Auditory Research publications

Mutations in COCH (coagulation factor C homology) are etiologic for the late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. We introduced the G88E mutation by gene targeting into the mouse and have created a Coch(G88E/G88E) mouse model for the study of DFNA9 pathogenesis and cochlin function. Vestibular-evoked potential (VsEP) thresholds of Coch(G88E/G88E) mice were elevated at all ages tested compared with wild-type littermates. At the oldest ages, two out of eight Coch(G88E/G88E) mice had no measurable VsEP. Auditory brainstem response (ABR) thresholds of Coch(G88E/G88E) mice were substantially elevated at 21 months but not at younger ages tested. At 21 months, four of eight Coch(G88E/G88E) mice had absent ABRs at all frequencies tested and two of three Coch(G88E)(/+) mice had absent ABRs at three of four frequencies tested. Distortion product otoacoustic emission amplitudes of Coch(G88E/G88E) mice were substantially lower than Coch(+/+) mice and absent in the same Coch(G88E/G88E) mice with absent ABRs. These results suggest that vestibular function is affected beginning as early as 11 months when cochlear function appears to be normal, and dysfunction increases with age. Hearing loss declines substantially at 21 months of age and progresses to profound hearing loss at some to all frequencies tested. This is the only mouse model developed to date where hearing loss begins at such an advanced age, providing an opportunity to study both progressive age-related hearing loss and possible interventional therapies.

A new subthreshold form of multisensory processing has been recently identified that results from the convergence of suprathreshold excitatory inputs from one modality with subthreshold inputs from another. Because of the subthreshold nature of the second modality, descriptive measures of sensory features such as receptive field properties or location are not directly apparent as they are for traditional bimodal neurons. This raises the question of whether or not subthreshold signals actually convey sensory-specific receptive field information as seen in their bimodal counterparts, or if they represent non-specific effects such as arousal. The present experiment addressed this issue in visually-responsive neurons from the cat posterolateral lateral suprasylvian cortex (PLLS). Single-unit electrophysiological techniques were used to record neuronal responses to visual, auditory and combined visual-auditory stimuli while the intensity of stimulation in the subthreshold auditory modality was systematically altered. The results showed that subthreshold multisensory neurons were sensitive to changes in auditory stimulus intensity. These receptive field sensitivities are similar to those observed in bimodal neurons and thereby represent sensory-specific, not arousal-related responses. In addition, these results provide further support for the notion that multisensory processing occurs along a dynamic continuum of neuronal convergence patterns from bimodal to purely sensory-specific.

Neurons responsive to visual stimulation have now been described in the auditory cortex of various species, but their functions are largely unknown. Here we investigate the auditory and visual spatial sensitivity of neurons recorded in 5 different primary and non-primary auditory cortical areas of the ferret. We quantified the spatial tuning of neurons by measuring the responses to stimuli presented across a range of azimuthal positions and calculating the mutual information (MI) between the neural responses and the location of the stimuli that elicited them. MI estimates of spatial tuning were calculated for unisensory visual, unisensory auditory and for spatially and temporally coincident auditory-visual stimulation. The majority of visually responsive units conveyed significant information about light-source location, whereas, over a corresponding region of space, acoustically responsive units generally transmitted less information about sound-source location. Spatial sensitivity for visual, auditory and bisensory stimulation was highest in the anterior dorsal field, the auditory area previously shown to be innervated by a region of extrastriate visual cortex thought to be concerned primarily with spatial processing, whereas the posterior pseudosylvian field and posterior suprasylvian field, whose principal visual input arises from cortical areas that appear to be part of the 'what' processing stream, conveyed less information about stimulus location. In some neurons, pairing visual and auditory stimuli led to an increase in the spatial information available relative to the most effective unisensory stimulus, whereas, in a smaller subpopulation, combined stimulation decreased the spatial MI. These data suggest that visual inputs to auditory cortex can enhance spatial processing in the presence of multisensory cues and could therefore potentially underlie visual influences on auditory localization.

Despite their prevalence in nature, echoes are not perceived as events separate from the sounds arriving directly from an active source, until the echo's delay is long. We measured the head-saccades of barn owls and the responses of neurons in their auditory space-maps while presenting a long duration noise-burst and a simulated echo. Under this paradigm, there were two possible stimulus segments that could potentially signal the location of the echo. One was at the onset of the echo; the other, after the offset of the direct (leading) sound, when only the echo was present. By lengthening the echo's duration, independently of its delay, spikes and saccades were evoked by the source of the echo even at delays that normally evoked saccades to only the direct source. An echo's location thus appears to be signaled by the neural response evoked after the offset of the direct sound.

