Conversational Interaction Is the Brain in Action: Implications for the Evaluation of Hearing and Hearing Interventions.

Humans have evolved the unique capacity to efficiently communicate using the spoken word. Hearing plays a key role as a receiver in this process and dysfunction leads to difficulties in listening and communication. It is widely accepted that effective communication is not adequately captured with current behavioral speech tests that principally focus on passive sound detection and speech recognition with idealized stimuli. To address the question of what it will take to obtain more ecologically valid outcomes from behavioral speech tests, recent approaches, and test paradigms devised to address some of the acknowledged shortcomings of current speech tests were reviewed. Additionally, some recent work which has focused on understanding brain function in social and dynamic interaction scenarios, so-called second person neuroscience, was reviewed. These reviews revealed that, while recent efforts in bridging the gap between behavioral speech tests and everyday communication situations represent important steps in the right direction, they are unlikely to provide a complete account of everyday communication situations. Further, brain imaging studies, together with our growing understanding of "mirror" neurons and the development of theories around embodied cognition, have demonstrated that the brain networks recruited during emotionally engaged interaction between interlocutors are far more complex when compared to that of a passive listener. Speech and nonspeech (e.g., gaze direction, body posture, etc.) interactions between the interlocutors give rise to the perception of effective interaction (sense of "agency") and activate neural networks important in decision-making and subsequent communication interaction. Successful conversational interaction represents the negotiation of a dynamic context and the emergence of a state of shared understanding between participants. In conclusion, to achieve highly ecologically valid outcomes related to communication, future testing will most likely require an interactive or conversational paradigm to elicit the brain states that are present in everyday social interactions.

The Quest for Ecological Validity in Hearing Science: What It Is, Why It Matters, and How to Advance It.

Ecological validity is a relatively new concept in hearing science. It has been cited as relevant with increasing frequency in publications over the past 20 years, but without any formal conceptual basis or clear motive. The sixth Eriksholm Workshop was convened to develop a deeper understanding of the concept for the purpose of applying it in hearing research in a consistent and productive manner. Inspired by relevant debate within the field of psychology, and taking into account the World Health Organization's International Classification of Functioning, Disability, and Health framework, the attendees at the workshop reached a consensus on the following definition: "In hearing science, ecological validity refers to the degree to which research findings reflect real-life hearing-related function, activity, or participation." Four broad purposes for striving for greater ecological validity in hearing research were determined: A (Understanding) better understanding the role of hearing in everyday life; B (Development) supporting the development of improved procedures and interventions; C (Assessment) facilitating improved methods for assessing and predicting ability to accomplish real-world tasks; and D (Integration and Individualization) enabling more integrated and individualized care. Discussions considered the effects of variables and phenomena commonly present in hearing-related research on the level of ecological validity of outcomes, supported by examples from a few selected outcome domains and for different types of studies. Illustrated with examples, potential strategies were offered for promoting a high level of ecological validity in a study and for how to evaluate the level of ecological validity of a study. Areas in particular that could benefit from more research to advance ecological validity in hearing science include: (1) understanding the processes of hearing and communication in everyday listening situations, and specifically the factors that make listening difficult in everyday situations; (2) developing new test paradigms that include more than one person (e.g., to encompass the interactive nature of everyday communication) and that are integrative of other factors that interact with hearing in real-life function; (3) integrating new and emerging technologies (e.g., virtual reality) with established test methods; and (4) identifying the key variables and phenomena affecting the level of ecological validity to develop verifiable ways to increase ecological validity and derive a set of benchmarks to strive for.

The monaural spectral cues identified by a reverse correlation analysis of free-field auditory localization data.

The outer-ear's location-dependent pattern of spectral filtering generates cues used to determine a sound source's elevation as well as front-back location. The authors aim to identify these features using a reverse correlation analysis (RCA), combining free-field localization behaviour with the associated head-related transfer functions' (HRTFs) magnitude spectrum from a sample of 73 participants. Localization responses were collected before and immediately after introducing a pair of outer-ear inserts which modified the listener's HRTFs to varying extent. The RCA identified several different features responsible for eliciting localization responses. The efficacy of these was examined using two models of monaural localization. In general, the predicted performance was closely aligned with the free-field localization error for the bare-ear condition; however, both models tended to grossly over-estimate the localization error based on HRTFs modified by the outer-ear inserts. The RCA's feature selection notably had the effect of better aligning the predicted performance of both models to the actual localization performance. This suggests that the RCA revealed sufficient detail for both models to correctly predict localization performance and also limited the influence of filtered-out elements in the distorted HRTFs that contributed to the degraded accuracy of both models.

Tracking the dynamic representation of consonants from auditory periphery to cortex.

