Normal-hearing Human Subjects Research Articles

Tone-evoked acoustic change complex (ACC) in an animal model

The auditory change complex (ACC) is a cortical evoked potential complex generated in response to a change (e.g., frequency or level) within an ongoing auditory stimulus. The ACC has been recorded in both normal-hearing human subjects and in cochlear implant users, suggesting that the ACC would be useful in clinical applications. Here, we investigate the feasibility of recording ACC in response to frequency or level changes in sedated cats. Five purpose-bred cats were sedated with ketamine and acepromazine. Continuous tones alternated between high and low frequencies or levels in 500-ms blocks. Frequency and level steps were varied parametrically. Scalp potentials were recorded with needle electrodes (two active electrodes = one on each hemisphere, reference: mastoid, ground = back of the cat). ACC was successfully elicited in all cats by both frequency and level steps. In many cases, ACCs were markedly greater for increasing or for decreasing stimulus steps. The discrimination thresholds measured were in good agreement with previous behavioral studies in which cats where trained to perform similar frequency or level discriminations. The results indicate that the ACC will be a useful tool for evaluating novel acoustical or electrical stimulation modes that are not yet feasible in humans.

Time-domain analysis of distortion-product otoacoustic emissions using a hydrodynamic cochlea model

Abstract As a by-product of nonlinear amplification in the cochlea, the inner ear emits sound waves in response to two tones with different frequencies. These sound waves are measurable in the ear canal as distortion-product otoacoustic emissions (DPOAEs). DPOAEs putatively consist of two components emerging at different locations in the cochlea. Wave interference between the two components limits the accuracy of DPOAEs as a noninvasive measure of cochlear function. Using short stimulus pulses instead of continuous stimuli, the two DPOAE components can be separated in the time domain due to their different latencies. The present work utilizes a nonlinear hydrodynamic cochlea model to simulate short-pulse DPOAEs in the time domain. When adding irregularities to the mechanical parameters of the model, the simulated DPOAE signals show two distinguishable components and long-lasting beat tones, similar to band-pass filtered experimental data from normal-hearing human subjects. The model results suggest that the beat tones can occur solely due to interference of the coherent-reflection component with the fading nonlinear-distortion component.

Cochlear tuning and phase-locking assessed with complementary techniques within the same species, and extrapolation to humans

The cochlea decomposes sound into bands of its constituent frequencies and encodes the temporal waveform of these bands. These two properties generate frequency-tuning and phase-locking in individual neurons of the auditory nerve. The relative roles of frequency tuning and phase-locking toward important aspects of perception, e.g., the coding of speech and pitch, are heavily debated. Characterization of the limits of these processes in humans may help to clarify these relative roles. We studied threshold and suprathreshold frequency tuning, as well as phase-locking to the fine-structure of sound, by recording from single-fibers in the auditory nerve of different species, including chinchilla, cat, and macaque monkey. We also developed stimulus and analysis paradigms to study frequency tuning and phase-locking via mass potentials recorded near the cochlear round window, and applied these techniques to these same species as well as to normal hearing human subjects. The comparison of bandwidths of single fibers with mass potentials within the same species allows us to infer bandwidths of single fibers from human mass potential data. Combined with behavioral and otoacoustic emission data, the evidence suggests that the human auditory nerve is unusual in its sharpness of frequency tuning but not in its range of phase-locking.

Distortion-Product Otoacoustic Emission Measured Below 300Hz in Normal-Hearing Human Subjects.

