Evidence That Ultrafast Nonquantal Transmission Underlies Synchronized Vestibular Action Potential Generation.

Amniotes evolved a unique postsynaptic terminal in the inner ear vestibular organs called the calyx that receives both quantal and nonquantal (NQ) synaptic inputs from Type I sensory hair cells. The nonquantal synaptic current includes an ultrafast component that has been hypothesized to underlie the exceptionally high synchronization index (vector strength) of vestibular afferent neurons in response to sound and vibration. Here, we present three lines of evidence supporting the hypothesis that nonquantal transmission is responsible for synchronized vestibular action potentials of short latency in the guinea pig utricle of either sex. First, synchronized vestibular nerve responses are unchanged after administration of the AMPA receptor antagonist CNQX, while auditory nerve responses are completely abolished. Second, stimulus evoked vestibular nerve compound action potentials (vCAP) are shown to occur without measurable synaptic delay and three times shorter than the latency of auditory nerve compound action potentials (cCAP), relative to the generation of extracellular receptor potentials. Third, paired-pulse stimuli designed to deplete the readily releasable pool (RRP) of synaptic vesicles in hair cells reveal forward masking in guinea pig auditory cCAPs, but a complete lack of forward masking in vestibular vCAPs. Results support the conclusion that the fast component of nonquantal transmission at calyceal synapses is indefatigable and responsible for ultrafast responses of vestibular organs evoked by transient stimuli.SIGNIFICANCE STATEMENT The mammalian vestibular system drives some of the fastest reflex pathways in the nervous system, ensuring stable gaze and postural control for locomotion on land. To achieve this, terrestrial amniotes evolved a large, unique calyx afferent terminal which completely envelopes one or more presynaptic vestibular hair cells, which transmits mechanosensory signals mediated by quantal and nonquantal (NQ) synaptic transmission. We present several lines of evidence in the guinea pig which reveals the most sensitive vestibular afferents are remarkably fast, much faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that demonstrates this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from Type I hair cells to their calyx partners.

Understanding degraded speech leads to perceptual gating of a brainstem reflex in human listeners.

The ability to navigate "cocktail party" situations by focusing on sounds of interest over irrelevant, background sounds is often considered in terms of cortical mechanisms. However, subcortical circuits such as the pathway underlying the medial olivocochlear (MOC) reflex modulate the activity of the inner ear itself, supporting the extraction of salient features from auditory scene prior to any cortical processing. To understand the contribution of auditory subcortical nuclei and the cochlea in complex listening tasks, we made physiological recordings along the auditory pathway while listeners engaged in detecting non(sense) words in lists of words. Both naturally spoken and intrinsically noisy, vocoded speech-filtering that mimics processing by a cochlear implant (CI)-significantly activated the MOC reflex, but this was not the case for speech in background noise, which more engaged midbrain and cortical resources. A model of the initial stages of auditory processing reproduced specific effects of each form of speech degradation, providing a rationale for goal-directed gating of the MOC reflex based on enhancing the representation of the energy envelope of the acoustic waveform. Our data reveal the coexistence of 2 strategies in the auditory system that may facilitate speech understanding in situations where the signal is either intrinsically degraded or masked by extrinsic acoustic energy. Whereas intrinsically degraded streams recruit the MOC reflex to improve representation of speech cues peripherally, extrinsically masked streams rely more on higher auditory centres to denoise signals.

The Benefits of Cochlear Implantation for Adults: A Systematic Umbrella Review.