In order to perceive meaningful speech, the auditory system must recognize different phonemes amidst a noisy and variable acoustic signal. To better understand the processing mechanisms underlying this ability, evoked cortical responses to different spoken consonants were measured with electroencephalography (EEG). Using multivariate pattern analysis (MVPA), binary classifiers attempted to discriminate between the EEG activity evoked by two given consonants at each peri-stimulus time sample, providing a dynamic measure of their cortical dissimilarity. To examine the relationship between representations at the auditory periphery and cortex, MVPA was also applied to modelled auditory-nerve (AN) responses of consonants, and time-evolving AN-based and EEG-based dissimilarities were compared with one another. Cortical dissimilarities between consonants were commensurate with their articulatory distinctions, particularly their manner of articulation, and to a lesser extent, their voicing. Furthermore, cortical distinctions between consonants in two periods of activity, centered at 130 and 400 ms after onset, aligned with their peripheral dissimilarities in distinct onset and post-onset periods, respectively. In relating speech representations across articulatory, peripheral, and cortical domains, the understanding of crucial transformations in the auditory pathway underlying the ability to perceive speech is advanced.

Characterisation of eppin function: expression and activity in the lung.

Eppin is a serine protease inhibitor expressed in male reproductive tissues.The aim of this study was to investigate the localisation and regulation of eppin expression in myeloid and epithelial cell lines, and explore its potential role as a multifunctional host defence protein.Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with acute respiratory distress syndrome and cystic fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with Toll-like receptor agonists, cytokines and hormone receptor agonists. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor. Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide-induced chemokine production. Furthermore, eppin inhibited lipopolysaccharide-induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In an in vivo model of lung inflammation induced by lipopolysaccharide, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine macrophage inflammatory protein-2.Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immune response in the lung.

Development and evaluation of a mixed gender, multi-talker matrix sentence test in Australian English.

OBJECTIVE: To develop, in Australian English, the first mixed-gender, multi-talker matrix sentence test. DESIGN: Speech material consisted of a 50-word base matrix whose elements can be combined to form sentences of identical syntax but unpredictable content. Ten voices (five female and five male) were recorded for editing and preliminary level equalization. Elements were presented as single-talker sentences-in-noise during two perceptual tests: an optimization phase that provided the basis for further level correction, and an evaluation phase that perceptually validated those changes. STUDY SAMPLE: Ten listeners participated in the optimization phase; these and an additional 32 naïve listeners completed the evaluation test. All were fluent in English and all but one had lived in Australia for >2 years. RESULTS: Optimization reduced the standard deviation (SD) and speech reception threshold (SRT) range across all speech material (grand mean SRT = -10.6 dB signal-to-noise ratio, median = -10.8, SD =1.4, range =13.7, slope =19.3%/dB), yielding data consistent with cross-validated matrix tests in other languages. Intelligibility differences between experienced and naïve listeners were minimal. CONCLUSIONS: The Australian matrix corpus provides a robust set of test materials suitable for both clinical assessment and research into the dynamics of active listening in multi-talker environments.

Accommodating to new ears: the effects of sensory and sensory-motor feedback.

Changing the shape of the outer ear using small in-ear molds degrades sound localization performance consistent with the distortion of monaural spectral cues to location. It has been shown recently that adult listeners re-calibrate to these new spectral cues for locations both inside and outside the visual field. This raises the question as to the teacher signal for this remarkable functional plasticity. Furthermore, large individual differences in the extent and rate of accommodation suggests a number of factors may be driving this process. A training paradigm exploiting multi-modal and sensory-motor feedback during accommodation was examined to determine whether it might accelerate this process. So as to standardize the modification of the spectral cues, molds filling 40% of the volume of each outer ear were custom made for each subject. Daily training sessions for about an hour, involving repetitive auditory stimuli and exploratory behavior by the subject, significantly improved the extent of accommodation measured by both front-back confusions and polar angle localization errors, with some improvement in the rate of accommodation demonstrated by front-back confusion errors. This work has implications for both the process by which a coherent representation of auditory space is maintained and for accommodative training for hearing aid wearers.

The effect of velocity on auditory representational momentum.

"Representational Momentum" (RM) is a mislocalization of the endpoint of a moving target in the direction of motion. In vision, RM has been shown to increase with target velocity. In audition, however, the effect of target velocity is unclear. Using a perceptual paradigm with moving broadband noise targets in Virtual Auditory Space resulted in a linear increase in RM from 0.9° to 2.3° for an increase in target velocity from 25°/s to 100°/s. Accounting for the effect of eye position also reduced variance. These results suggest that RM may be the result of similar underlying mechanisms in both modalities.

Acoustic analysis of the directional information captured by five different hearing aid styles.

