A frequency peak at 3.1 kHz obtained from the spectral analysis of the cochlear implant electrocochleography noise.

INTRODUCTION: The functional evaluation of auditory-nerve activity in spontaneous conditions has remained elusive in humans. In animals, the frequency analysis of the round-window electrical noise recorded by means of electrocochleography yields a frequency peak at around 900 to 1000 Hz, which has been proposed to reflect auditory-nerve spontaneous activity. Here, we studied the spectral components of the electrical noise obtained from cochlear implant electrocochleography in humans. METHODS: We recruited adult cochlear implant recipients from the Clinical Hospital of the Universidad de Chile, between the years 2021 and 2022. We used the AIM System from Advanced Bionics® to obtain single trial electrocochleography signals from the most apical electrode in cochlear implant users. We performed a protocol to study spontaneous activity and auditory responses to 0.5 and 2 kHz tones. RESULTS: Twenty subjects including 12 females, with a mean age of 57.9 ± 12.6 years (range between 36 and 78 years) were recruited. The electrical noise of the single trial cochlear implant electrocochleography signal yielded a reliable peak at 3.1 kHz in 55% of the cases (11 out of 20 subjects), while an oscillatory pattern that masked the spectrum was observed in seven cases. In the other two cases, the single-trial noise was not classifiable. Auditory stimulation at 0.5 kHz and 2.0 kHz did not change the amplitude of the 3.1 kHz frequency peak. CONCLUSION: We found two main types of noise patterns in the frequency analysis of the single-trial noise from cochlear implant electrocochleography, including a peak at 3.1 kHz that might reflect auditory-nerve spontaneous activity, while the oscillatory pattern probably corresponds to an artifact.

A Brainstem reticulotegmental neural ensemble drives acoustic startle reflexes.

The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhibition of the RtTg glutamatergic neurons decreases the ASR amplitudes. Viral tracing reveals an ASR neural circuit that the cochlear nucleus carrying auditory information sends direct excitatory innervations to the RtTg glutamatergic neurons, which in turn project to spinal motor neurons. Together, our findings describe a functional role of RtTg and its related neural circuit in startle reflexes, and demonstrate how the RF connects auditory system with motor functions.

Envelope following responses predict speech-in-noise performance in normal-hearing listeners.

Permanent threshold elevation after noise exposure or aging is caused by loss of sensory cells; however, animal studies show that hair cell loss is often preceded by degeneration of the synapses between sensory cells and auditory nerve fibers. Silencing these neurons is likely to degrade auditory processing and may contribute to difficulties understanding speech in noisy backgrounds. Reduction of suprathreshold ABR amplitudes can be used to quantify synaptopathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy preferentially targets fibers with high thresholds and low spontaneous rate and because phase locking to temporal envelopes is particularly strong in these fibers, measuring envelope following responses (EFRs) might be a more robust measure of cochlear synaptopathy. A recent auditory model further suggests that modulation of carrier tones with rectangular envelopes should be less sensitive to cochlear amplifier dysfunction and, therefore, a better metric of cochlear neural damage than sinusoidal amplitude modulation. In this study, we measure performance scores on a variety of difficult word-recognition tasks among listeners with normal audiograms and assess correlations with EFR magnitudes to rectangular versus sinusoidal modulation. Higher harmonics of EFR magnitudes evoked by a rectangular-envelope stimulus were significantly correlated with word scores, whereas those evoked by sinusoidally modulated tones did not. These results support previous reports that individual differences in synaptopathy may be a source of speech recognition variability despite the presence of normal thresholds at standard audiometric frequencies.NEW & NOTEWORTHY Recent studies suggest that millions of people may be at risk of permanent impairment from cochlear synaptopathy, the age-related and noise-induced degeneration of neural connections in the inner ear. This study examines electrophysiological responses to stimuli designed to improve detection of neural damage in subjects with normal hearing sensitivity. The resultant correlations with word recognition performance are consistent with a contribution of cochlear neural damage to deficits in hearing in noise abilities.

Spectrally specific temporal analyses of spike-train responses to complex sounds: A unifying framework.