This study examined the effect of signal-temporal uncertainty on detection of a 120-ms, 1-kHz tone in the presence of a continuous sequence of 120-ms bursts of either a broadband noise or a random-frequency, two-tone complex. Using the method of constant stimuli, signal-temporal uncertainty was defined as the difference in threshold across temporally uncertain and temporally defined listening conditions. Results indicted an average effect of signal-temporal uncertainty of 2dB for the noise masker compared to 9dB for the random-frequency, two-tone masker. These results suggest that signal-temporal uncertainty may be more detrimental for conditions in which informational masking dominates performance.

The medial nucleus of the trapezoid body (MNTB) receives excitatory input from giant presynaptic terminals, the calyces of Held. The MNTB functions as a sign inverter giving inhibitory input to the lateral and medial superior olive, where its input is important in the generation of binaural sensitivity to cues for sound localization. Extracellular recordings from MNTB neurons show complex spikes consisting of a prepotential, thought to reflect synaptic activation, followed by a postsynaptic action potential. This makes the synapse ideal to study synaptic transmission in vivo because presynaptic and postsynaptic activity can be monitored with a single electrode. Recent in vivo and in vitro studies have observed isolated prepotentials in the MNTB suggesting that, under certain stimulus conditions, synaptic transmission fails. We investigated synaptic transmission at the calyx of Held in the MNTB of the adult cat and concluded that synaptic transmission was completely secure in terms of rate of transmitted spikes. However, synaptic transmission was found to be less secure in terms of timing. With increasing spike rate, the synaptic delay showed an increase of up to 100 μs, as well as a decrease in amplitude of the action potential. This variability in delay is of a surprisingly high magnitude given the hypothesized role of these binaural circuits in sound localization and given the fact that this is one of the largest synapses in the mammalian brain.

Hypothesis: Intratympanic (IT) application of dexamethasone will reduce ototoxicity associated with systemic cisplatin therapy. Background: Cisplatin is a common chemotherapeutic drug often dose-limited by ototoxicity attributed to the formation of reactive oxygen and nitrogen species damaging critical inner ear structures. Steroids have been shown to reduce formation of reactive oxygen species and thus may reduce ototoxicity. In the present pilot study, we test this hypothesis by IT administration of dexamethasone in a novel murine model of cisplatin ototoxicity. Methods: Click- and pure-tone-evoked auditory brainstem responses (ABRs) in young CBA/J mice were measured. The first phase consisted of a dosing study to identify the optimal cisplatin dose for ototoxicity. In the next phase, ABR thresholds were measured in cisplatin-treated mice after 5 days of IT injection of 24 mg/ml of dexamethasone in 1 ear and normal saline in the opposite ear to serve as controls. Results: Intraperitoneal injection of 14 mg/kg of cisplatin induces significant hearing loss (click-evoked ABR threshold elevation = 12 +/- 7 dB, mu +/- standard error of the mean) with acceptable mortality (20%). The ears that received IT dexamethasone in cisplatin-treated mice had minimal ABR threshold shifts with the click, 8 and 16 kHz of stimuli. There was no significant difference between IT dexamethasone and IT saline ears at 32 kHz. Conclusion: IT dexamethasone protected the mouse ear against cisplatin-induced ototoxicity in a frequency-dependent manner. The present results suggest that IT dexamethasone may be a safe, simple, and effective intervention that minimizes cisplatin ototoxicity without interfering with the chemotherapeutic actions of cisplatin.

Objectives/Hypothesis: To test whether noise‐exposure, which activates a cochlear immune response with cytokine expression and infiltration of circulating leukocytes could augment the response to antigen (Ag). Study Design: Randomized, prospective, mice. Methods: We sensitized mice to an Ag, injected it intrathecally, and subsequently exposed the mice to noise (8–16 kHz, 90, 100, or 118 dB for 2 hours). Control mice received either noise exposure alone (100 or 118 dB), Ag challenge alone, intrathecal surgery and phosphate‐buffered saline injection or no treatment. Four hours or 7 days later the mice were killed and cochlear sections were evaluated immunohistochemically for CD45, ICAM‐1, and phospho‐nuclear transcription factor‐κB expression. Results: Intrathecal Ag injection caused no hearing loss, but did result in a small immune response. Loud noise (118 dB) caused severe hearing loss and slight inflammation. The number of CD45‐positive cells was significantly greater in the Ag plus‐118 dB noise group relative to the Ag‐alone group or 118 dB noise‐exposure group. ICAM expression was seen in the lower part of the spiral ligament and small vessels within the normal cochlea. The amount of expression increased after Ag injection and acoustic trauma. Activated nuclear transcription factor‐κB occurred in the nuclei of hair cells, supporting cells, spiral ligament fibrocytes, and neurons 4 hours after noise exposure. Conclusions: It seems that noise exposure can activate a cochlear immune response, which in the presence of Ag, allows for greater recruitment of inflammatory cells than occurred in response to Ag alone.