Physiological noise levels in the human ear canal often exceed naturally low levels of otoacoustic emissions (OAEs) near the threshold of hearing. Low-frequency noise, and electronic filtering to cope with it, has effectively limited the study of OAE to frequencies above about 500Hz. Presently, a custom-built low-frequency acoustic probe was put to use in 21 normal-hearing human subjects (of 34 recruited). Distortion-product otoacoustic emission (DPOAE) was measured in the enclosed ear canal volume as the response to two simultaneously presented tones with frequencies f 1 and f 2. The stimulus-frequency ratio f 2/f 1 was varied systematically to find the "optimal" ratio evoking the largest level at 2 f 1-f 2 frequencies 87.9, 176, and 264Hz. No reference data exist in this frequency region. Results show that DPOAE exists down to at least 87.9Hz, maintaining the bell-shaped dependence on the f 2/f 1 ratio known from higher frequencies. Toward low frequencies, however, the bell broadens and the optimal ratio increases proportionally to the bandwidth of an auditory filter as defined by the equivalent rectangular bandwidth. The DPOAE phase rotates monotonously as a function of the stimulus ratio, and its slope trend supports the notion of a lack of scaling symmetry in the apex of the cochlea.

Auditory gap-in-noise detection behavior in ferrets and humans.

The precise encoding of temporal features of auditory stimuli by the mammalian auditory system is critical to the perception of biologically important sounds, including vocalizations, speech, and music. In this study, auditory gap-detection behavior was evaluated in adult pigmented ferrets (Mustelid putorius furo) using bandpassed stimuli designed to widely sample the ferret’s behavioral and physiological audiogram. Animals were tested under positive operant conditioning, with psychometric functions constructed in response to gap-in-noise lengths ranging from 3 to 270 ms. Using a modified version of this gap-detection task, with the same stimulus frequency parameters, we also tested a cohort of normal-hearing human subjects. Gap-detection thresholds were computed from psychometric curves transformed according to signal detection theory, revealing that for both ferrets and humans, detection sensitivity was worse for silent gaps embedded within low-frequency noise compared with high-frequency or broadband stimuli. Additional psychometric function analysis of ferret behavior indicated effects of stimulus spectral content on aspects of behavioral performance related to decision-making processes, with animals displaying improved sensitivity for broadband gap-in-noise detection. Reaction times derived from unconditioned head-orienting data and the time from stimulus onset to reward spout activation varied with the stimulus frequency content and gap length, as well as the approach-to-target choice and reward location. The present study represents a comprehensive evaluation of gap-detection behavior in ferrets, while similarities in performance with our human subjects confirm the use of the ferret as an appropriate model of temporal processing.

Auditory function in normal-hearing, noise-exposed human ears.

To determine whether suprathreshold measures of auditory function, such as distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs), are correlated with noise exposure history in normal-hearing human ears. Recent data from animal studies have revealed significant deafferentation of auditory nerve fibers after full recovery from temporary noise-induced hearing loss. Furthermore, these data report smaller ABR wave I amplitudes in noise-exposed animal ears when compared with non-noise-exposed control animals or prenoise exposure amplitudes in the same animal. It is unknown whether a similar phenomenon exists in the normal-hearing, noise-exposed human ear. Thirty normal-hearing human subjects with a range of noise exposure backgrounds (NEBs) participated in this study. NEB was quantified by the use of a noise exposure questionnaire that extensively queried loud sound exposure during the previous 12 months. DPOAEs were collected at three f2s (1, 2, and 4 kHz) over a range of L2s. DPOAE stimulus level began at 80 dB forward-pressure level and decreased in 10 dB steps. Two-channel ABRs were collected in response to click stimuli and 4 kHz tone bursts; one channel used an ipsilateral mastoid electrode and the other an ipsilateral tympanic membrane electrode. ABR stimulus level began at 90 dB nHL and was decreased in 10 dB steps. Amplitudes of waves I and V of the ABR were analyzed. A statistically significant relationship between ABR wave I amplitude and NEB was found for clicked-evoked ABRs recorded at a stimulus level of 90 dB nHL using a mastoid recording electrode. For this condition, ABR wave I amplitudes decreased as a function of NEB. Similar systematic trends were present for ABRs collected in response to clicks and 4 kHz tone bursts at additional suprathreshold stimulation levels (≥70 dB nHL). The relationship weakened and disappeared with decreases in stimulation level (≤60 dB nHL). Similar patterns were present for ABRs collected using a tympanic membrane electrode. However, these relationships were not statistically significant and were weaker and more variable than those collected using a mastoid electrode. In contrast to the findings for ABR wave I, wave V amplitude was not significantly related to NEB. Furthermore, there was no evidence of a systematic relationship between suprathreshold DPOAEs and NEB. A systematic trend of smaller ABR wave I amplitudes was found in normal-hearing human ears with greater amounts of voluntary NEB in response to suprathreshold clicks and 4 kHz tone bursts. These findings are consistent with the data from previous work completed in animals, where the reduction in suprathreshold responses was a result of deafferentation of high-threshold/low-spontaneous rate auditory nerve fibers. These data suggest that a similar mechanism might be operating in human ears after exposure to high sound levels. However, evidence of this damage is only apparent when examining suprathreshold wave I amplitude of the ABR. In contrast, suprathreshold DPOAE level was not significantly related to NEB. This was expected, given noise-induced auditory damage findings in animal ears did not extend to the outer hair cells, the generator for the DPOAE response.