Significant scientific and translational questions remain in auditory neuroscience surrounding the neural correlates of perception. Relating perceptual and neural data collected from humans can be useful; however, human-based neural data are typically limited to evoked far-field responses, which lack anatomical and physiological specificity. Laboratory-controlled preclinical animal models offer the advantage of comparing single-unit and evoked responses from the same animals. This ability provides opportunities to develop invaluable insight into proper interpretations of evoked responses, which benefits both basic-science studies of neural mechanisms and translational applications, e.g., diagnostic development. However, these comparisons have been limited by a disconnect between the types of spectrotemporal analyses used with single-unit spike trains and evoked responses, which results because these response types are fundamentally different (point-process versus continuous-valued signals) even though the responses themselves are related. Here, we describe a unifying framework to study temporal coding of complex sounds that allows spike-train and evoked-response data to be analyzed and compared using the same advanced signal-processing techniques. The framework uses a set of peristimulus-time histograms computed from single-unit spike trains in response to polarity-alternating stimuli to allow advanced spectral analyses of both slow (envelope) and rapid (temporal fine structure) response components. Demonstrated benefits include: (1) novel spectrally specific temporal-coding measures that are less confounded by distortions due to hair-cell transduction, synaptic rectification, and neural stochasticity compared to previous metrics, e.g., the correlogram peak-height, (2) spectrally specific analyses of spike-train modulation coding (magnitude and phase), which can be directly compared to modern perceptually based models of speech intelligibility (e.g., that depend on modulation filter banks), and (3) superior spectral resolution in analyzing the neural representation of nonstationary sounds, such as speech and music. This unifying framework significantly expands the potential of preclinical animal models to advance our understanding of the physiological correlates of perceptual deficits in real-world listening following sensorineural hearing loss.

Reduced suprathreshold auditory nerve responses are associated with slower processing speed and thinner temporal and parietal cortex in presbycusis.

Epidemiological evidence shows an association between hearing loss and dementia in elderly people. However, the mechanisms that connect hearing impairments and cognitive decline are still unknown. Here we propose that a suprathreshold auditory-nerve impairment is associated with cognitive decline and brain atrophy. METHODS: audiological, neuropsychological, and brain structural 3-Tesla MRI data were obtained from elders with different levels of hearing loss recruited in the ANDES cohort. The amplitude of waves I (auditory nerve) and V (midbrain) from auditory brainstem responses were measured at 80 dB nHL. We also calculated the ratio between wave V and I as a proxy of suprathreshold brainstem function. RESULTS: we included a total of 101 subjects (age: 73.5 ± 5.2 years (mean ± SD), mean education: 9.5 ± 4.2 years, and mean audiogram thresholds (0.5-4 kHz): 25.5 ± 12.0 dB HL). We obtained reliable suprathreshold waves V in all subjects (n = 101), while replicable waves I were obtained in 92 subjects (91.1%). Partial Spearman correlations (corrected by age, gender, education and hearing thresholds) showed that reduced suprathreshold wave I responses were associated with thinner temporal and parietal cortices, and with slower processing speed as evidenced by the Trail-Making Test-A and digit symbol performance. Non-significant correlations were obtained between wave I amplitudes and other cognitive domains. CONCLUSIONS: These results evidence that reduced suprathreshold auditory nerve responses in presbycusis are associated with slower processing speed and brain structural changes in temporal and parietal regions.

Contralateral suppression of otoacoustic emissions in pre-school children.

BACKGROUND: Contralateral suppression of otoacoustic emissions (OAEs) may serve as an index of the medial olivocochlear (MOC) reflex. To date, this index has been studied in various populations but never in pre-school children. The purpose of this study was to fill this gap and describe how the MOC reflex affects the properties of transiently evoked OAEs (TEOAEs) in this age group. In addition, the influence of the presence of spontaneous OAEs (SOAEs) in the studied ear on the suppression of TEOAEs was also investigated. METHODS: TEOAEs with and without contralateral acoustic stimulation (CAS) by white noise were measured in 126 normally hearing pre-school children aged 3-6 years. The values of response levels, suppression by CAS, and signal-to-noise ratios (SNRs) of TEOAEs were investigated for the whole signal (global) and for half-octave frequency bands from 1 to 4 kHz. Only ears with SNR >6 dB were used in the analyses. SOAEs were acquired using the so-called synchronized SOAEs (SSOAEs) technique. RESULTS: Ears with SSOAEs had higher response levels and SNRs than ears without SSOAEs, and suppression was lower (0.58 dB compared to 0.85 dB). Only 22% of all studied ears had an SNR >20 dB, a level recommended in some studies for measuring suppression. There were no significant effects of age or gender on TEOAE suppression. CONCLUSIONS: Suppression levels for pre-school children did not differ appreciably from those of adults measured under similar conditions in other studies. Taken together with no effect of age in the data studied here, it seems that there is no effect of age on TEOAE suppression. However, we did find that the presence of SSOAEs had an effect on TEOAE suppression, a finding which has not been reported in earlier studies on different populations. We suggest that the presence of SSOAEs might be a crucial factor related to MOC function.