The influence of noise exposure on the parameters of a convolution model of the compound action potential (CAP) was examined. CAPs were recorded in normal-hearing gerbils and in gerbils exposed to a 117dBSPL 8kHz band of noise for various durations. The CAPs were fitted with an analytic CAP to obtain the parameters representing the number of nerve fibers (N), the probability density function [P(t)] from a population of nerve fibers, and the single-unit waveform [U(t)]. The results showed that the analytic CAP fitted the physiologic CAPs well with correlations of approximately 0.90. A subsequent analysis using hierarchical linear modeling quantified the change in the parameters as a function of both signal level and hearing threshold. The results showed that noise exposure caused some of the parameter-level functions to simply shift along the signal level axis in proportion to the amount of hearing loss, whereas others shifted along the signal level axis and steepened. Significant changes occurred in the U(t) parameters, but they were not related to hearing threshold. These results suggest that noise exposure alters the physiology underlying the CAP, some of which can be explained by a simple lack of gain, whereas others may not.

Schairer et al. [(2003). “Effects of peripheral nonlinearity on psychometric functions for forward-masked tones,” J. Acoust. Soc. Am. 133, 1560–1573] demonstrated that cochlear nonlinearity is reflected in psychometric-function (PF) slopes for 4 kHz forward-masked tones. The goals of the current study were to use PF slopes to compare the degree of compression between signal frequencies of 0.25 and 4 kHz in listeners with normal hearing (LNH), and between LNH and listeners with cochlear hearing loss (LHL). Forward-masked thresholds were estimated in LNH and LHL using on- and off-frequency maskers and 0.25 and 4 kHz signals in three experiments. PFs were reconstructed from adaptive-procedure data for each subject in each condition. Trends in PF slopes across conditions suggest comparable compression at 0.25 and 4 kHz, and potentially a wider bandwidth of compression in relative frequency at 0.25 kHz. This is consistent with other recent behavioral studies that revise earlier estimates of less compression at lower frequencies. The preliminary results in LHL demonstrate that PF slopes are abnormally steep at frequencies with HL, but are similar to those for LNH at frequencies with NH. Overall, the results are consistent with the notion that PF slopes reflect degree of cochlear nonlinearity and can be used as an additional measure of compression across frequency.

Neurons in the auditory midbrain are sensitive to differences in the timing of sounds at the two ears—an important sound localization cue. We used broadband noise stimuli to investigate the interaural-delay sensitivity of low-frequency neurons in two midbrain nuclei: the inferior colliculus (IC) and the dorsal nucleus of the lateral lemniscus. Noise-delay functions showed asymmetries not predicted from a linear dependence on interaural correlation: a stretching along the firing-rate dimension ( rate asymmetry), and a skewing along the interaural-delay dimension ( delay asymmetry). These asymmetries were produced by an envelope-sensitive component to the response that could not entirely be accounted for by monaural or binaural nonlinearities, instead indicating an enhancement of envelope sensitivity at or after the level of the superior olivary complex. In IC, the skew-like asymmetry was consistent with intermediate-type responses produced by the convergence of ipsilateral peak-type inputs and contralateral trough-type inputs. This suggests a stereotyped pattern of input to the IC. In the course of this analysis, we were also able to determine the contribution of time and phase components to neurons' internal delays. These findings have important consequences for the neural representation of interaural timing differences and interaural correlation—cues critical to the perception of acoustic space.

