Publications using TDT

Age-related hearing loss (presbyacusis) is the most common type of hearing impairment. One of the most consistent pathological changes seen in presbyacusis is the loss of spiral ganglion neurons (SGNs). Defining the cellular and molecular basis of SGN degeneration in the human inner ear is critical to gaining a better understanding of the pathophysiology of presbyacusis. However, information on age-related cellular and molecular alterations in the human spiral ganglion remains scant, owing to the very limited availably of human specimens suitable for high resolution morphological and molecular analysis. This study aimed at defining age-related alterations in the auditory nerve in human temporal bones and determining if immunostaining for myelin basic protein (MBP) can be used as an alternative approach to electron microscopy for evaluating myelin degeneration. For comparative purposes, we evaluated ultrastructural alternations and changes in MBP immunostaining in aging CBA/CaJ mice. We then examined 13 temporal bones from 10 human donors, including 4 adults aged 38-46 years (middle-aged group) and 6 adults aged 63-91 years (older group). Similar to the mouse, intense immunostaining of MBP was present throughout the auditory nerve of the middle-aged human donors. Significant declines in MBP immunoreactivity and losses of MBP(+) auditory nerve fibers were observed in the spiral ganglia of both the older human and aged mouse ears. This study demonstrates that immunostaining for MBP in combination with confocal microscopy provides a sensitive, reliable, and efficient method for assessing alterations of myelin sheaths in the auditory nerve. The results also suggest that myelin degeneration may play a critical role in the SGN loss and the subsequent decline of the auditory nerve function in presbyacusis.

Sensory experience in early postnatal life shapes neuronal connections in the brain. Here we report that the local synthesis of brain-derived neurotrophic factor (BDNF) in dendrites plays an important role in this process. We found that dendritic spines of layer 2/3 pyramidal neurons of the visual cortex in mutant mice lacking dendritic Bdnf mRNA and thus local BDNF synthesis were normal at 3 weeks of age, but thinner, longer, and more closely spaced (morphological features of immaturity) at 4 months of age than in wild-type (WT) littermates. Layer 2/3 of the visual cortex in these mutant animals also had fewer GABAergic presynaptic terminals at both ages. The overall size and shape of dendritic arbors were, however, similar in mutant and WT mice at both ages. By using optical imaging of intrinsic signals and single-unit recordings, we found that mutant animals failed to recover cortical responsiveness following monocular deprivation (MD) during the critical period, although they displayed normally the competitive loss of responsiveness to an eye briefly deprived of vision. Furthermore, MD still induced a loss of responsiveness to the closed eye in adult mutant mice, but not in adult WT mice. These results indicate that dendritic BDNF synthesis is required for spine pruning, late-phase spine maturation, and recovery of cortical responsiveness following sensory deprivation. They also suggest that maturation of dendritic spines is required for the maintenance of cortical responsiveness following sensory deprivation in adulthood.

The structural homeostasis of the cochlear hair cell membrane is critical for all aspects of sensory transduction, but the regulation of its maintenance is not well understood. In this report, we analyzed the cochlear hair cells of mice with specific deletion of myosin light chain kinase (MLCK) in inner hair cells. MLCK-deficient mice showed impaired hearing, with a 5- to 14-dB rise in the auditory brainstem response (ABR) thresholds to clicks and tones of different frequencies and a significant decrease in the amplitude of the ABR waves. The mutant inner hair cells produced several ball-like structures around the hair bundles in vivo, indicating impaired membrane stability. Inner hair cells isolated from the knockout mice consistently displayed less resistance to hypoosmotic solution and less membrane F-actin. Myosin light-chain phosphorylation was also reduced in the mutated inner hair cells. Our results suggest that MLCK is necessary for maintaining the membrane stability of inner hair cells.