Suppression tuning of spontaneous otoacoustic emissions in the barn owl (Tyto alba).

Spontaneous otoacoustic emissions (SOAEs) have been observed in a variety of different vertebrates, including humans and barn owls (Tyto alba). The underlying mechanisms producing the SOAEs and the meaning of their characteristics regarding the frequency selectivity of an individual and species are, however, still under debate. In the present study, we measured SOAE spectra in lightly anesthetized barn owls and suppressed their amplitudes by presenting pure tones at different frequencies and sound levels. Suppression effects were quantified by deriving suppression tuning curves (STCs) with a criterion of 2 dB suppression. SOAEs were found in 100% of ears (n = 14), with an average of 12.7 SOAEs per ear. Across the whole SOAE frequency range of 3.4-10.2 kHz, the distances between neighboring SOAEs were relatively uniform, with a median distance of 430 Hz. The majority (87.6%) of SOAEs were recorded at frequencies that fall within the barn owl's auditory fovea (5-10 kHz). The STCs were V-shaped and sharply tuned, similar to STCs from humans and other species. Between 5 and 10 kHz, the median Q10dB value of STC was 4.87 and was thus lower than that of owl single-unit neural data. There was no evidence for secondary STC side lobes, as seen in humans. The best thresholds of the STCs varied from 7.0 to 57.5 dB SPL and correlated with SOAE level, such that smaller SOAEs tended to require a higher sound level to be suppressed. While similar, the frequency-threshold curves of auditory-nerve fibers and STCs of SOAEs differ in some respects in their tuning characteristics indicating that SOAE suppression tuning in the barn owl may not directly reflect neural tuning in primary auditory nerve fibers.

Neuronal population model of globular bushy cells covering unit-to-unit variability.

Computations of acoustic information along the central auditory pathways start in the cochlear nucleus. Bushy cells in the anteroventral cochlear nucleus, which innervate monaural and binaural stations in the superior olivary complex, process and transfer temporal cues relevant for sound localization. These cells are categorized into two groups: spherical and globular bushy cells (SBCs/GBCs). Spontaneous rates of GBCs innervated by multiple auditory nerve (AN) fibers are generally lower than those of SBCs that receive a small number of large AN synapses. In response to low-frequency tonal stimulation, both types of bushy cells show improved phase-locking and entrainment compared to AN fibers. When driven by high-frequency tones, GBCs show primary-like-with-notch or onset-L peristimulus time histograms and relatively irregular spiking. However, previous in vivo physiological studies of bushy cells also found considerable unit-to-unit variability in these response patterns. Here we present a population of models that can simulate the observed variation in GBCs. We used a simple coincidence detection model with an adaptive threshold and systematically varied its six parameters. Out of 567000 parameter combinations tested, 7520 primary-like-with-notch models and 4094 onset-L models were selected that satisfied a set of physiological criteria for a GBC unit. Analyses of the model parameters and output measures revealed that the parameters of the accepted model population are weakly correlated with each other to retain major GBC properties, and that the output spiking patterns of the model are affected by a combination of multiple parameters. Simulations of frequency-dependent temporal properties of the model GBCs showed a reasonable fit to empirical data, supporting the validity of our population modeling. The computational simplicity and efficiency of the model structure makes our approach suitable for future large-scale simulations of binaural information processing that may involve thousands of GBC units.

Expression of Na/K-ATPase subunits in the human cochlea: a confocal and super-resolution microscopy study with special reference to auditory nerve excitation and cochlear implantation.

