Hidden hearing loss: Fifteen years at a glance.

Hearing loss affects approximately 18% of the population worldwide. Hearing difficulties in noisy environments without accompanying audiometric threshold shifts likely affect an even larger percentage of the global population. One of the potential causes of hidden hearing loss is cochlear synaptopathy, the loss of synapses between inner hair cells (IHC) and auditory nerve fibers (ANF). These synapses are the most vulnerable structures in the cochlea to noise exposure or aging. The loss of synapses causes auditory deafferentation, i.e., the loss of auditory afferent information, whose downstream effect is the loss of information that is sent to higher-order auditory processing stages. Understanding the physiological and perceptual effects of this early auditory deafferentation might inform interventions to prevent later, more severe hearing loss. In the past decade, a large body of work has been devoted to better understand hidden hearing loss, including the causes of hidden hearing loss, their corresponding impact on the auditory pathway, and the use of auditory physiological measures for clinical diagnosis of auditory deafferentation. This review synthesizes the findings from studies in humans and animals to answer some of the key questions in the field, and it points to gaps in knowledge that warrant more investigation. Specifically, recent studies suggest that some electrophysiological measures have the potential to function as indicators of hidden hearing loss in humans, but more research is needed for these measures to be included as part of a clinical test battery.

Quantifying the Impact of Auditory Deafferentation on Speech Perception.

The past decade has seen a wealth of research dedicated to determining which and how morphological changes in the auditory periphery contribute to people experiencing hearing difficulties in noise despite having clinically normal audiometric thresholds in quiet. Evidence from animal studies suggests that cochlear synaptopathy in the inner ear might lead to auditory nerve deafferentation, resulting in impoverished signal transmission to the brain. Here, we quantify the likely perceptual consequences of auditory deafferentation in humans via a physiologically inspired encoding-decoding model. The encoding stage simulates the processing of an acoustic input stimulus (e.g., speech) at the auditory periphery, while the decoding stage is trained to optimally regenerate the input stimulus from the simulated auditory nerve firing data. This allowed us to quantify the effect of different degrees of auditory deafferentation by measuring the extent to which the decoded signal supported the identification of speech in quiet and in noise. In a series of experiments, speech perception thresholds in quiet and in noise increased (worsened) significantly as a function of the degree of auditory deafferentation for modeled deafferentation greater than 90%. Importantly, this effect was significantly stronger in a noisy than in a quiet background. The encoding-decoding model thus captured the hallmark symptom of degraded speech perception in noise together with normal speech perception in quiet. As such, the model might function as a quantitative guide to evaluating the degree of auditory deafferentation in human listeners.

MEG correlates of temporal regularity relevant to pitch perception in human auditory cortex.

We recorded neural responses in human participants to three types of pitch-evoking regular stimuli at rates below and above the lower limit of pitch using magnetoencephalography (MEG). These bandpass filtered (1-4 kHz) stimuli were harmonic complex tones (HC), click trains (CT), and regular interval noise (RIN). Trials consisted of noise-regular-noise (NRN) or regular-noise-regular (RNR) segments in which the repetition rate (or fundamental frequency F0) was either above (250 Hz) or below (20 Hz) the lower limit of pitch. Neural activation was estimated and compared at the senor and source levels. The pitch-relevant regular stimuli (F0 = 250 Hz) were all associated with marked evoked responses at around 140 ms after noise-to-regular transitions at both sensor and source levels. In particular, greater evoked responses to pitch-relevant stimuli than pitch-irrelevant stimuli (F0 = 20 Hz) were localized along the Heschl's sulcus around 140 ms. The regularity-onset responses for RIN were much weaker than for the other types of regular stimuli (HC, CT). This effect was localized over planum temporale, planum polare, and lateral Heschl's gyrus. Importantly, the effect of pitch did not interact with the stimulus type. That is, we did not find evidence to support different responses for different types of regular stimuli from the spatiotemporal cluster of the pitch effect (∼140 ms). The current data demonstrate cortical sensitivity to temporal regularity relevant to pitch that is consistently present across different pitch-relevant stimuli in the Heschl's sulcus between Heschl's gyrus and planum temporale, both of which have been identified as a "pitch center" based on different modalities.

Dynamics underlying auditory-object-boundary detection in primary auditory cortex.

Auditory object analysis requires the fundamental perceptual process of detecting boundaries between auditory objects. However, the dynamics underlying the identification of discontinuities at object boundaries are not well understood. Here, we employed a synthetic stimulus composed of frequency-modulated ramps known as 'acoustic textures', where boundaries were created by changing the underlying spectrotemporal statistics. We collected magnetoencephalographic (MEG) data from human volunteers and observed a slow (<1 Hz) post-boundary drift in the neuromagnetic signal. The response evoking this drift signal was source localised close to Heschl's gyrus (HG) bilaterally, which is in agreement with a previous functional magnetic resonance imaging (fMRI) study that found HG to be involved in the detection of similar auditory object boundaries. Time-frequency analysis demonstrated suppression in alpha and beta bands that occurred after the drift signal.

