulated pulse trains

Many modern cochlear implants use sound processing strategies that stimulate the cochlea with modulated pulse trains. Rubinstein et al. [Hear. Res. 127, 108 (1999)] suggested that representation of the modulator in auditory nerve responses might be improved by the addition of a sustained, high-rate, desynchronizing pulse train (DPT). In addition, activity in response to the DPT may mimic the spontaneous activity (SA) in a healthy ear. The goals of this study were to compare responses of auditory nerve fibers in acutely deafened, anesthetized cats elicited by high-rate electric pulse trains delivered through an intracochlear electrode with SA, and to measure responses of these fibers to amplitude-modulated pulse trains superimposed upon a DPT. Responses to pulse trains showed variability from presentation to presentation, but differed from SA in the shape of the envelope of the interval histogram (IH) for pulse rates above 4.8 kpps (kilo pulses per second). These IHs had a prominent mode near 5 ms that was followed by a long tail. Responses to modulated biphasic pulse trains resembled responses to tones in intact ears for small (<10%) modulation depths, suggesting that acousticlike responses to sinusoidal stimuli might be obtained with a DPT. However, realistic responses were only observed over a narrow range of levels and modulation depths. Improved coding of complex stimulus waveforms may be achieved by signal processing strategies for cochlear implants that properly incorporate a DPT.     

Hemodynamic responses in human multisensory and auditory association cortex to purely visual stimulation

Background  

Recent findings of a tight coupling between visual and auditory association cortices during multisensory perception in monkeys and humans raise the question whether consistent paired presentation of simple visual and auditory stimuli prompts conditioned responses in unimodal auditory regions or multimodal association cortex once visual stimuli are presented in isolation in a post-conditioning run. To address this issue fifteen healthy participants partook in a "silent" sparse temporal event-related fMRI study. In the first (visual control) habituation phase they were presented with briefly red flashing visual stimuli. In the second (auditory control) habituation phase they heard brief telephone ringing. In the third (conditioning) phase we coincidently presented the visual stimulus (CS) paired with the auditory stimulus (UCS). In the fourth phase participants either viewed flashes paired with the auditory stimulus (maintenance, CS-) or viewed the visual stimulus in isolation (extinction, CS+) according to a 5:10 partial reinforcement schedule. The participants had no other task than attending to the stimuli and indicating the end of each trial by pressing a button.     

Vulnerability to re-entry in simulated two-dimensional cardiac tissue: effects of electrical restitution and stimulation sequence

Ventricular fibrillation is a lethal arrhythmia characterized by multiple wavelets usually starting from a single or figure-of-eight re-entrant circuit. Understanding the factors regulating vulnerability to the re-entry is essential for developing effective therapeutic strategies to prevent ventricular fibrillation. In this study, we investigated how pre-existing tissue heterogeneities and electrical restitution properties affect the initiation of re-entry by premature extrastimuli in two-dimensional cardiac tissue models. We studied two pacing protocols for inducing re-entry following the "sinus" rhythm (S1) beat: (1) a single premature (S2) extrastimulus in heterogeneous tissue; (2) two premature extrastimuli (S2 and S3) in homogeneous tissue. In the first case, the vulnerable window of re-entry is determined by the spatial dimension and extent of the heterogeneity, and is also affected by electrical restitution properties and the location of the premature stimulus. The vulnerable window first increases as the action potential duration (APD) difference between the inside and outside of the heterogeneous region increases, but then decreases as this difference increases further. Steeper APD restitution reduces the vulnerable window of re-entry. In the second case, electrical restitution plays an essential role. When APD restitution is flat, no re-entry can be induced. When APD restitution is steep, re-entry can be induced by an S3 over a range of S1S2 intervals, which is also affected by conduction velocity restitution. When APD restitution is even steeper, the vulnerable window is reduced due to collision of the spiral tips.