OBJECTIVES: The uptake of cochlear implants among adults who could benefit (based on pure-tone audiometry) in developed countries is estimated to be less than 10%. Concerns about potential surgical complications, fear of losing residual hearing, and limited awareness about the benefits of this intervention contribute to the low adoption rate. To enhance quality of life and improve the uptake of cochlear implants, it is essential to have a clear understanding of their benefits. DESIGN: This umbrella review aims to summarize the major benefits of cochlear implant usage in adults, by synthesizing findings from published review articles. A comprehensive search of databases including MEDLINE, EMBASE, PsycINFO, and Google Scholar, was conducted. The search was limited to English-language review articles published between 1990 and 2022, focusing on cochlear implant outcomes in at least 5 adults (aged ≥18 years). Two independent reviewers screened titles, abstracts, and full-text articles, and conducted a quality assessment using the Joanna Briggs Checklist for Systematic Reviews and Research Syntheses. RESULTS: Forty-two articles were included in this review. There were 15 systematic reviews with meta-analysis, 25 systematic reviews without meta-analysis, and 2 systematic scoping reviews. All 42 articles underwent quality assessment using the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses, of which 40% (n = 17) satisfied 9 out of 11 quality criteria. This umbrella review shows that cochlear implants are associated with improvements in speech perception and recognition as well as improved quality of life and cognition. These benefits are observed in a significant proportion of adults undergoing the procedure, highlighting its effectiveness as a viable intervention for individuals with severe to profound hearing loss. CONCLUSIONS: The potential benefits of cochlear implantation appear to outweigh the risks and complications associated with the procedure. It is recommended that adults with severe to profound hearing loss in particular, engage in informed discussions with healthcare professionals to consider cochlear implantation as a viable treatment option.

Cross-modal functional connectivity supports speech understanding in cochlear implant users.

Sensory deprivation can lead to cross-modal cortical changes, whereby sensory brain regions deprived of input may be recruited to perform atypical function. Enhanced cross-modal responses to visual stimuli observed in auditory cortex of postlingually deaf cochlear implant (CI) users are hypothesized to reflect increased activation of cortical language regions, but it is unclear if this cross-modal activity is "adaptive" or "mal-adaptive" for speech understanding. To determine if increased activation of language regions is correlated with better speech understanding in CI users, we assessed task-related activation and functional connectivity of auditory and visual cortices to auditory and visual speech and non-speech stimuli in CI users (n = 14) and normal-hearing listeners (n = 17) and used functional near-infrared spectroscopy to measure hemodynamic responses. We used visually presented speech and non-speech to investigate neural processes related to linguistic content and observed that CI users show beneficial cross-modal effects. Specifically, an increase in connectivity between the left auditory and visual cortices-presumed primary sites of cortical language processing-was positively correlated with CI users' abilities to understand speech in background noise. Cross-modal activity in auditory cortex of postlingually deaf CI users may reflect adaptive activity of a distributed, multimodal speech network, recruited to enhance speech understanding.

Echocardiographic Findings in Critically Ill COVID-19 Patients Treated With and Without Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe echocardiographic findings among mechanically ventilated patients with COVID-19 acute respiratory distress syndrome, comparing those with and without venovenous extracorporeal membrane oxygenation (VV ECMO) support. DESIGN: Single-center, retrospective cohort study. SETTING: Intensive care unit (ICU) of a quaternary academic center. PARTICIPANTS: Patients with COVID-19 admitted between March 2020 and June 2021 receiving mechanical ventilation, with an echocardiogram within 72 hours of admission. INTERVENTIONS: Admission and follow-up echocardiograms during ICU stay. MEASUREMENTS: Patient characteristics and echocardiographic findings were analyzed. Mortality odds ratio (OR) for right ventricular (RV) systolic dysfunction and acute cor pulmonale (ACP) was calculated. MAIN RESULTS: Among 242 patients, 145 (60%) received VV ECMO. Median (IQR) PaO2/FiO2 was 76 (65-95) and 98 (85-140) in ECMO and non-ECMO patients, respectively (p ≤ 0.001). Initial echocardiograms showed no significant differences in left ventricular systolic dysfunction (10% v 15 %, p = 0.31) and RV systolic dysfunction (38% v. 27%, p = 0.27) between ECMO and non-ECMO patients. ACP was more frequent in the ECMO group at baseline (41% v. 26 %, p = 0.02). During the ICU stay, patients on ECMO exhibited a higher prevalence of RV systolic dysfunction (55% v 34%, p = 0.001) and ACP (51% v 26%, p = 0.002). RV systolic dysfunction (OR 1.99; 95% CI 1.09-3.63) and ACP (OR 2.95; 95% CI 1.55-5.62) on the follow-up echocardiograms were associated with higher odds of ICU mortality. CONCLUSIONS: The prevalence of echocardiographic abnormalities, in particular RV dysfunction, was frequent among patients with COVID-19 receiving VV ECMO support and was associated with worse clinical outcomes.