An Analytical Framework of Tonal and Rhythmic Hierarchy in Natural Music Using the Multivariate Temporal Response Function.

Even without formal training, humans experience a wide range of emotions in response to changes in musical features, such as tonality and rhythm, during music listening. While many studies have investigated how isolated elements of tonal and rhythmic properties are processed in the human brain, it remains unclear whether these findings with such controlled stimuli are generalizable to complex stimuli in the real world. In the current study, we present an analytical framework of a linearized encoding analysis based on a set of music information retrieval features to investigate the rapid cortical encoding of tonal and rhythmic hierarchies in natural music. We applied this framework to a public domain EEG dataset (OpenMIIR) to deconvolve overlapping EEG responses to various musical features in continuous music. In particular, the proposed framework investigated the EEG encoding of the following features: tonal stability, key clarity, beat, and meter. This analysis revealed a differential spatiotemporal neural encoding of beat and meter, but not of tonal stability and key clarity. The results demonstrate that this framework can uncover associations of ongoing brain activity with relevant musical features, which could be further extended to other relevant measures such as time-resolved emotional responses in future studies.

An Objective Approach Toward Understanding Auditory Processing Disorder.

Purpose In the field of audiology, auditory processing disorder (APD) continues to be a topic of ongoing debate for clinicians and scientists alike, both in terms of theory and clinical practice. In the current viewpoint, we first lay out the main issues that are central to the controversy surrounding APD, and then suggest a framework toward their resolution. Method The current viewpoint is informed by reviewing existing studies in the field of APD to better understand the issues contributing to the controversies in APD. Results We found that, within the current definition of APD, the two main issues that make the APD diagnosis controversial are (a) comorbidity with other disorders and (b) the lack of domain specificity. These issues remain unresolved, especially with the use of the existing behavioral APD test batteries. In this viewpoint, we shed light on how they can be mitigated by implementing the administration of an objective, physiological test battery. Conclusions By administering an objective test battery, as proposed in this viewpoint, we believe that it will be possible to achieve a higher degree of specificity to the auditory domain that will not only contribute towards clinical practice but also contribute towards strengthening APD as a theoretical construct.

From acoustic to linguistic analysis of temporal speech structure: Acousto-linguistic transformation during speech perception using speech quilts.

Speech perception entails the mapping of the acoustic waveform to linguistic representations. For this transformation to succeed, the speech signal needs to be tracked over various temporal windows at high temporal precision in order to decode linguistic units ranging from phonemes (tens of milliseconds) to sentences (seconds). Here, we tested the hypothesis that cortical processing of speech-specific temporal structure is modulated by higher-level linguistic analysis. Using fMRI, we measured BOLD signal changes to 4 s long speech quilts with variable temporal structure (30, 120, 480, 960 ms segment lengths), as well as natural speech, created from a familiar (English) or foreign (Korean) language. We found evidence for the acoustic analysis of temporal speech properties in superior temporal sulcus (STS): the BOLD signal increased as a function of temporal speech structure in both familiar and foreign languages. However, activity in left inferior gyrus (IFG) revealed evidence for linguistic processing of temporal speech properties: the BOLD signal increased as a function of temporal speech structure only in familiar, but not in foreign speech. Network connectivity analyses suggested that left IFG modulates the processing of temporal speech structure in primary and non-primary auditory cortex, which in turn sensitizes the analysis of temporal speech structure in STS. The results thus suggest that acousto-linguistic transformation of temporal speech structure is achieved by a cortical network comprising primary and non-primary auditory cortex, STS, and left IFG.

Modulation change detection in human auditory cortex: Evidence for asymmetric, non-linear edge detection.

Changes in modulation rate are important cues for parsing acoustic signals, such as speech. We parametrically controlled modulation rate via the correlation coefficient (r) of amplitude spectra across fixed frequency channels between adjacent time frames: broadband modulation spectra are biased toward slow modulate rates with increasing r, and vice versa. By concatenating segments with different r, acoustic changes of various directions (e.g., changes from low to high correlation coefficients, that is, random-to-correlated or vice versa) and sizes (e.g., changes from low to high or from medium to high correlation coefficients) can be obtained. Participants listened to sound blocks and detected changes in correlation while MEG was recorded. Evoked responses to changes in correlation demonstrated (a) an asymmetric representation of change direction: random-to-correlated changes produced a prominent evoked field around 180 ms, while correlated-to-random changes evoked an earlier response with peaks at around 70 and 120 ms, whose topographies resemble those of the canonical P50m and N100m responses, respectively, and (b) a highly non-linear representation of correlation structure, whereby even small changes involving segments with a high correlation coefficient were much more salient than relatively large changes that did not involve segments with high correlation coefficients. Induced responses revealed phase tracking in the delta and theta frequency bands for the high correlation stimuli. The results confirm a high sensitivity for low modulation rates in human auditory cortex, both in terms of their representation and their segregation from other modulation rates.