Background: For the first time the expression of the ion transport protein sodium/potassium-ATPase and its isoforms was analyzed in the human cochlea using light- and confocal microscopy as well as super-resolution structured illumination microscopy. It may increase our understanding of its role in the propagation and processing of action potentials in the human auditory nerve and how electric nerve responses are elicited from auditory prostheses. Material and methods: Archival human cochlear sections were obtained from trans-cochlear surgeries. Antibodies against the Na/K-ATPase ß1 isoform together with α1 and α3 were used for immunohistochemistry. An algorithm was applied to assess the expression in various domains. Results: Na/K ATPase ß1 subunit was expressed, mostly combined with the α1 isoform. Neurons expressed the ß1 subunit combined with α3, while satellite glial cells expressed the α1 isoform without recognized association with ß1. Types I and II spiral ganglion neurons and efferent fibers expressed the Na/K-ATPase α3 subunit. Inner hair cells, nerve fibers underneath, and efferent and afferent fibers in the organ of Corti also expressed α1. The highest activity of Na/K-ATPase ß1 was at the inner hair cell/nerve junction and spiral prominence. Conclusion: The human auditory nerve displays distinct morphologic features represented in its molecular expression. It was found that electric signals generated via hair cells may not go uninterrupted across the spiral ganglion, but are locally processed. This may be related to particular filtering properties in the human acoustic pathway.

Cochlea and auditory nerve.

The transduction process in the cochlea requires patent hair cells. Population responses that reflect this patency are the cochlear microphonic (CM) and summating potential (SP). They can be measured using electrocochleography (ECochG). The CM reflects the sound waveform in the form of outer hair cell (OHC) depolarization and hyperpolarization, and the SP reflects the average voltage difference of the OHC membrane potential for depolarization and hyperpolarization. The CM can be measured using ECochG or via the so-called otoacoustic emissions, using a sensitive microphone in the ear canal. Neural population responses are called the compound action potentials (CAPs), which by frequency selective masking can be decomposed into narrow-band action potentials (NAPs) reflecting CAPs evoked by activity from small cochlear regions. Presence of CM and absence of CAPs are the diagnostic hallmarks of auditory neuropathy. Increased and prolonged SPs are often found in Ménière's disease but are too often in the normal range to be diagnostic. When including NAP waveforms, Ménière's disease can be differentiated from vestibular schwannomas, which often feature overlapping symptoms such as dizziness, hearing loss, and tinnitus. The patency of the efferent system, particularly the olivocochlear bundle, can be tested using the suppressive effect of contralateral stimulation on the otoacoustic emission amplitude.

The upper frequency limit for the use of phase locking to code temporal fine structure in humans: A compilation of viewpoints.

The relative importance of neural temporal and place coding in auditory perception is still a matter of much debate. The current article is a compilation of viewpoints from leading auditory psychophysicists and physiologists regarding the upper frequency limit for the use of neural phase locking to code temporal fine structure in humans. While phase locking is used for binaural processing up to about 1500 Hz, there is disagreement regarding the use of monaural phase-locking information at higher frequencies. Estimates of the general upper limit proposed by the contributors range from 1500 to 10000 Hz. The arguments depend on whether or not phase locking is needed to explain psychophysical discrimination performance at frequencies above 1500 Hz, and whether or not the phase-locked neural representation is sufficiently robust at these frequencies to provide useable information. The contributors suggest key experiments that may help to resolve this issue, and experimental findings that may cause them to change their minds. This issue is of crucial importance to our understanding of the neural basis of auditory perception in general, and of pitch perception in particular.

The effect of presentation level on spectrotemporal modulation detection.

The understanding of speech in noise relies (at least partially) on spectrotemporal modulation sensitivity. This sensitivity can be measured by spectral ripple tests, which can be administered at different presentation levels. However, it is not known how presentation level affects spectrotemporal modulation thresholds. In this work, we present behavioral data for normal-hearing adults which show that at higher ripple densities (2 and 4 ripples/oct), increasing presentation level led to worse discrimination thresholds. Results of a computational model suggested that the higher thresholds could be explained by a worsening of the spectrotemporal representation in the auditory nerve due to broadening of cochlear filters and neural activity saturation. Our results demonstrate the importance of taking presentation level into account when administering spectrotemporal modulation detection tests.