This study compared the head-related transfer functions (HRTFs) recorded from the bare ear of a mannequin for 393 spatial locations and for five different hearing aid styles: Invisible-in-the-canal (IIC), completely-in-the-canal (CIC), in-the-canal (ITC), in-the-ear (ITE), and behind-the-ear (BTE). The spectral distortions of each style compared to the bare ear were described qualitatively in terms of the gain and frequency characteristics of the prominent spectral notch and two peaks in the HRTFs. Two quantitative measures of the differences between the HRTF sets and a measure of the dissimilarity of the HRTFs within each set were also computed. In general, the IIC style was most similar and the BTE most dissimilar to the bare ear recordings. The relative similarities among the CIC, ITC, and ITE styles depended on the metric employed. The within-style spectral dissimilarities were comparable for the bare ear, IIC, CIC, and ITC with increasing ambiguity for the ITE and BTE styles. When the analysis bandwidth was limited to 8 kHz, the HRTFs within each set became much more similar.

Type 1 interferons promote Staphylococcus aureus nasal colonization by inducing phagocyte apoptosis.

Staphylococcus aureus is an important human commensal which persistently colonizes up to 30% of the human population, predominantly within the nasal cavity. The commensal lifestyle of S. aureus is complex, and the mechanisms underpinning colonization are not fully understood. S. aureus can induce an immunosuppressive environment in the nasal tissue (NT) by driving IL-10 and IL-27 to facilitate nasal colonization, indicating that S. aureus has the capacity to modulate the local immune environment for its commensal habitation. Mounting evidence suggests commensal bacteria drive type 1 interferons (IFN-I) to establish an immunosuppressive environment and whilst S. aureus can induce IFN-I during infection, its role in colonization has not yet been examined. Here, we show that S. aureus preferentially induces IFN signaling in macrophages. This IFN-I in turn upregulates expression of proapoptotic genes within macrophages culminating in caspase-3 cleavage. Importantly, S. aureus was found to drive phagocytic cell apoptosis in the nasal tissue during nasal colonization in an IFN-I dependent manner with colonization significantly reduced under caspase-3 inhibition. Overall, loss of IFN-I signaling significantly diminished S. aureus nasal colonization implicating a pivotal role for IFN-I in controlling S. aureus persistence during colonization through its ability to induce phagocyte apoptosis. Together, this study reveals a novel strategy utilized by S. aureus to circumvent host immunity in the nasal mucosa to facilitate nasal colonization.

IL-10 inhibition during immunization improves vaccine-induced protection against Staphylococcus aureus infection.

Staphylococcus aureus is a major human pathogen. An effective anti-S. aureus vaccine remains elusive as the correlates of protection are ill-defined. Targeting specific T cell populations is an important strategy for improving anti-S. aureus vaccine efficacy. Potential bottlenecks that remain are S. aureus-induced immunosuppression and the impact this might have on vaccine-induced immunity. S. aureus induces IL-10, which impedes effector T cell responses, facilitating persistence during both colonization and infection. Thus, it was hypothesized that transient targeting of IL-10 might represent an innovative way to improve vaccine efficacy. In this study, IL-10 expression was elevated in the nares of persistent carriers of S. aureus, and this was associated with reduced systemic S. aureus-specific Th1 responses. This suggests that systemic responses are remodeled because of commensal exposure to S. aureus, which negatively implicates vaccine function. To provide proof of concept that targeting immunosuppressive responses during immunization may be a useful approach to improve vaccine efficacy, we immunized mice with T cell-activating vaccines in combination with IL-10-neutralizing antibodies. Blocking IL-10 during vaccination enhanced effector T cell responses and improved bacterial clearance during subsequent systemic and subcutaneous infection. Taken together, these results reveal a potentially novel strategy for improving anti-S. aureus vaccine efficacy.

PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection.

PYHIN proteins AIM2 and IFI204 sense pathogen DNA, while other PYHINs have been shown to regulate host gene expression through as-yet unclear mechanisms. We characterize mouse PYHIN IFI207, which we find is not involved in DNA sensing but rather is required for cytokine promoter induction in macrophages. IFI207 co-localizes with both active RNA polymerase II (RNA Pol II) and IRF7 in the nucleus and enhances IRF7-dependent gene promoter induction. Generation of Ifi207-/- mice shows no role for IFI207 in autoimmunity. Rather, IFI207 is required for the establishment of a Klebsiella pneumoniae lung infection and for Klebsiella macrophage phagocytosis. These insights into IFI207 function illustrate that PYHINs can have distinct roles in innate immunity independent of DNA sensing and highlight the need to better characterize the whole mouse locus, one gene at a time.

Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae.

Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3-4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICESp23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICESp23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role.

Compression of auditory space during rapid head turns.