The distribution and nature of responses to broadband sounds associated with pitch in the macaque auditory cortex.

The organisation of pitch-perception mechanisms in the primate cortex is controversial, in that divergent results have been obtained, ranging from a single circumscribed 'pitch centre' to systems widely distributed across auditory cortex. Possible reasons for such discrepancies include different species, recording techniques, pitch stimuli, sampling of auditory fields, and the neural metrics recorded. In the present study, we sought to bridge some of these divisions by examining activity related to pitch in both neurons and neuronal ensembles within the auditory cortex of the rhesus macaque, a primate species with similar pitch perception and auditory cortical organisation to humans. We demonstrate similar responses, in primary and non-primary auditory cortex, to two different types of broadband pitch above the macaque lower limit in both neurons and local field potential (LFP) gamma oscillations. The majority of broadband pitch responses in neurons and LFP sites did not show equivalent tuning for sine tones.

The cortical analysis of speech-specific temporal structure revealed by responses to sound quilts.

Speech contains temporal structure that the brain must analyze to enable linguistic processing. To investigate the neural basis of this analysis, we used sound quilts, stimuli constructed by shuffling segments of a natural sound, approximately preserving its properties on short timescales while disrupting them on longer scales. We generated quilts from foreign speech to eliminate language cues and manipulated the extent of natural acoustic structure by varying the segment length. Using functional magnetic resonance imaging, we identified bilateral regions of the superior temporal sulcus (STS) whose responses varied with segment length. This effect was absent in primary auditory cortex and did not occur for quilts made from other natural sounds or acoustically matched synthetic sounds, suggesting tuning to speech-specific spectrotemporal structure. When examined parametrically, the STS response increased with segment length up to ∼500 ms. Our results identify a locus of speech analysis in human auditory cortex that is distinct from lexical, semantic or syntactic processes.

Sensitivity to temporal modulation rate and spectral bandwidth in the human auditory system: fMRI evidence.

Hierarchical models of auditory processing often posit that optimal stimuli, i.e., those eliciting a maximal neural response, will increase in bandwidth and decrease in modulation rate as one ascends the auditory neuraxis. Here, we tested how bandwidth and modulation rate interact at several loci along the human central auditory pathway using functional MRI in a cardiac-gated, sparse acquisition design. Participants listened passively to both narrowband (NB) and broadband (BB) carriers (1/4- or 4-octave pink noise), which were jittered about a mean sinusoidal amplitude modulation rate of 0, 3, 29, or 57 Hz. The jittering was introduced to minimize stimulus-specific adaptation. The results revealed a clear difference between spectral bandwidth and temporal modulation rate: sensitivity to bandwidth (BB > NB) decreased from subcortical structures to nonprimary auditory cortex, whereas sensitivity to slow modulation rates was largest in nonprimary auditory cortex and largely absent in subcortical structures. Furthermore, there was no parametric interaction between bandwidth and modulation rate. These results challenge simple hierarchical models, in that BB stimuli evoked stronger responses in primary auditory cortex (and subcortical structures) rather than nonprimary cortex. Furthermore, the strong preference for slow modulation rates in nonprimary cortex demonstrates the compelling global sensitivity of auditory cortex to modulation rates that are dominant in the principal signals that we process, e.g., speech.

Gamma band pitch responses in human auditory cortex measured with magnetoencephalography.

We have previously used direct electrode recordings in two human subjects to identify neural correlates of the perception of pitch (Griffiths, Kumar, Sedley et al., Direct recordings of pitch responses from human auditory cortex, Curr. Biol. 22 (2010), pp. 1128-1132). The present study was carried out to assess virtual-electrode measures of pitch perception based on non-invasive magnetoencephalography (MEG). We recorded pitch responses in 13 healthy volunteers using a passive listening paradigm and the same pitch-evoking stimuli (regular interval noise; RIN) as in the previous study. Source activity was reconstructed using a beamformer approach, which was used to place virtual electrodes in auditory cortex. Time-frequency decomposition of these data revealed oscillatory responses to pitch in the gamma frequency band to occur, in Heschl's gyrus, from 60 Hz upwards. Direct comparison of these pitch responses to the previous depth electrode recordings shows a striking congruence in terms of spectrotemporal profile and anatomical distribution. These findings provide further support that auditory high gamma oscillations occur in association with RIN pitch stimuli, and validate the use of MEG to assess neural correlates of normal and abnormal pitch perception.