Purpose To clarify if large numbers of wide dynamic range compression channels provide advantages for vowel identification and to measure its acoustic effects. Methods Eight vowels produced by 12 talkers in the /hVd/ context were compressed using 1, 2, 4, 8, and 16 channels. Formant contrast indices (mean formant peak minus mean formant trough; maximum formant peak minus minimum formant trough) were developed to quantify spectral changes. Twenty listeners with mild to moderately severe sensorineural hearing loss identified the compressed vowels in an 8-alternative forced-choice procedure. Results Formant contrast measures revealed significant spectral flattening for 6 of the 8 vowels as channel number increased. A significant decrease in vowel identification performance was also observed as spectral contrast decreased. Conclusions Increasing the number of wide dynamic range compression channels may not be beneficial for all speech signals, and individual vowel identification performance can vary greatly for listeners with similar hearing loss.

Noise exposure is one of the most common causes of hearing loss. There is growing evidence suggesting that noise-induced peripheral hearing loss can also induce functional changes in the central auditory system. However, the physiological and biological changes in the central auditory system induced by noise exposure are poorly understood. To address these issues, neurophysiological recordings were made from the auditory cortex (AC) of awake rats using chronically implanted electrodes before and after acoustic overstimulation. In addition, focused gene microarrays and quantitative real-time polymerase chain reaction were used to identify changes in gene expression in the AC. Monaural noise exposure (120 dB sound pressure level, 1 h) significantly elevated hearing threshold on the exposed ear and induced a transient enhancement on the AC response amplitude 4 h after the noise exposure recorded from the unexposed ear. This increase of the cortical neural response amplitude was associated with an upregulation of genes encoding heat shock protein (HSP) 27 kDa and 70 kDa after several hours of the noise exposure. These results suggest that noise exposure can induce a fast physiological change in the AC which may be related to the changes of HSP expressions.

The newly-discovered tectal longitudinal column (TLC) spans the paramedian region of the mammalian tectum. It has connections with several nuclei of the auditory system. In this report, we provide the first detailed description of the responses of TLC neurons to auditory stimuli, including monaural and binaural tones and amplitude modulated tones. For comparison, responses in the inferior colliculus (IC) were also recorded. Neurons in the TLC were sensitive to similar ranges of frequency as IC neurons, could have comparably low thresholds, and showed primarily excitatory responses to stimulation of the contralateral ear with either phasic or sustained response patterns. Differences of TLC compared to IC neurons included broader frequency tuning, higher average threshold, longer response latencies, little synchronization or rate tuning to amplitude modulation frequency and a smaller degree of inhibition evoked by stimulation of the ipsilateral ear. These features of TLC neurons suggest a role for the TLC in descending auditory pathways.

Sensory systems adapt their neural code to changes in the sensory environment, often on multiple time scales. Here, we report a new form of adaptation in a first-order auditory interneuron (AN2) of crickets. We characterize the response of the AN2 neuron to amplitude-modulated sound stimuli and find that adaptation shifts the stimulus-response curves toward higher stimulus intensities, with a time constant of 1.5 s for adaptation and recovery. The spike responses were thus reduced for low-intensity sounds. We then address the question whether adaptation leads to an improvement of the signal's representation and compare the experimental results with the predictions of two competing hypotheses: infomax, which predicts that information conveyed about the entire signal range should be maximized, and selective coding, which predicts that "foreground" signals should be enhanced while "background" signals should be selectively suppressed. We test how adaptation changes the input-response curve when presenting signals with two or three peaks in their amplitude distributions, for which selective coding and infomax predict conflicting changes. By means of Bayesian data analysis, we quantify the shifts of the measured response curves and also find a slight reduction of their slopes. These decreases in slopes are smaller, and the absolute response thresholds are higher than those predicted by infomax. Most remarkably, and in contrast to the infomax principle, adaptation actually reduces the amount of encoded information when considering the whole range of input signals. The response curve changes are also not consistent with the selective coding hypothesis, because the amount of information conveyed about the loudest part of the signal does not increase as predicted but remains nearly constant. Less information is transmitted about signals with lower intensity.

Neurons selective for frequency modulated (FM) sweeps are common in auditory systems across different vertebrate groups and may underlie representation of species-specific vocalizations. Studies on mechanisms of FM sweep selectivity have primarily focused on sideband inhibition. Here, we present the first evidence for facilitatory mechanisms of FM sweep selectivity. Facilitatory interactions were found in 46 of 264 (17%) neurons tuned in the echolocation range (25–60 kHz) in the auditory cortex of the pallid bat. These neurons respond poorly to individual tones but are facilitated by combinations of tones with specific spectral and temporal intervals. Facilitation neurons show remarkable sensitivity to sub-millisecond differences in time delays between the two tones. Interestingly, the range of delays eliciting facilitation is not fixed but varies systematically with frequency difference between the two tones. Properties of facilitation strongly predict selectivity for the direction and rate of FM sweeps. Together with previous studies, there appear to be at least three mechanisms underlying FM rate and direction selectivity: sideband inhibition, duration tuning, and facilitation. Interestingly, similar mechanisms underlie direction and velocity tuning in the visual system, suggesting the evolution of similar computations across sensory systems to process dynamic sensory stimuli.