In Vivo Electrocochleography in Hybrid Cochlear Implant Users Implicates TMPRSS3 in Spiral Ganglion Function.

Cochlear implantation, a surgical method to bypass cochlear hair cells and directly stimulate the spiral ganglion, is the standard treatment for severe-to-profound hearing loss. Changes in cochlear implant electrode array design and surgical approach now allow for preservation of acoustic hearing in the implanted ear. Electrocochleography (ECochG) was performed in eight hearing preservation subjects to assess hair cell and neural function and elucidate underlying genetic hearing loss. Three subjects had pathogenic variants in TMPRSS3 and five had pathogenic variants in genes known to affect the cochlear sensory partition. The mechanism by which variants in TMPRSS3 cause genetic hearing loss is unknown. We used a 500-Hz tone burst to record ECochG responses from an intracochlear electrode. Responses consist of a cochlear microphonic (hair cell) and an auditory nerve neurophonic. Cochlear microphonics did not differ between groups. Auditory nerve neurophonics were smaller, on average, in subjects with TMPRSS3 deafness. Results of this proof-of-concept study provide evidence that pathogenic variants in TMPRSS3 may impact function of the spiral ganglion. While ECochG as a clinical and research tool has been around for decades, this study illustrates a new application of ECochG in the study of genetic hearing and deafness in vivo.

Olivocochlear efferents: Their action, effects, measurement and uses, and the impact of the new conception of cochlear mechanical responses.

The anatomy and physiology of olivocochlear (OC) efferents are reviewed. To help interpret these, recent advances in cochlear mechanics are also reviewed. Lateral OC (LOC) efferents innervate primary auditory-nerve (AN) fiber dendrites. The most important LOC function may be to reduce auditory neuropathy. Medial OC (MOC) efferents innervate the outer hair cells (OHCs) and act to turn down the gain of cochlear amplification. Cochlear amplification had been thought to act only through basilar membrane (BM) motion, but recent reports show that motion near the reticular lamina (RL) is amplified more than BM motion, and that RL-motion amplification extends to several octaves below the local characteristic frequency. Data on efferent effects on AN-fiber responses, otoacoustic emissions (OAEs) and human psychophysics are reviewed and reinterpreted in the light of the new cochlear-mechanical data. The possible origin of OAEs in RL motion is considered. MOC-effect measuring methods and MOC-induced changes in human responses are also reviewed, including that ipsilateral and contralateral sound can produce MOC effects with different patterns across frequency. MOC efferents help to reduce damage due to acoustic trauma. Many, but not all, reports show that subjects with stronger contralaterally-evoked MOC effects have better ability to detect signals (e.g. speech) in noise, and that MOC effects can be modulated by attention.

Complementary metrics of human auditory nerve function derived from compound action potentials.

Declines in auditory nerve (AN) function contribute to suprathreshold auditory processing and communication deficits in individuals with normal hearing, hearing loss, hyperacusis, and tinnitus. Procedures to characterize AN loss or dysfunction in humans are limited. We report several novel complementary metrics using the compound action potential (CAP), a direct measure of summated AN activity. Together, these metrics may be used to characterize AN function noninvasively in humans. We examined how these metrics change with stimulus intensity and interpreted these changes within a framework of known physiological properties of the basilar membrane and AN. Our results reveal how neural synchrony and the recruitment of AN fibers with longer first-spike latencies likely contribute to the CAP, affect auditory processing, and differ with noise exposure history in younger adults with normal pure-tone thresholds. Moving forward, this new battery of metrics provides a crucial step toward new diagnostics of AN function in humans. NEW & NOTEWORTHY Loss or inactivity of auditory nerve (AN) fibers is thought to contribute to suprathreshold auditory processing deficits, but evidence-based methods to assess these effects are not available. We describe several novel metrics that together may be used to quantify neural synchrony and characterize AN function in humans.

Analysis of a purely conductance-based stochastic nerve fibre model as applied to compound models of populations of human auditory nerve fibres used in cochlear implant simulations.