Cortical haemodynamic responses predict individual ability to recognise vocal emotions with uninformative pitch cues but do not distinguish different emotions.

We investigated the cortical representation of emotional prosody in normal-hearing listeners using functional near-infrared spectroscopy (fNIRS) and behavioural assessments. Consistent with previous reports, listeners relied most heavily on F0 cues when recognizing emotion cues; performance was relatively poor-and highly variable between listeners-when only intensity and speech-rate cues were available. Using fNIRS to image cortical activity to speech utterances containing natural and reduced prosodic cues, we found right superior temporal gyrus (STG) to be most sensitive to emotional prosody, but no emotion-specific cortical activations, suggesting that while fNIRS might be suited to investigating cortical mechanisms supporting speech processing it is less suited to investigating cortical haemodynamic responses to individual vocal emotions. Manipulating emotional speech to render F0 cues less informative, we found the amplitude of the haemodynamic response in right STG to be significantly correlated with listeners' abilities to recognise vocal emotions with uninformative F0 cues. Specifically, listeners more able to assign emotions to speech with degraded F0 cues showed lower haemodynamic responses to these degraded signals. This suggests a potential objective measure of behavioural sensitivity to vocal emotions that might benefit neurodiverse populations less sensitive to emotional prosody or hearing-impaired listeners, many of whom rely on listening technologies such as hearing aids and cochlear implants-neither of which restore, and often further degrade, the F0 cues essential to parsing emotional prosody conveyed in speech.

External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.

BACKGROUND: Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa. METHODS: An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days. RESULTS: Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage. CONCLUSION: No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.

Associations between intake of dietary flavonoids and the 10-year incidence of tinnitus in older adults.

PURPOSE: Dietary flavonoids are bioactive compounds that have been widely investigated for their associations with vascular health outcomes. As the development of tinnitus has been linked to vascular pathways, dietary flavonoids may have role in the prevention of tinnitus symptoms. This study reports the associations between the intakes of major classes of dietary flavonoids and 10-year incidence of tinnitus. METHODS: Of the 1753 participants (aged ≥ 50 years) from the Blue Mountains Hearing Study with complete baseline data on tinnitus symptoms and dietary intakes, 536 (31%) cases of tinnitus were identified and excluded from further analysis. Dietary data was collected using a semi-quantitative food frequency questionnaire and intakes of the five major classes of flavonoids were determined using U.S. Department of Agriculture flavonoid databases. Presence of prolonged tinnitus was assessed by a positive response to a single question administered by an audiologist. RESULTS: Of the remaining 1217 participants without tinnitus at baseline, 222 (18%) incident cases of tinnitus were identified over 10 years. After age-sex adjustment, participants in the third versus first quartile of proanthocyanidin intake were significantly less likely to develop incident tinnitus by 36% (HR = 0.64; 95% CI 0.43-0.96, Ptrend = 0.04). Following multivariable adjustment, this protective trend was non-significant (HR = 0.60; 95% CI 0.39-0.92; Ptrend = 0.06). Similarly, a non-significant protective trend was observed when comparing the fourth versus first quartile of intake of all flavonoids (OR = 0.61; 95% CI 0.39-0.96). No other associations were observed. CONCLUSION: Our findings do not support the hypothesis that dietary flavonoids are protective against the development of tinnitus over 10 years. The weak significant association observed between proanthocyanidin and incident tinnitus may be a chance finding as there was no significant trend following multivariate adjustments and, therefore, requires further studies to investigate these associations.

