Auditory Research publications

This study explored the extent to which informational masking of speech depends on the frequency region and number of extraneous formants in an interferer. Target formants—monotonized three-formant (F1+F2+F3) analogues of natural sentences—were presented monaurally, with target ear assigned randomly on each trial. Interferers were presented contralaterally. In experiment 1, single-formant interferers were created using the time-reversed F2 frequency contour and constant amplitude, root-mean-square (RMS)-matched to F2. Interferer center frequency was matched to that of F1, F2, or F3, while maintaining the extent of formant-frequency variation (depth) on a log scale. Adding an interferer lowered intelligibility; the effect of frequency region was small and broadly tuned around F2. In experiment 2, interferers comprised either one formant (F1, the most intense) or all three, created using the time-reversed frequency contours of the corresponding targets and RMS-matched constant amplitudes. Interferer formant-frequency variation was scaled to 0%, 50%, or 100% of the original depth. Increasing the depth of formant-frequency variation and number of formants in the interferer had independent and additive effects. These findings suggest that the impact on intelligibility depends primarily on the overall extent of frequency variation in each interfering formant (up to ∼100% depth) and the number of extraneous formants.

Mutations in the GJB2 gene [which encodes connexin 26 (Cx26)] are the most common causes of hereditary hearing loss in humans, and previous studies showed postnatal development arrest of the organ of Corti in different Cx26-null mouse models. To explore the pathological changes and the mechanism behind the cochlear abnormalities in these mice further, we established transgenic mouse models by conditional knockdown of cochlear Cx26 at postnatal day (P) 0 and P8. Auditory brainstem responses were recorded and the morphological features in the organ of Corti were analyzed 18 days after Cx26 knockdown. Mice in the P0 knockdown group displayed severe hearing loss at all frequencies, whereas mice in the P8 knockdown group showed nearly normal hearing. In the P8 knockdown group, the organ of Corti displayed normal architecture, and no ultrastructural changes were observed. In the P0 knockdown group, the phalangeal processes of Deiter's cells did not develop into finger-like structures, and the formation of microtubules in the pillar cells was significantly reduced; moreover, the amount of acetylated α-tubulin was reduced in pillar cells. Our results indicate that Gjb2 participates in postnatal development of the cytoskeleton in pillar cells during structural maturation of the organ of Corti. In P0 knockdown mice, the reduction in microtubules in pillar cells might be responsible for the failure of the tunnel of Corti to open, and the malformed phalangeal processes might negatively affect the supporting framework of the organ of Corti, which would be a new mechanism of Gjb2-related hearing loss.

The ability to identify who is talking is an important aspect of communication in social situations and, while empirical data are limited, it is possible that a disruption to this ability contributes to the difficulties experienced by listeners with hearing loss. In this study, talker identification was examined under both quiet and masked conditions. Subjects were grouped by hearing status (normal hearing/sensorineural hearing loss) and age (younger/older adults). Listeners first learned to identify the voices of four same-sex talkers in quiet, and then talker identification was assessed (1) in quiet, (2) in speech-shaped, steady-state noise, and (3) in the presence of a single, unfamiliar same-sex talker. Both younger and older adults with hearing loss, as well as older adults with normal hearing, generally performed more poorly than younger adults with normal hearing, although large individual differences were observed in all conditions. Regression analyses indicated that both age and hearing loss were predictors of performance in quiet, and there was some evidence for an additional contribution of hearing loss in the presence of masking. These findings suggest that both hearing loss and age may affect the ability to identify talkers in “cocktail party” situations.

Sound onsets dominate spatial judgments of many types of periodic sound. Conversely, ongoing cues often dominate in spatial judgments of aperiodic noise. This study quantified onset dominance as a function of both the bandwidth and the temporal regularity of stimuli by measuring temporal weighting functions (TWF) from Stecker, Ostreicher, and Brown [(2013) J. Acoust. Soc. Am. 134, 1242–1252] for lateralization of periodic and aperiodic noise-burst trains. Stimuli consisted of 16 noise bursts (1 ms each) repeating at an interval of 2 or 5 ms. TWFs were calculated by multiple regression of lateralization judgments onto interaural time and level differences, which varied independently (±100 μs, ±2 dB) across bursts. Noise tokens were either refreshed on each burst (aperiodic) or repeated across sets of 2, 4, 8, or 16 bursts. TWFs revealed strong onset dominance for periodic noise-burst trains (16 repeats per token), which was markedly reduced in aperiodic trains. A second experiment measured TWFs for periodic but sinusoidally amplitude-modulated noise burst trains, revealing greater weight on the earliest and least intense bursts of the rising envelope slope. The results support the view that envelope fluctuations drive access to binaural information in both periodic and aperiodic sounds.