Judgments of whether a sinusoidal probe is higher or lower in frequency than the closest partial (“target”) in a multi-partial complex are improved when the target is pulsed on and off. These experiments explored the contribution of reduction in perceptual confusion and recovery from adaptation to this effect. In experiment 1, all partials except the target were replaced by noise to reduce perceptual confusion. Performance was much better than when the background was composed of multiple partials. When the level of the target was reduced to avoid ceiling effects, no effect of pulsing the target occurred. In experiment 2, the target and background partials were irregularly and independently amplitude modulated. This gave a large effect of pulsing the target, suggesting that if recovery from adaptation contributes to the effect, amplitude fluctuations do not prevent this. In experiment 3, the background was composed of multiple steady partials, but the target was irregularly amplitude modulated. This gave better performance than when the target was unmodulated and a moderate effect of pulsing the target. It is argued that when the target and background are steady tones, pulsing the target may result both in reduction of perceptual confusion and recovery from adaptation.

Prosaposin, a precursor of four glycoprotein activators (saposin A, B, C and D) for lysosomal hydrolases, has previously been shown to be important for normal adult cochlear innervation and the maintenance of normal hearing. In these studies, we now investigate prosaposin in normal vestibular epithelium and the functional impairment of balance caused by prosaposin ablation. In normal mice, prosaposin is localized to all 3 vestibular end-organs (ampullae, saccule, and utricle) and Scarpa's ganglion by RT-PCR, Western blot analysis and immunofluorescence. Ablation of prosaposin function caused severe vestibular dysfunction on a battery of behavioral tasks. Histologically, the KO mice demonstrated an exuberant cellular proliferation below the vestibular hair cells with disruption of the supporting cells. Electron microscopy further demonstrated inclusion bodies and cellular proliferation disturbing the normal neuroepithelial structure of the vestibular end-organs. Lastly, immunofluorescence (neurofilament 200 and synaptophysin) staining suggests that this cellular proliferation corresponds to afferent and efferent neuronal overgrowth. These data suggest that prosaposin plays a role not only in the maintenance of normal hearing but also an important role in the neuronal maturation processes of the vestibular sensory epithelium and the maintenance of normal vestibular system function.

Signal honesty may be compromised when heightened competition provides incentive for signal exaggeration. Some degree of honesty might be maintained by intrinsic handicap costs on signalling or through imposition of extrinsic costs, such as social punishment of low quality cheaters. Thus, theory predicts a delicate balance between signal enhancement and signal reliability that varies with degree of social competition, handicap cost, and social cost. We investigated whether male sexual signals of the electric fish Brachyhypopomus gauderio would become less reliable predictors of body length when competition provides incentives for males to boost electric signal amplitude. As expected, social competition under natural field conditions and in controlled lab experiments drove males to enhance their signals. However, signal enhancement improved the reliability of the information conveyed by the signal, as revealed in the tightening of the relationship between signal amplitude and body length. Signal augmentation in male B. gauderio was independent of body length, and thus appeared not to be curtailed through punishment of low quality (small) individuals. Rather, all individuals boosted their signals under high competition, but those whose signals were farthest from the predicted value under low competition boosted signal amplitude the most. By elimination, intrinsic handicap cost of signal production, rather than extrinsic social cost, appears to be the basis for the unexpected reinforcement of electric signal honesty under social competition. Signal modulation may provide its greatest advantage to the signaller as a mechanism for handicap disposal under low competition rather than as a mechanism for exaggeration of quality under high competition.