Cortical mechanisms for the segregation and representation of acoustic textures.

Auditory object analysis requires two fundamental perceptual processes: the definition of the boundaries between objects, and the abstraction and maintenance of an object's characteristic features. Although it is intuitive to assume that the detection of the discontinuities at an object's boundaries precedes the subsequent precise representation of the object, the specific underlying cortical mechanisms for segregating and representing auditory objects within the auditory scene are unknown. We investigated the cortical bases of these two processes for one type of auditory object, an "acoustic texture," composed of multiple frequency-modulated ramps. In these stimuli, we independently manipulated the statistical rules governing (1) the frequency-time space within individual textures (comprising ramps with a given spectrotemporal coherence) and (2) the boundaries between textures (adjacent textures with different spectrotemporal coherences). Using functional magnetic resonance imaging, we show mechanisms defining boundaries between textures with different coherences in primary and association auditory cortices, whereas texture coherence is represented only in association cortex. Furthermore, participants' superior detection of boundaries across which texture coherence increased (as opposed to decreased) was reflected in a greater neural response in auditory association cortex at these boundaries. The results suggest a hierarchical mechanism for processing acoustic textures that is relevant to auditory object analysis: boundaries between objects are first detected as a change in statistical rules over frequency-time space, before a representation that corresponds to the characteristics of the perceived object is formed.

Encoding of spectral correlation over time in auditory cortex.

Natural sounds contain multiple spectral components that vary over time. The degree of variation can be characterized in terms of correlation between successive time frames of the spectrum, or as a time window within which any two frames show a minimum degree of correlation: the greater the correlation of the spectrum between successive time frames, the longer the time window. Recent studies suggest differences in the encoding of shorter and longer time windows in left and right auditory cortex, respectively. The present functional magnetic resonance imaging study assessed brain activation in response to the systematic variation of the time window in complex spectra that are more similar to natural sounds than in previous studies. The data show bilateral activity in the planum temporale and anterior superior temporal gyrus as a function of increasing time windows, as well as activity in the superior temporal sulcus that was significantly lateralized to the right. The results suggest a coexistence of hierarchical and lateralization schemes for representing increasing time windows in auditory association cortex.

fMRI evidence for a cortical hierarchy of pitch pattern processing.

Pitch patterns, such as melodies, consist of two levels of structure: a global level, comprising the pattern of ups and downs, or contour; and a local level, comprising the precise intervals that make up this contour. An influential neuropsychological model suggests that these two levels of processing are hierarchically linked, with processing of the global structure occurring within the right hemisphere in advance of local processing within the left. However, the predictions of this model and its anatomical basis have not been tested in neurologically normal individuals. The present study used fMRI and required participants to listen to consecutive pitch sequences while performing a same/different one-back task. Sequences, when different, either preserved (local) or violated (global) the contour of the sequence preceding them. When the activations for the local and global conditions were contrasted directly, additional activation was seen for local processing in right planum temporale and posterior superior temporal sulcus (pSTS). The presence of additional activation for local over global processing supports the hierarchical view that the global structure of a pitch sequence acts as a "framework" on which the local detail is subsequently hung. However, the lateralisation of activation seen in the present study, with global processing occurring in left pSTS and local processing occurring bilaterally, differed from that predicted by the neuroanatomical model. A re-examination of the individual lesion data on which the neuroanatomical model is based revealed that the lesion data equally well support the laterality scheme suggested by our data. While the present study supports the hierarchical view of local and global processing, there is an evident need for further research, both in patients and neurologically normal individuals, before an understanding of the functional lateralisation of local and global processing can be considered established.

An information theoretic characterisation of auditory encoding.

The entropy metric derived from information theory provides a means to quantify the amount of information transmitted in acoustic streams like speech or music. By systematically varying the entropy of pitch sequences, we sought brain areas where neural activity and energetic demands increase as a function of entropy. Such a relationship is predicted to occur in an efficient encoding mechanism that uses less computational resource when less information is present in the signal: we specifically tested the hypothesis that such a relationship is present in the planum temporale (PT). In two convergent functional MRI studies, we demonstrated this relationship in PT for encoding, while furthermore showing that a distributed fronto-parietal network for retrieval of acoustic information is independent of entropy. The results establish PT as an efficient neural engine that demands less computational resource to encode redundant signals than those with high information content.