There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.

The prolonged masking of auditory inputs with white noise has been shown to reopen the critical period for spectral tuning in the adult rat auditory cortex. Here, we argue that the masking of salient temporal inputs in particular is responsible for changes in neuronal activity that lead to this experience-dependent plasticity. We tested this hypothesis by passively exposing adult rats to 2 weeks of amplitude-modulated (AM) white noise with different modulation depths from 0% (no modulation) to 100% (strong modulation). All exposed rats displayed evidence of cortical plasticity as measured by receptive field bandwidths, tonotopic gradients, and synchronization during spontaneous activity. However, this plasticity was fundamentally different in nature for rats exposed to unmodulated noise, as a second passive exposure to pure tones elicited tonotopic reorganization in rats exposed to 0% AM noise only. Detection of c-FOS expression in excitatory and inhibitory cells through post-mortem immunohistochemistry also revealed different patterns of cellular activation depending on modulation depth. Together, these results indicate that the absence of temporal modulation promotes noise-induced plasticity in the adult auditory cortex and suggest an important and continuous role for temporally salient inputs in the maintenance of mature auditory circuits.

Extracellular recording studies have revealed diverse and selective neural responses in the primary auditory cortex (A1) of awake animals. However, we have limited knowledge on subthreshold events that give rise to these responses, especially in non-human primates, as intracellular recordings in awake animals pose substantial technical challenges. We developed a novel intracellular recording technique in awake marmosets to systematically study subthreshold activity of A1 neurons that underlies their diverse and selective spiking responses. Our findings showed that in contrast to predominantly transient depolarization observed in A1 of anesthetized animals, both transient and sustained depolarization (during or beyond the stimulus period) were observed. Comparing with spiking responses, subthreshold responses were often longer lasting in duration and more broadly tuned in frequency, and showed narrower intensity tuning in non-monotonic neurons and lower response threshold in monotonic neurons. These observations demonstrated the enhancement of stimulus selectivity from subthreshold to spiking responses in individual A1 neurons. Furthermore, A1 neurons classified as regular- or fast-spiking subpopulation based on their spike shapes exhibited distinct response properties in frequency and intensity domains. These findings provide valuable insights into cortical integration and transformation of auditory information at the cellular level in auditory cortex of awake non-human primates.

Excitatory and inhibitory neurons in the mammalian sensory cortex form interconnected circuits that control cortical stimulus selectivity and sensory acuity. Theoretical studies have predicted that suppression of inhibition in such excitatory–inhibitory networks can lead to either an increase or, paradoxically, a decrease in excitatory neuronal firing, with consequent effects on stimulus selectivity. We tested whether modulation of inhibition or excitation in the auditory cortex of male mice could evoke such a variety of effects in tone-evoked responses and in behavioral frequency discrimination acuity. We found that, indeed, the effects of optogenetic manipulation on stimulus selectivity and behavior varied in both magnitude and sign across subjects, possibly reflecting differences in circuitry or expression of optogenetic factors. Changes in neural population responses consistently predicted behavioral changes for individuals separately, including improvement and impairment in acuity. This correlation between cortical and behavioral change demonstrates that, despite the complex and varied effects that these manipulations can have on neuronal dynamics, the resulting changes in cortical activity account for accompanying changes in behavioral acuity. SIGNIFICANCE STATEMENT Excitatory and inhibitory interactions determine stimulus specificity and tuning in sensory cortex, thereby controlling perceptual discrimination acuity. Modeling has predicted that suppressing the activity of inhibitory neurons can lead to increased or, paradoxically, decreased excitatory activity depending on the architecture of the network. Here, we capitalized on differences between subjects to test whether suppressing/activating inhibition and excitation can in fact exhibit such paradoxical effects for both stimulus sensitivity and behavioral discriminability. Indeed, the same optogenetic manipulation in the auditory cortex of different mice could improve or impair frequency discrimination acuity, predictable from the effects on cortical responses to tones. The same manipulations sometimes produced opposite changes in the behavior of different individuals, supporting theoretical predictions for inhibition-stabilized networks.

Interactions between sensory pathways such as the visual and auditory systems are known to occur in the brain, but where they first occur is uncertain. Here, we show a multimodal interaction evident at the eardrum. Ear canal microphone measurements in humans ( n = 19 ears in 16 subjects) and monkeys ( n = 5 ears in three subjects) performing a saccadic eye movement task to visual targets indicated that the eardrum moves in conjunction with the eye movement. The eardrum motion was oscillatory and began as early as 10 ms before saccade onset in humans or with saccade onset in monkeys. These eardrum movements, which we dub eye movement-related eardrum oscillations (EMREOs), occurred in the absence of a sound stimulus. The amplitude and phase of the EMREOs depended on the direction and horizontal amplitude of the saccade. They lasted throughout the saccade and well into subsequent periods of steady fixation. We discuss the possibility that the mechanisms underlying EMREOs create eye movement-related binaural cues that may aid the brain in evaluating the relationship between visual and auditory stimulus locations as the eyes move.