The influence of envelope shape on the lateralization of amplitude-modulated, low-frequency sound.

For abruptly gated sound, interaural time difference (ITD) cues at onset carry greater perceptual weight than those following. This research explored how envelope shape influences such carrier ITD weighting. Experiment 1 assessed the perceived lateralization of a tonal binaural beat that transitioned through ITD (diotic envelope, mean carrier frequency of 500 Hz). Listeners' left/right lateralization judgments were compared to those for static-ITD tones. For an 8 Hz sinusoidally amplitude-modulated envelope, ITD cues 24 ms after onset well-predicted reported sidedness. For an equivalent-duration "abrupt" envelope, which was unmodulated besides 20-ms onset/offset ramps, reported sidedness corresponded to ITDs near onset (e.g., 6 ms). However, unlike for sinusoidal amplitude modulation, ITDs toward offset seemingly also influenced perceived sidedness. Experiment 2 adjusted the duration of the offset ramp (25-75 ms) and found evidence for such offset weighting only for the most abrupt ramp tested. In experiment 3, an ITD was imposed on a brief segment of otherwise diotic filtered noise. Listeners discriminated right- from left-leading ITDs. In sinusoidal amplitude modulation, thresholds were lowest when the ITD segment occurred during rising amplitude. For the abrupt envelope, the lowest thresholds were observed when the segment occurred at either onset or offset. These experiments demonstrate the influence of envelope profile on carrier ITD sensitivity.

Estimating the perceptual weighting of interaural time difference cues in amplitude modulated binaural beats.

For an abruptly gated sound, perceived lateralization is determined primarily by binaural cues at onset. Relatively less is known about the temporal weighing of binaural cues-such as interaural time difference (ITD)-during more naturalistic modulation profiles. Here, an experiment measured the lateralization of a tonal binaural beat modulated by a diotic, 8-Hz sinusoidal amplitude modulation. Binaural beat lateralization (left/right, two alternatives) was compared to that for tones with static ITDs. Across three mean carrier frequencies (200, 500, and 800 Hz), ITDs occurring during early rising amplitude (e.g., 20-25 ms after onset) predicted the perceived lateralization of the binaural beat signals well.

A common periodic representation of interaural time differences in mammalian cortex.

Binaural hearing, the ability to detect small differences in the timing and level of sounds at the two ears, underpins the ability to localize sound sources along the horizontal plane, and is important for decoding complex spatial listening environments into separate objects - a critical factor in 'cocktail-party listening'. For human listeners, the most important spatial cue is the interaural time difference (ITD). Despite many decades of neurophysiological investigations of ITD sensitivity in small mammals, and computational models aimed at accounting for human perception, a lack of concordance between these studies has hampered our understanding of how the human brain represents and processes ITDs. Further, neural coding of spatial cues might depend on factors such as head-size or hearing range, which differ considerably between humans and commonly used experimental animals. Here, using magnetoencephalography (MEG) in human listeners, and electro-corticography (ECoG) recordings in guinea pig-a small mammal representative of a range of animals in which ITD coding has been assessed at the level of single-neuron recordings-we tested whether processing of ITDs in human auditory cortex accords with a frequency-dependent periodic code of ITD reported in small mammals, or whether alternative or additional processing stages implemented in psychoacoustic models of human binaural hearing must be assumed. Our data were well accounted for by a model consisting of periodically tuned ITD-detectors, and were highly consistent across the two species. The results suggest that the representation of ITD in human auditory cortex is similar to that found in other mammalian species, a representation in which neural responses to ITD are determined by phase differences relative to sound frequency rather than, for instance, the range of ITDs permitted by head size or the absolute magnitude or direction of ITD.

Mechanisms of sound localization in mammals.

The ability to determine the location of a sound source is fundamental to hearing. However, auditory space is not represented in any systematic manner on the basilar membrane of the cochlea, the sensory surface of the receptor organ for hearing. Understanding the means by which sensitivity to spatial cues is computed in central neurons can therefore contribute to our understanding of the basic nature of complex neural representations. We review recent evidence concerning the nature of the neural representation of auditory space in the mammalian brain and elaborate on recent advances in the understanding of mammalian subcortical processing of auditory spatial cues that challenge the "textbook" version of sound localization, in particular brain mechanisms contributing to binaural hearing.