This study examined the costs of simultaneously monitoring two frequency regions. Listeners detected low- and high-frequency tones in a 2I4AFC procedure. On every trial, each signal was presented in either the first or second interval independently. Comparison of thresholds in single- and dual-signal conditions provided an estimate of the costs. Thresholds were obtained in quiet, in notched-filtered noise, and in randomized multitone maskers. No cost was found in quiet, whereas large costs were found for the masked conditions, especially for the multitone masker. These results suggest that costs of dividing attention in frequency depend on both signal and nonsignal channels.

Auditory neurons are likely adapted to process complex stimuli, such as vocalizations, which contain spectrotemporal modulations. However, basic properties of auditory neurons are often derived from tone pips presented in isolation, which lack spectrotemporal modulations. In this context, it is unclear how to deduce the functional role of auditory neurons from their tone pip-derived tuning properties. In this study, spectrotemporal receptive fields (STRFs) were obtained from responses to multi-tone stimulus ensembles differing in their average spectrotemporal density (i.e., number of tone pips per second). STRFs for different stimulus densities were derived from multiple single-unit activity (MUA) and local field potentials (LFPs), simultaneously recorded in primary auditory cortex of cats. Consistent with earlier studies, we found that the spectral bandwidth was narrower for MUA compared with LFPs. Both neural firing rate and LFP amplitude were reduced when the density of the stimulus ensemble increased. Surprisingly, we found that increasing the spectrotemporal sound density revealed with increasing clarity an over-representation of response peaks at frequencies of ∼3, 5, 10, and 20 kHz, in both MUA- and LFP-derived STRFs. Although the decrease in spectral bandwidth and neural activity with increasing stimulus density can likely be accounted for by forward suppression, the mechanisms underlying the over-representation of the octave-spaced response peaks are unclear. Plausibly, the over-representation may be a functional correlate of the periodic pattern of corticocortical connections observed along the tonotopic axis of cat auditory cortex.

In complex scenes, the identity of an auditory object can build up across seconds. Given that attention operates on perceptual objects, this perceptual buildup may alter the efficacy of selective auditory attention over time. Here, we measured identification of a sequence of spoken target digits presented with distracter digits from other directions to investigate the dynamics of selective attention. Performance was better when the target location was fixed rather than changing between digits, even when listeners were cued as much as 1 s in advance about the position of each subsequent digit. Spatial continuity not only avoided well known costs associated with switching the focus of spatial attention, but also produced refinements in the spatial selectivity of attention across time. Continuity of target voice further enhanced this buildup of selective attention. Results suggest that when attention is sustained on one auditory object within a complex scene, attentional selectivity improves over time. Similar effects may come into play when attention is sustained on an object in a complex visual scene, especially in cases where visual object formation requires sustained attention.

Objectives/Hypothesis: The cochlear amplifier is required for the exquisite sensitivity of mammalian hearing. Outer hair cells underlie the cochlear amplifier and they are unique in that they maintain an intracellular turgor pressure. Changing the turgor pressure of an isolated outer hair cells through osmotic challenge modulates its ability to produce electromotile force. We sought to determine the effect of osmotic challenge on cochlear function. Study Design: In vivo animal study. Methods: Hypotonic and hypertonic artificial perilymph was perfused through the scala tympani of anesthetized guinea pigs. Cochlear function was assessed by measuring the compound action potential, distortion product otoacoustic emissions, the cochlear microphonic, and the endocochlear potential. Results: Hypotonic perilymph decreased and hypertonic perilymph increased compound action potential and distortion product otoacoustic emission thresholds in a dose‐dependent and reversible manner. The cochlear microphonic quadratic distortion product magnitude increased after hypotonic perfusion and decreased with hypertonic perfusion. There were no changes in the stimulus intensity growth curve of the low‐frequency cochlear microphonic. The endocochlear potential was not affected by perilymph osmolality. Conclusions: These data demonstrate that perilymph osmolality can modulate cochlear function and are consistent with what would be expected if outer hair cells turgor pressure changes the gain of the cochlear amplifier in vivo.