Characteristics of the 2f1-f2 distortion product otoacoustic emission in a normal hearing population

Distortion-product otoacoustic emission (DPOAE) fine structure and component characteristics are reported between 0.75 and 16 kHz in 356 clinically normal hearing human subjects ages 10 to 65 yr. Stimulus tones at 55/40, 65/55, and 75/75 dB SPL were delivered using custom designed drivers and a calibration method that compensated for the depth of insertion of the otoacoustic emission (OAE) probe in the ear canal. DPOAE fine structure depth and spacing were found to be consistent with previous reports with depth varying between 3 and 7 dB and average spacing ratios (f/Δf) between 15 and 25 depending on stimulus level and frequency. In general, fine structure depth increased with increasing frequency, likely due to a diminishing difference between DPOAE component levels. Fine structure spacing became wider with increasing age above 8 kHz. DPOAE components were extracted using the inverse fast Fourier transform method, adhering to a strict signal to noise ratio criterion for clearer interpretation. Component data from four age groups between 18 and 55 yr old were available for the stimulus levels of 75/75 dB SPL. The age groups could be differentiated with greater than 90% accuracy when using the level of the component presumed to originate from the DPOAE characteristic frequency place. This accuracy held even for frequencies at and below 4 kHz where the age groups exhibited similar average hearing thresholds.

Multiple indices of the 'bounce' phenomenon obtained from the same human ears.

Loud low-frequency sounds can induce temporary oscillatory changes in cochlear sensitivity, which have been termed the 'bounce' phenomenon. The origin of these sensitivity changes has been attributed to slow fluctuations in cochlear homeostasis, causing changes in the operating points of the outer hair cell mechano-electrical and electro-mechanical transducers. Here, we acquired three objective and subjective measures resulting in a comprehensive dataset of the bounce phenomenon in each of 22 normal-hearing human subjects. We analysed the level and phase of cubic and quadratic distortion product otoacoustic emissions and the auditory thresholds before and after presentation of a low-frequency stimulus (30 Hz sine wave, 120 dB SPL, 90 s) as a function of time. In addition, the perceived loudness of temporary, tinnitus-like sensations occurring in all subjects after cessation of the low-frequency stimulus was tracked over time. The majority of the subjects (70 %) showed a significant, biphasic change of quadratic, but not cubic, distortion product otoacoustic emissions of about 3-4 dB. Eighty-six percent of the tested subjects showed significant alterations of hearing thresholds after low-frequency stimulation. Four different types of threshold changes were observed, namely monophasic desensitisations (the majority of cases), monophasic sensitisations, biphasic alterations with initial sensitisation and biphasic alterations with initial desensitisation. The similar duration of the three bounce phenomenon measures indicates a common origin. The current findings are consistent with the hypothesis that slow oscillations of homeostatic control mechanisms and associated operating point shifts within the cochlea are the source of the bounce phenomenon.