The study presents the application of a purely conductance-based stochastic nerve fibre model to human auditory nerve fibres within finite element volume conduction models of a semi-generic head and user-specific cochleae. The stochastic, threshold and temporal characteristics of the human model are compared and successfully validated against physiological feline results with the application of a mono-polar, bi-phasic, cathodic first stimulus. Stochastic characteristics validated include: (i) the log(Relative Spread) versus log(fibre diameter) distribution for the discharge probability versus stimulus intensity plots and (ii) the required exponential membrane noise versus transmembrane voltage distribution. Intra-user, and to a lesser degree inter-user, comparisons are made with respect to threshold and dynamic range at short and long pulse widths for full versus degenerate single fibres as well as for populations of degenerate fibres of a single user having distributed and aligned somas with varying and equal diameters. Temporal characteristics validated through application of different stimulus pulse rates and different stimulus intensities include: (i) discharge rate, latency and latency standard deviation versus stimulus intensity, (ii) period histograms and (iii) interspike interval histograms. Although the stochastic population model does not reduce the modelled single deterministic fibre threshold, the simulated stochastic and temporal characteristics show that it could be used in future studies to model user-specific temporally encoded information, which influences the speech perception of CI users.

The heterospecific calling song can improve conspecific signal detection in a bushcricket species.

In forest clearings of the Malaysian rainforest, chirping and trilling Mecopoda species often live in sympatry. We investigated whether a phenomenon known as stochastic resonance (SR) improved the ability of individuals to detect a low-frequent signal component typical of chirps when members of the heterospecific trilling species were simultaneously active. This phenomenon may explain the fact that the chirping species upholds entrainment to the conspecific song in the presence of the trill. Therefore, we evaluated the response probability of an ascending auditory neuron (TN-1) in individuals of the chirping Mecopoda species to triple-pulsed 2, 8 and 20 kHz signals that were broadcast 1 dB below the hearing threshold while increasing the intensity of either white noise or a typical triller song. Our results demonstrate the existence of SR over a rather broad range of signal-to-noise ratios (SNRs) of input signals when periodic 2 kHz and 20 kHz signals were presented at the same time as white noise. Using the chirp-specific 2 kHz signal as a stimulus, the maximum TN-1 response probability frequently exceeded the 50% threshold if the trill was broadcast simultaneously. Playback of an 8 kHz signal, a common frequency band component of the trill, yielded a similar result. Nevertheless, using the trill as a masker, the signal-related TN-1 spiking probability was rather variable. The variability on an individual level resulted from correlations between the phase relationship of the signal and syllables of the trill. For the first time, these results demonstrate the existence of SR in acoustically-communicating insects and suggest that the calling song of heterospecifics may facilitate the detection of a subthreshold signal component in certain situations. The results of the simulation of sound propagation in a computer model suggest a wide range of sender-receiver distances in which the triller can help to improve the detection of subthreshold signals in the chirping species.

Psychophysical and modeling approaches towards determining the cochlear phase response based on interaural time differences.

The cochlear phase response is often estimated by measuring masking of a tonal target by harmonic complexes with various phase curvatures. Maskers yielding most modulated internal envelope representations after passing the cochlear filter are thought to produce minimum masking, with fast-acting cochlear compression as the main contributor to that effect. Thus, in hearing-impaired (HI) listeners, reduced cochlear compression hampers estimation of the phase response using the masking method. This study proposes an alternative approach, based on the effect of the envelope modulation strength on the sensitivity to interaural time differences (ITDs). To evaluate the general approach, ITD thresholds were measured in seven normal-hearing listeners using 300-ms Schroeder-phase harmonic complexes with nine different phase curvatures. ITD thresholds tended to be lowest for phase curvatures roughly similar to those previously shown to produce minimum masking. However, an unexpected ITD threshold peak was consistently observed for a particular negative phase curvature. An auditory-nerve based ITD model predicted the general pattern of ITD thresholds except for the threshold peak, as well as published envelope ITD data. Model predictions simulating outer hair cell loss support the feasibility of the ITD-based approach to estimate the phase response in HI listeners.

Relationship Between Peripheral and Psychophysical Measures of Amplitude Modulation Detection in Cochlear Implant Users.