Influence of envelope waveform on ITD sensitivity of neurons in the auditory midbrain.

Interaural time differences (ITDs) conveyed by the modulated envelopes of high-frequency sounds can serve as a cue for localizing a sound source. Klein-Hennig et al. (J Acoust Soc Am 129: 3856, 2011) demonstrated the envelope attack (the rate at which stimulus energy in the envelope increases) and the duration of the pause (the interval between successive envelope pulses) as important factors affecting sensitivity to envelope ITDs in human listeners. Modulated sounds with rapid attacks and long pauses produce the lowest ITD discrimination thresholds. The duration of the envelope's sustained component (sustain) and the rate at which stimulus energy falls at the offset of the envelope (decay) are only minor factors. We assessed the responses of 71 single neurons, recorded from the midbrains of 15 urethane-anesthetized tri-colored guinea pigs, to envelope shapes in which the four envelope components, i.e., attack, sustain, decay, and pause, were systematically varied. We confirmed the importance of the attack and pause components in generating ITD-sensitive responses. Analysis of neural firing rates demonstrated more neurons (49/71) show ITD sensitivity in response to "damped" stimuli (fast attack and slow decay) compared with "ramped" stimuli (slow attack and fast decay) (14/71). Furthermore, the lowest threshold for the damped stimulus (91 µs) was lower by a factor of 4 than that for the temporally reversed ramped envelope shape (407 µs). The data confirm the importance of fast attacks and optimal pause durations in generating sensitivity to ITDs conveyed in the modulated envelopes of high-frequency sounds and are incompatible with models of ITD processing based on the integration of sound energy over time.NEW & NOTEWORTHY Using single-neuron electrophysiology, we show that the precise shape of a sound's "energy envelope" is a critical factor in determining how well midbrain neurons are able to convey information about auditory spatial cues. Consistent with human behavioral performance, sounds with rapidly rising energy and relatively long intervals between energy bursts are best at conveying spatial information. The data suggest specific sound energy patterns that might best be applied to hearing devices to aid spatial listening.

Subthreshold resonance properties contribute to the efficient coding of auditory spatial cues.

Neurons in the medial superior olive (MSO) and lateral superior olive (LSO) of the auditory brainstem code for sound-source location in the horizontal plane, extracting interaural time differences (ITDs) from the stimulus fine structure and interaural level differences (ILDs) from the stimulus envelope. Here, we demonstrate a postsynaptic gradient in temporal processing properties across the presumed tonotopic axis; neurons in the MSO and the low-frequency limb of the LSO exhibit fast intrinsic electrical resonances and low input impedances, consistent with their processing of ITDs in the temporal fine structure. Neurons in the high-frequency limb of the LSO show low-pass electrical properties, indicating they are better suited to extracting information from the slower, modulated envelopes of sounds. Using a modeling approach, we assess ITD and ILD sensitivity of the neural filters to natural sounds, demonstrating that the transformation in temporal processing along the tonotopic axis contributes to efficient extraction of auditory spatial cues.

Differences in the temporal course of interaural time difference sensitivity between acoustic and electric hearing in amplitude modulated stimuli.

Previous studies have shown that normal-hearing (NH) listeners' spatial perception of non-stationary interaural time differences (ITDs) is dominated by the carrier ITD during rising amplitude segments. Here, ITD sensitivity throughout the amplitude-modulation cycle in NH listeners and bilateral cochlear implant (CI) subjects is compared, the latter by means of direct stimulation of a single electrode pair. The data indicate that, while NH listeners are most sensitive to ITDs applied toward the beginning of a modulation cycle at 600 Hz, NH listeners at 200 Hz and especially bilateral CI subjects at 200 pulses per second (pps) are more sensitive to ITDs applied to the modulation maximum. This has implications for spatial-hearing in complex environments: NH listeners' dominant 600-Hz ITD information from the rising amplitude segments comprises direct sound information. The 200-pps low rate required to get ITD sensitivity in CI users results in a higher weight of pulses later in the modulation cycle where the source ITDs are more likely corrupted by reflections. This indirectly indicates that even if future binaural CI processors are able to provide perceptually exploitable ITD information, CI users will likely not get the full benefit from such pulse-based ITD cues in reverberant and other complex environments.