Latency of tone-burst-evoked auditory brain stem responses and otoacoustic emissions: Level, frequency, and rise-time effects

Simultaneous measurement of auditory brain stem response (ABR) and otoacoustic emission (OAE) delays may provide insights into effects of level, frequency, and stimulus rise-time on cochlear delay. Tone-burst-evoked ABRs and OAEs (TBOAEs) were measured simultaneously in normal-hearing human subjects. Stimuli included a wide range of frequencies (0.5-8 kHz), levels (20-90 dB SPL), and tone-burst rise times. ABR latencies have orderly dependence on these three parameters, similar to previously reported data by Gorga et al. [J. Speech Hear. Res. 31, 87-97 (1988)]. Level dependence of ABR and TBOAE latencies was similar across a wide range of stimulus conditions. At mid-frequencies, frequency dependence of ABR and TBOAE latencies were similar. The dependence of ABR latency on both rise time and level was significant; however, the interaction was not significant, suggesting independent effects. Comparison between ABR and TBOAE latencies reveals that the ratio of TBOAE latency to ABR forward latency (the level-dependent component of ABR total latency) is close to one below 1.5 kHz, but greater than two above 1.5 kHz. Despite the fact that the current experiment was designed to test compatibility with models of reverse-wave propagation, existing models do not completely explain the current data.

Distortion product otoacoustic emissions upon ear canal pressurization

The purpose of this study was to quantify the change in distortion product otoacoustic emission (DPOAE) level upon ear canal pressurization. DPOAEs were measured on 12 normal-hearing human subjects for ear canal static pressures between -200 and +200 daPa in (50 ± 5) daPa steps. A clear dependence of DPOAE levels on the pressure was observed, with levels being highest at the maximum compliance of the middle ear, and decreasing on average by 2.3 dB per 50 daPa for lower and higher pressures. Ear canal pressurization can serve as a tool for improving the detectability of DPOAEs in the case of middle-ear dysfunction.

Digital Music Exposure Reliably Induces Temporary Threshold Shift in Normal-Hearing Human Subjects

One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Is it necessary to penalize impulsive noise +5 dB due to higher risk of hearing damage?

It is studied whether the +5 dB penalty for impulsiveness established by ISO 1999:1990 accounts for a higher risk of noise-induced hearing loss. A total of 16 normal-hearing human subjects were exposed for 10 min to two types of binaural industrial-recordings: (1) a continuous broad-band noise normalized to L(EX,8 h)=80 dBA and (2) the combination of the previous stimulus with an impulsive noise normalized to L(EX,8 h)=75+5(db penalty)=80 dBA (peak level 117 dBC and repetition rate of 0.5 impacts per second). Distortion product otoacoustic emissions (DPOAEs) were measured in a broad frequency range before and in the following 90 min after the exposure. The group results show that the continuous exposure had a bigger impact on DPOAE levels, with a maximum DPOAE shift of approximately 5 dB in the frequency range of 2-3.15 kHz during the first 10 min of the recovery. No evident DPOAE shift is seen for the impulsive + continuous stimulus. The results indicate that the penalty overestimated the effects on DPOAE levels and support the concept that the risk of hearing loss from low-level impulses may be predicted on an equal-energy basis.

Recovery of distortion-product otoacoustic emissions after a 2-kHz monaural sound-exposure in humans: Effects on fine structures

A better understanding of the vulnerability of the fine structures of distortion-product otoacoustic emissions (DPOAEs) after acoustic overexposure may improve the knowledge about DPOAE generation, cochlear damage, and lead to more efficient diagnostic tools. It is studied whether the DPOAE fine structures of 16 normal-hearing human subjects are systematically affected after a moderate monaural sound-exposure of 10 min to a 2-kHz tone normalized to an exposure level L(EX,8h) of 80 dBA. DPOAEs were measured before and in the following 70 min after the exposure. The experimental protocol allowed measurements with high time and frequency resolution in a 1/3-octave band centered at 3 kHz. On average, DPOAE levels were reduced approximately 5 dB in the entire measured frequency-range. Statistically significant differences in pre- and post-exposure DPOAE levels were observed up to 70 min after the end of the sound exposure. The results show that the effects on fine structures are highly individual and no systematic change was observed.