Age-related hearing loss (ARHL) is the most common sensory deficit in the elderly. The disease has a multifactorial etiology with both environmental and genetic factors involved being largely unknown. SLC7A8/SLC3A2 heterodimer is a neutral amino acid exchanger. Here, we demonstrated that SLC7A8 is expressed in the mouse inner ear and that its ablation resulted in ARHL, due to the damage of different cochlear structures. These findings make SLC7A8 transporter a strong candidate for ARHL in humans. Thus, a screening of a cohort of ARHL patients and controls was carried out revealing several variants in SLC7A8 , whose role was further investigated by in vitro functional studies. Significant decreases in SLC7A8 transport activity was detected for patient’s variants (p.Val302Ile, p.Arg418His, p.Thr402Met and p.Val460Glu) further supporting a causative role for SLC7A8 in ARHL. Moreover, our preliminary data suggest that a relevant proportion of ARHL cases could be explained by SLC7A8 mutations.

Cortical sensory maps are remodeled during early life to adapt to the surrounding environment. Both sensory and contextual signals are important for induction of this plasticity, but how these signals converge to sculpt developing thalamocortical circuits remains largely unknown. Here we show that layer 1 (L1) of primary auditory cortex (A1) is a key hub where neuromodulatory and topographically organized thalamic inputs meet to tune the cortical layers below. Inhibitory interneurons in L1 send narrowly descending projections to differentially modulate thalamic drive to pyramidal and parvalbumin-expressing (PV) cells in L4, creating brief windows of intracolumnar activation. Silencing of L1 (but not VIP-expressing) cells abolishes map plasticity during the tonotopic critical period. Developmental transitions in nicotinic acetylcholine receptor (nAChR) sensitivity in these cells caused by Lynx1 protein can be overridden to extend critical-period closure. Notably, thalamocortical maps in L1 are themselves stable, and serve as a scaffold for cortical plasticity throughout life.

Purpose The purpose of this study is to examine talker differences for subjectively rated speech clarity in clear versus conversational speech, to determine whether ratings differ for young adults with normal hearing (YNH listeners) and older adults with hearing impairment (OHI listeners), and to explore effects of certain talker characteristics (e.g., gender) on perceived clarity. Relationships among clarity ratings and other speech perceptual and acoustic measures were also explored. Method Twenty-one YNH and 15 OHI listeners rated clear and conversational sentences produced by 41 talkers on a scale of 1 ( lowest possible clarity ) to 7 ( highest possible clarity ). Results While clarity ratings varied significantly among talkers, listeners rated clear speech significantly clearer than conversational speech for all but 1 talker. OHI and YNH listeners gave similar ratings for conversational speech, but ratings for clear speech were significantly higher for OHI listeners. Talker gender effects differed for YNH and OHI listeners. Ratings of clear speech varied among subgroups of talkers with different amounts of experience talking to people with hearing loss. Conclusions Perceived clarity varies widely among talkers, but nearly all produce clear speech that sounds significantly clearer than their conversational speech. Few differences were seen between OHI and YNH listeners except the effect of talker gender.

Researchers have often utilized the classic Stroop task as a measure of selective attention processes. While it is largely agreed upon that semantic interference plays a role in the classic task, the role of attentional processes is less clear. The picture is further muddied when variations on the classic task are used. For example, the cross-modal Stroop task, in which one names the color of visual items while ignoring distracting auditory color words, typically leads to smaller sized interference effects and little or no facilitation when compared to the classic task. Furthermore, relationship(s) with working memory capacity have only been found in the classic version. We examined whether these differences are due to a methodological factor; namely, spatial integration versus separation of the target and distractor locations. We conducted four experiments manipulating the location of auditory distractors within the cross-modal Stroop task, and found that the location of the distractors had little to no impact on the size of the effect. This lack of an effect of location implies that the mechanisms contributing to the cross-modal Stroop effect are not the same as those of the classic Stroop effect, and that the role of spatial attention in cross-modal Stroop is limited. The implications of a unique role for auditory distractors is considered as well, and supports the conclusion that interference in the cross-modal Stroop effect is the result of a combination of semantic interference and modality-specific interference.