OBJECTIVE: This study investigates the relationship between electrophysiological and psychophysical measures of amplitude modulation (AM) detection. Prior studies have reported both measures of AM detection recorded separately from cochlear implant (CI) users and acutely deafened animals, but no study has made both measures in the same CI users. Animal studies suggest a progressive loss of high-frequency encoding as one ascends the auditory pathway from the auditory nerve to the cortex. Because the CI speech processor uses the envelope of an ongoing acoustic signal to modulate pulse trains that are subsequently delivered to the intracochlear electrodes, it is of interest to explore auditory nerve responses to modulated stimuli. In addition, psychophysical AM detection abilities have been correlated with speech perception outcomes. Thus, the goal was to explore how the auditory nerve responds to AM stimuli and to relate those physiologic measures to perception. DESIGN: Eight patients using Cochlear Ltd. Implants participated in this study. Electrically evoked compound action potentials (ECAPs) were recorded using a 4000 pps pulse train that was sinusoidally amplitude modulated at 125, 250, 500, and 1000 Hz rates. Responses were measured for each pulse over at least one modulation cycle for an apical, medial, and basal electrode. Psychophysical modulation detection thresholds (MDTs) were also measured via a three-alternative forced choice, two-down, one-up adaptive procedure using the same modulation frequencies and electrodes. RESULTS: ECAPs were recorded from individual pulses in the AM pulse train. ECAP amplitudes varied sinusoidally, reflecting the sinusoidal variation in the stimulus. A modulated response amplitude (MRA) metric was calculated as the difference in the maximal and minimum ECAP amplitudes over the modulation cycles. MRA increased as modulation frequency increased, with no apparent cutoff (up to 1000 Hz). In contrast, MDTs increased as the modulation frequency increased. This trend is inconsistent with the physiologic measures. For a fixed modulation frequency, correlations were observed between MDTs and MRAs; this trend was evident at all frequencies except 1000 Hz (although only statistically significant for 250 and 500 Hz AM rates), possibly an indication of central limitations in processing of high modulation frequencies. Finally, peripheral responses were larger and psychophysical thresholds were lower in the apical electrodes relative to basal and medial electrodes, which may reflect better cochlear health and neural survival evidenced by lower preoperative low-frequency audiometric thresholds and steeper growth of neural responses in ECAP amplitude growth functions for apical electrodes. CONCLUSIONS: Robust ECAPs were recorded for all modulation frequencies tested. ECAP amplitudes varied sinusoidally, reflecting the periodicity of the modulated stimuli. MRAs increased as the modulation frequency increased, a trend we attribute to neural adaptation. For low modulation frequencies, there are multiple current steps between the peak and valley of the modulation cycle, which means successive stimuli are more similar to one another and neural responses are more likely to adapt. Higher MRAs were correlated with lower psychophysical thresholds at low modulation frequencies but not at 1000 Hz, implying a central limitation to processing of modulated stimuli.

Fast Click Rate Electrocochleography and Auditory Brainstem Response in Normal-Hearing Adults Using Continuous Loop Averaging Deconvolution.

OBJECTIVES: Using the continuous loop averaging deconvolution (CLAD) technique for conventional electrocochleography (ECochG) and auditory brainstem response (ABR) recordings, the effects of testing at high stimulus rates may have the potential to diagnose disorders of the inner ear and auditory nerve. First, a body of normative data using the CLAD technique must be established. DESIGN: Extratympanic click ECochG and ABR to seven stimulus rates using CLAD were measured simultaneously from a tympanic membrane electrode and surface electrodes on the forehead and mastoid of 42 healthy individuals. RESULTS: Results showed that the compound action potential (AP) of the ECochG and waves I, III, and V of the ABR decreased in amplitude and increased in latency as stimulus rate was increased from standard 7.1 clicks/s up to 507.81 clicks/s, with sharp reduction in AP amplitude at 97.66 clicks/s and reaching asymptote at 292.97 clicks/s. The summating potential (SP) of the ECochG, however, stayed relatively stable, resulting in increased SP/AP ratios with increasing rate. The SP/AP amplitude ratio showed more stability than AP amplitude findings, thus it is recommended for use in evaluation of cochlear and neural response. CONCLUSIONS: Results of both amplitude and latency data from this normative neural adaptation function of the auditory pathway serves as guide for improving diagnostic utility of both ECochG and ABR using CLAD as a reliable technique in distinguishing inner ear and auditory nerve disorders.