Phosphoinositide Modulation of Heteromeric Kv1 Channels Adjusts Output of Spiral Ganglion Neurons from Hearing Mice.

Spiral ganglion neurons (SGNs) relay acoustic code from cochlear hair cells to the brainstem, and their stimulation enables electrical hearing via cochlear implants. Rapid adaptation, a mechanism that preserves temporal precision, and a prominent feature of auditory neurons, is regulated via dendrotoxin-sensitive low-threshold voltage-activated (LVA) K(+) channels. Here, we investigated the molecular physiology of LVA currents in SGNs cultured from mice following the onset of hearing (postnatal days 12-21). Kv1.1- and Kv1.2-specific toxins blocked the LVA currents in a comparable manner, suggesting that both subunits contribute to functional heteromeric channels. Confocal immunofluorescence in fixed cochlear sections localized both Kv1.1 and Kv1.2 subunits to specific neuronal microdomains, including the somatic membrane, juxtaparanodes, and the first heminode, which forms the spike initiation site of the auditory nerve. The spatial distribution of Kv1 immunofluorescence appeared mutually exclusive to that of Kv3.1b subunits, which mediate high-threshold voltage-activated currents. As Kv1.2-containing channels are positively modulated by membrane phosphoinositides, we investigated the influence of phosphatidylinositol-4,5-bisphosphate (PIP2) availability on SGN electrophysiology. Reducing PIP2 production using wortmannin, or sequestration of PIP2 using a palmitoylated peptide (PIP2-PP), slowed adaptation rate in SGN populations. PIP2-PP specifically inhibited the LVA current in SGNs, an effect reduced by intracellular dialysis of a nonhydrolysable analog of PIP2. PIP2-PP also inhibited heterologously expressed Kv1.1/Kv1.2 channels, recapitulating its effect in SGNs. Collectively, the data identify Kv1.1/Kv1.2 heteromeric channels as key regulators of action potential initiation and propagation in the auditory nerve, and suggest that modulation of these channels by endogenous phosphoinositides provides local control of membrane excitability. SIGNIFICANCE STATEMENT: Rapid spike adaptation is an important feature of auditory neurons that preserves temporal precision. In spiral ganglion neurons, the primary afferents in the cochlea, adaptation is regulated by heteromeric ion channels composed of Kv1.1 and Kv1.2 subunits. These subunits colocalize to common functional microdomains, such as juxtaparanodes and the somatic membrane. Activity of the heteromeric channels is controlled by cellular availability of PIP2, a membrane phospholipid. This mechanism provides an intrinsic regulation of output from the auditory nerve, which could be targeted for therapeutic adjustment of hearing sensitivity.

Objective Measures of Neural Processing of Interaural Time Differences.

We assessed neural sensitivity to interaural time differences (ITDs) conveyed in the temporal fine structure (TFS) of low-frequency sounds and ITDs conveyed in the temporal envelope of amplitude-modulated (AM'ed) high-frequency sounds. Using electroencephalography (EEG), we recorded brain activity to sounds in which the interaural phase difference (IPD) of the TFS (or the modulated temporal envelope) was repeatedly switched between leading in one ear or the other. When the amplitude of the tones is modulated equally in the two ears at 41 Hz, the interaural phase modulation (IPM) evokes an IPM following-response (IPM-FR) in the EEG signal. For low-frequency signals, IPM-FRs were reliably obtained, and largest for an IPM rate of 6.8 Hz and when IPD switches (around 0°) were in the range 45-90°. IPDs conveyed in envelope of high-frequency tones also generated IPM-FRs; response maxima occurred for IPDs switched between 0° and 180° IPD. This is consistent with the interpretation that distinct binaural mechanisms generate the IPM-FR at low and high frequencies, and with the reported physiological responses of medial superior olive (MSO) and lateral superior olive (LSO) neurons in other mammals. Low-frequency binaural neurons in the MSO are considered maximally activated by IPDs in the range 45-90°, consistent with their reception of excitatory inputs from both ears. High-frequency neurons in the LSO receive excitatory and inhibitory input from the two ears receptively--as such maximum activity occurs when the sounds at the two ears are presented out of phase.