In the primary auditory cortex (A1), neuronal ensembles are activated relative to anticipated sound events following rhythmic stimulation, but whether the echo responses of the neurons are related to their frequency selectivity remains unknown. Therefore, we used in vivo two-photon Ca 2+ imaging to record the neuronal activities in the mouse A1 to elucidate the relationship between their echo responses and frequency selectivity. We confirmed the presence of echo responses in a subgroup of mouse Layer 2/3 A1 neurons following a train of rhythmic pure tone stimulation. After testing with a range of frequencies, we found that these echo responses occurred preferentially close to the best frequencies of the neurons. The local organization of the echo responses of the neurons was heterogeneous in the A1. Therefore, these results indicate that the observed echo responses of neurons within A1 are highly related to their frequency selectivity.

The neurodevelopmental disorder Angelman syndrome (AS) is characterized by intellectual disability, motor dysfunction, distinct behavioral aspects, and epilepsy. AS is caused by a loss of the maternally expressed UBE3A gene, and many of the symptoms are recapitulated in a Ube3a mouse model of this syndrome. At the cellular level, changes in the axon initial segment (AIS) have been reported, and changes in vesicle cycling have indicated the presence of presynaptic deficits. Here we studied the role of UBE3A in the auditory system by recording synaptic transmission at the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) through in vivo whole cell and juxtacellular recordings. We show that MNTB principal neurons in Ube3a mice exhibit a hyperpolarized resting membrane potential, an increased action potential (AP) amplitude and a decreased AP half width. Moreover, both the pre- and postsynaptic AP in the calyx of Held synapse of Ube3a mice showed significantly faster recovery from spike depression. An increase in AIS length was observed in the principal MNTB neurons of Ube3a mice, providing a possible substrate for these gain-of-function changes. Apart from the effect on APs, we also observed that EPSPs showed decreased short-term synaptic depression (STD) during long sound stimulations in AS mice, and faster recovery from STD following these tones, which is suggestive of a presynaptic gain-of-function. Our findings thus provide in vivo evidence that UBE3A plays a critical role in controlling synaptic transmission and excitability at excitatory synapses.

Fischer 344 (F344) rats represent a strain that is frequently used as a model for fast aging. In this study, we systematically compare the hearing function during aging in male and female F344 rats, by recording auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). In addition to this, the functional parameters are correlated with the cochlear histology. The parameters of the hearing function were not different in the young (3-month-old) male and female F344 rats; the gender differences occurred only in adult and aged animals. In 8-24-month-old males, the ABR thresholds were higher and the ABR amplitudes were smaller than those measured in females of the same age. There were no gender differences in the neural adaptation tested by recording ABRs, elicited by a series of clicks with varying inter-click interval (ICI). Amplitudes of DPOAEs in both the males and females decreased with age, but in the males, the decrease of DPOAE amplitudes was faster. In males older than 20 months, the DPOAEs were practically absent, whereas in 20-24-month-old females, the DPOAEs were still measurable. There were no gender differences in the number of surviving outer hair cells (OHC) and the number of inner hair cell ribbon synapses in aged animals. The main difference was found in the stria vascularis (SV). Whereas the SV was well preserved in females up to the age of 24 months, in most of the age-matched males the SV was evidently deteriorated. The results demonstrate more pronounced age-related changes in the cochlear morphology, hearing thresholds, ABR amplitudes and DPOAE amplitudes in F344 males compared with females.

This report explores the consequences of acoustic overexposures on hearing in noisy environments for two macaque monkeys trained to perform a reaction time detection task using a Go/No-Go lever release paradigm. Behavioral and non-invasive physiological assessments were obtained before and after narrowband noise exposure. Physiological measurements showed elevated auditory brainstem response (ABR) thresholds and absent distortion product otoacoustic emissions (DPOAEs) post-exposure relative to pre-exposure. Audiograms revealed frequency specific increases in tone detection thresholds, with the greatest increases at the exposure band frequency and higher. Masked detection was affected in a similar frequency specific manner: threshold shift rates (change of masked threshold per dB increase in noise level) were lower than pre-exposure values at frequencies higher than the exposure band. Detection thresholds in sinusoidally amplitude modulated (SAM) noise post-exposure showed no difference from those in unmodulated noise, whereas pre-exposure masked detection thresholds were lower in the presence of SAM noise compared to unmodulated noise. These frequency-dependent results were correlated with cochlear histopathological changes in monkeys that underwent similar noise exposure. These results reveal that behavioral and physiological effects of noise exposure in macaques are similar to those seen in humans and provide preliminary information on the relationship between noise exposure, cochlear pathology and perceptual changes in hearing within individual subjects.