A normative study of tympanic membrane motion in humans using a laser Doppler vibrometer (LDV)

Laser Doppler vibrometry was used to measure the sound-induced tympanic membrane (TM) velocity, assessed near the umbo, in 56 normal hearing human subjects at nine sound frequencies. A second series of measurements was made in 47 subjects with sensorineural hearing loss (SNHL). Each set of measurements has features in common with previously published results. The measured velocity magnitude (normalized by the stimulus sound pressure) at any one frequency ranged among subjects by factors of 3–0.3 (±10 dB) from the mean and the phase angle of the normalized velocity ranged from ±15° around the mean at low frequencies to more than ±200° around the mean at 6 kHz. Measurements repeated after intervals of minutes to months were generally within 40% in magnitude (±3 dB) and 20° in phase. Sources of variability included the effect of small differences in the location of the measurement on the TM and small static middle-ear pressures. No effects of stimulus level, ear sidedness (right or left), gender, age or the presence or absence of SNHL were found. These results provide a baseline normal response for studies of TM velocity with conductive hearing losses of different etiologies.

Contralateral suppression of transiently evoked otoacoustic emissions by harmonic complex tones in humans.

Variations in the amplitude of transiently evoked otoacoustic emissions (TEOAEs) produced by a contralateral complex tone were measured in 26 normal-hearing human subjects. TEOAEs were evoked using a 1-kHz tone pip at 60 dB SPL. The contralateral complex consisted of harmonic components with frequencies between 400 and 2000 Hz; it was presented at levels ranging from 40 to 50 dB SL and its fundamental frequency (F0) was varied. In experiment 1, the dependence of TEOAE amplitude variations on the F0 of the contralateral complex was measured by varying the F0 from 50 to 400 Hz in octave steps. The results revealed a nonmonotonic dependence of TEOAE amplitude variations on contralateral F0, with significantly larger TEOAE suppression for F0's of 100 and 200 Hz than for F0's of 50 and 400 Hz. Experiment 2, in which the harmonics were summed in alternating sine-cosine phase instead of constant sine phase, showed a shift of the function relating TEOAE attenuation to F0 towards lower F0's, indicating that the waveform repetition rate, rather than harmonic spacing, was the actual factor of the dependence of contralateral TEOAE attenuation on F0. Furthermore, significantly smaller suppression was observed with the alternating-phase complexes than with the sine-phase complexes, suggesting an influence of the waveform crest factor. Experiment 3 showed no difference between the contralateral TEOAE attenuation effects produced by positive and negative Schroeder-phase complexes. Overall, these results bring further arguments for the notion that contralaterally induced medial olivocochlear bundle (MOCB) activity, as measured through the contralateral suppression of TEOAEs in humans, is sensitive to the rate of temporal envelope fluctuations of the contralateral stimulus, with preferential rates around 100-200 Hz.

Contralateral acoustic stimulation induces a phase advance in evoked otoacoustic emissions in humans