Studies of spatial perception during visual saccades have demonstrated compressions of visual space around the saccade target. Here we psychophysically investigated perception of auditory space during rapid head turns, focusing on the "perisaccadic" interval. Using separate perceptual and behavioral response measures we show that spatial compression also occurs for rapid head movements, with the auditory spatial representation compressing by up to 50%. Similar to observations in the visual system, this occurred only when spatial locations were measured by using a perceptual response; it was absent for the behavioral measure involving a nose-pointing task. These findings parallel those observed in vision during saccades and suggest that a common neural mechanism may subserve these distortions of space in each modality.

Masker location uncertainty reveals evidence for suppression of maskers in two-talker contexts.

In many natural settings, spatial release from masking aids speech intelligibility, especially when there are competing talkers. This paper describes a series of three experiments that investigate the role of prior knowledge of masker location on phoneme identification and spatial release from masking. In contrast to previous work, these experiments use initial stop-consonant identification as a test of target intelligibility to ensure that listeners had little time to switch the focus of spatial attention during the task. The first experiment shows that target phoneme identification was worse when a masker played from an unexpected location (increasing the consonant identification threshold by 2.6 dB) compared to when an energetically very similar and symmetrically located masker came from an expected location. In the second and third experiments, target phoneme identification was worse (increasing target threshold levels by 2.0 and 2.6 dB, respectively) when the target was played unexpectedly on the side from which the masker was expected compared to when the target came from an unexpected, symmetrical location in the hemifield opposite the expected location of the masker. These results support the idea that listeners modulate spatial attention by both focusing resources on the expected target location and withdrawing attentional resources from expected locations of interfering sources.

Localization in speech mixtures by listeners with hearing loss.

The ability of listeners with bilateral sensorineural hearing loss to localize a speech source in a multitalker mixture was measured. Five simultaneous words spoken by different talkers were presented over loudspeakers in a small room, and listeners localized one target word. Errors were significantly larger in this group compared to a control group with normal hearing. Localization of the target presented alone was not different between groups. The results suggest that hearing loss does not impair spatial hearing per se, but degrades the spatial representation of multiple simultaneous sounds.

The Impact of Lung Proteases on Snake-Derived Antimicrobial Peptides.

Respiratory infections are a leading cause of global morbidity and mortality and are of significant concern for individuals with chronic inflammatory lung diseases. There is an urgent need for novel antimicrobials. Antimicrobial peptides (AMPs) are naturally occurring innate immune response peptides with therapeutic potential. However, therapeutic development has been hindered by issues with stability and cytotoxicity. Availing of direct drug delivery to the affected site, for example the lung, can reduce unwanted systemic side effects and lower the required dose. As cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) lungs typically exhibit elevated protease levels, the aim of this study was to assess their impact on snake-derived AMPs. Peptide cleavage was determined using SDS-PAGE and antimicrobial and anti-inflammatory activities of neutrophil elastase (NE)-incubated peptides were assessed using a radial diffusion assay (RDA) and an in vitro LPS-induced inflammation model, respectively. Although the snake-derived AMPs were found to be susceptible to cleavage by lung proteases including NE, several retained their function following NE-incubation. This facilitated the design of novel truncated derivatives that retained functionality following NE incubation. Snake-derived AMPs are tractable candidate treatments for use in environments that feature elevated NE levels, such as the CF airways.

Speech localization in a multitalker mixture.

An experiment was performed that measured, for the frontal audio-visual horizon, how accurately listeners could localize a female-voice target amidst four spatially distributed male-voice maskers. To examine whether listeners can make use of a priori knowledge about the configuration of the sources, performance was examined in two conditions: either the masker locations were fixed (in one of five known patterns) or the locations varied from trial to trial. The presence of maskers disrupted speech localization, even after accounting for reduced target detectability. Averaged across all target locations, the rms error in responses decreased by 20% when a priori knowledge about masker locations was available. The effect was even stronger for the target locations that did not coincide with the maskers (error reduction of 36%), while no change in errors was observed for targets coinciding with maskers. The benefits were reduced when the target-to-masker intensity ratio was increased or when the maskers were in a pattern that made it difficult to make use of the a priori information. The results confirm that localization in speech mixtures is modified by the listener's expectations about the spatial arrangement of the sources.

Phase effects on the perceived elevation of complex tones.

Free-field source localization experiments with 30 source locations, symmetrically distributed in azimuth, elevation, and front-back location, were performed with periodic tones having different phase relationships among their components. Although the amplitude spectra were the same for these different kinds of stimuli, the tones with certain phase relationships were successfully localized while the tones with other phases led to large elevation errors and front-back reversals, normally growing with stimulus level. The results show that it is not enough to have a smooth, broadband, long-term signal spectrum for successful sagittal-plane localization. Instead, temporal factors are important. A model calculation investigates the idea that the tonotopic details that mediate localization need to be simultaneously, or almost simultaneously, accessible in the auditory system in order to achieve normal elevation perception. A qualitative model based on lateral inhibition seems capable in principle of accounting for both the phase effects and level effects.