Emphasis of spatial cues in the temporal fine structure during the rising segments of amplitude-modulated sounds.

The ability to locate the direction of a target sound in a background of competing sources is critical to the survival of many species and important for human communication. Nevertheless, brain mechanisms that provide for such accurate localization abilities remain poorly understood. In particular, it remains unclear how the auditory brain is able to extract reliable spatial information directly from the source when competing sounds and reflections dominate all but the earliest moments of the sound wave reaching each ear. We developed a stimulus mimicking the mutual relationship of sound amplitude and binaural cues, characteristic to reverberant speech. This stimulus, named amplitude modulated binaural beat, allows for a parametric and isolated change of modulation frequency and phase relations. Employing magnetoencephalography and psychoacoustics it is demonstrated that the auditory brain uses binaural information in the stimulus fine structure only during the rising portion of each modulation cycle, rendering spatial information recoverable in an otherwise unlocalizable sound. The data suggest that amplitude modulation provides a means of "glimpsing" low-frequency spatial cues in a manner that benefits listening in noisy or reverberant environments.

Selective adaptation to "oddball" sounds by the human auditory system.

Adaptation to both common and rare sounds has been independently reported in neurophysiological studies using probabilistic stimulus paradigms in small mammals. However, the apparent sensitivity of the mammalian auditory system to the statistics of incoming sound has not yet been generalized to task-related human auditory perception. Here, we show that human listeners selectively adapt to novel sounds within scenes unfolding over minutes. Listeners' performance in an auditory discrimination task remains steady for the most common elements within the scene but, after the first minute, performance improves for distinct and rare (oddball) sound elements, at the expense of rare sounds that are relatively less distinct. Our data provide the first evidence of enhanced coding of oddball sounds in a human auditory discrimination task and suggest the existence of an adaptive mechanism that tracks the long-term statistics of sounds and deploys coding resources accordingly.

"Change deafness" arising from inter-feature masking within a single auditory object.

Our ability to detect prominent changes in complex acoustic scenes depends not only on the ear's sensitivity but also on the capacity of the brain to process competing incoming information. Here, employing a combination of psychophysics and magnetoencephalography (MEG), we investigate listeners' sensitivity in situations when two features belonging to the same auditory object change in close succession. The auditory object under investigation is a sequence of tone pips characterized by a regularly repeating frequency pattern. Signals consisted of an initial, regularly alternating sequence of three short (60 msec) pure tone pips (in the form ABCABC…) followed by a long pure tone with a frequency that is either expected based on the on-going regular pattern ("LONG expected"-i.e., "LONG-expected") or constitutes a pattern violation ("LONG-unexpected"). The change in LONG-expected is manifest as a change in duration (when the long pure tone exceeds the established duration of a tone pip), whereas the change in LONG-unexpected is manifest as a change in both the frequency pattern and a change in the duration. Our results reveal a form of "change deafness," in that although changes in both the frequency pattern and the expected duration appear to be processed effectively by the auditory system-cortical signatures of both changes are evident in the MEG data-listeners often fail to detect changes in the frequency pattern when that change is closely followed by a change in duration. By systematically manipulating the properties of the changing features and measuring behavioral and MEG responses, we demonstrate that feature changes within the same auditory object, which occur close together in time, appear to compete for perceptual resources.