In 28 normal-hearing human subjects, the medial olivocochlear efferent system was activated by contralateral acoustic stimulation which is able to mimic the inhibitory effects of electrical stimulation of the crossed olivocochlear bundle. A first experiment on 16 subjects demonstrated that a contralateral white noise of 35 dB SL was able to induce temporal changes on transiently evoked otoacoustic emissions in response to clicks of 63 dB SPL. These temporal changes consisted of an advance of click-evoked otoacoustic signals in 87% of cases and is referred to as phase-shift effect. The phase advance, quantified using two signal processing methods in both time and frequency domains, was found to be mainly associated with lower frequencies, with a maximal effect at 1.5 kHz and minimal effects around 3.5 and 4 kHz. In a second experiment, carried out on 12 subjects, a negative relationship was found to exist between the ipsilateral stimulation level (level of clicks ranging from 57 to 69 dB SPL) and the phase-shift effect (PSE). Specifically in the range of levels tested (25–45 dB SL), a linear relationship presenting no obvious saturation effect was observed between the contralateral level and the PSE. The PSE was examined in 6 additional subjects exhibiting pathological symptoms; 2 of 3 individuals, who had no contralateral stapedial reflexes unilaterally, showed the PSE whereas this response was reduced or absent in 3 other subjects in the ear with severed efferents associated with a vestibular neurotomy. The integrity of olivocochlear efferents was, therefore, necessary to obtain a full effect, but the absence of stapedial reflex did not prevent the effect from occurring.

On the nature of nonmonotonic notches in input/output functions of 2f1–f2 acoustic distortion products

To better understand the nature of nonmonotonic notches in input/output (I/O) functions of 2f1–f2 acoustic distortion products (ADP), I/O functions were examined in 10 young, normal-hearing human subjects in conjunction with measurements of the ADP fine frequency structure [Gaskill and Brown, J. Acoust. Soc. Am. 88, 821–839 (1990)]. Primary frequencies were incremented in 1/32-oct. steps, the f2/f1 ratio was 1.2, and the primary levels were equal. ADP fine structure was measured over a 1/6 to 1/3 octave surrounding either 2000 or 4000 Hz with primary levels between 45 to 65 dB SPL in 2.5-dB steps. As primary level increased, a downward frequency shift of the peaks and valleys of the ADP fine structure was observed. This shift is responsible for the nonmonotonic notch and the wide variety of shapes of the I/O functions. As a result, even small changes in the frequency or level ratio of the primaries can drastically alter the shape of the I/O function. [Work supported by NIH-NIDCD P50-DC00422.]

Human auditory temporal summation in the presence of ipsilateral or contralateral continuous tones

The auditory temporal summation function was measured in 16 normal hearing human subjects using a set of five single‐burst and seven multiple‐burst tones of 2.0 kHz. In each of two experiments, thresholds were obtained: in the presence of a 60 dB SPL continuous tone one‐third octave above or below the stimulus frequency of 2.0 kHz, and in the quiet condition. In experiment I, the continuous tone was presented ipsilaterally and in experiment II, the tone was presented contralateral to the stimulus. It was shown that the ipsilateral tone conditions significantly reduced the slope of the temporal summation functions, whereas the contralateral continuous tone conditions had no influence. Second, it was concluded that a common mechanism processed both single‐ and multiple‐burst stimuli. Finally, it was concluded that a power function was a simple and adequate way of describing the temporal summation process.

Coherence analysis of scalp responses to amplitude-modulated tones

Magnitude squared coherence is a method of auditory evoked potential (AEP) frequency-domain analysis, measuring the degree to which the AEP is determined by the stimulus as a function of frequency. In 10 normal-hearing human subjects, scalp responses to an amplitude-modulated (AM) tone (500 Hz carrier modulated with a 40 Hz envelope) were recorded. Critical value criteria were utilized in the statistical analysis of coherence-intensity functions for determination of threshold responses. When compared with subjective determination of AEP threshold from time-domain waveforms, coherence analysis provided a significantly (p less than 0.001) more sensitive threshold measure. Coherence analysis provides information on the spectral content of the response, and allows for the objective determination of threshold which may potentially be utilized in a more expeditious threshold measurement scheme.

Cross-correlation of the frequency-following response

Frequency-following responses (FFRs) to a low-frequency stimulus in 16 normal-hearing human subjects were cross-correlated with the stimulus in an attempt to yield more easily recognizable FFRs at lower intensity levels and increase threshold sensitivity. Cross-correlation of these responses with the stimulus did not improve threshold sensitivity and latencies obtained from the cross-correlated FFRs showed more variability and were uniformly shorter than those of standard FFR measurement.