Purpose In this article, a new signal-processing algorithm is proposed and evaluated for the suppression of the combined effects of reverberation and noise. Method The proposed algorithm decomposes, on a short-term basis (every 20 ms), the reverberant stimuli into a number of channels and retains only a subset of the channels satisfying a signal-to-reverberant ratio (SRR) criterion. The construction of this criterion assumes access to a priori knowledge of the target (anechoic) signal, and the aim of this study was to assess the full potential of the proposed channel-selection algorithm, assuming that this criterion could be estimated accurately. Listening tests with normal-hearing listeners were conducted to assess the performance of the proposed algorithm in highly reverberant conditions ( T 60 = 1.0 s), which included additive noise at 0 and 5 dB signal-to-noise ratios (SNRs). Results A substantial gain in intelligibility was obtained in both reverberant and combined reverberant and noise conditions. The mean intelligibility scores improved by 44 and 33 percentage points at 0 and 5 dB SNR reverberation + noise conditions. Feature analysis of the consonant confusion matrices revealed that the transmission of voicing information was most negatively affected, followed by manner and place of articulation. Conclusions The proposed algorithm produced substantial gains in intelligibility, and this benefit was attributed to the ability of the proposed SRR criterion to detect accurately voiced or unvoiced boundaries. It was postulated that detection of those boundaries is critical for better perception of voicing information and manner of articulation.

Purpose In this experiment, a single comparison stimulus was developed as a reference in a perceptual matching task for the quantification of breathy voice quality. Perceptual judgments of a set of synthetic voice samples were compared to previous data obtained using multiple comparison stimuli “customized” for different voices (Patel, Shrivastav, & Eddins, 2010). Method Five male and 5 female samples of the vowel /a/ were selected from the Kay Elemetrics Disordered Voice Database and resynthesized using a Klatt synthesizer. Eleven samples were created for each base voice by manipulating the aspiration noise level. Five samples from each continuum were evaluated in a perceptual matching task in which a single sawtooth and noise comparison stimulus was used to obtain breathiness judgments. Linear regression was used to compare measurements obtained using the new comparison stimulus against the customized comparison stimuli. Results Results indicated that the noncustomized sawtooth comparison provides reliability and perceptual distances between stimuli similar to those obtained using customized comparison stimuli. Conclusion A single-variable matching task using a single comparison stimulus can be used to obtain perceptual estimates of breathiness across voices and experiments in a laboratory setting. This technique will help develop models of voice-quality perception.

Objective: Perceptual sensitivities are malleable via learning, even in adults. We trained adults to discriminate complex sounds (periodic, frequency-modulated sweep trains) using two different training procedures, and used psychoacoustic tests and evoked potential measures (the N1-P2 complex) to assess changes in both perceptual and neural sensitivities. Methods: Training took place either on a single day, or daily across eight days, and involved discrimination of pairs of stimuli using a single-interval, forced-choice task. In some participants, training started with dissimilar pairs that became progressively more similar across sessions, whereas in others training was constant, involving only one, highly similar, stimulus pair. Results: Participants were better able to discriminate the complex sounds after training, particularly after progressive training, and the evoked potentials elicited by some of the sounds increased in amplitude following training. Significant amplitude changes were restricted to the P2 peak. Conclusions: Our findings indicate that changes in perceptual sensitivities parallel enhanced neural processing. Significance: These results are consistent with the proposal that changes in perceptual abilities arise from the brain's capacity to adaptively modify cortical representations of sensory stimuli, and that different training regimens can lead to differences in cortical sensitivities, even after relatively short periods of training.

Sound is detected and converted into electrical signals within the ear. The cochlea not only acts as a passive detector of sound, however, but can also produce tones itself. These otoacoustic emissions are a striking manifestation of the cochlea's mechanical active process. A controversy remains of how these mechanical signals propagate back to the middle ear, from which they are emitted as sound. Here, we combine theoretical and experimental studies to show that mechanical signals can be transmitted by waves on Reissner's membrane, an elastic structure within the cochlea. We develop a theory for wave propagation on Reissner's membrane and its role in otoacoustic emissions. Employing a scanning laser interferometer, we measure traveling waves on Reissner's membrane in the gerbil, guinea pig, and chinchilla. The results are in accord with the theory and thus support a role for Reissner's membrane in otoacoustic emissions.

This study tested the hypothesis that the reduction in spatial release from masking (SRM) resulting from sensorineural hearing loss in competing speech mixtures is influenced by the characteristics of the interfering speech. A frontal speech target was presented simultaneously with two intelligible or two time-reversed (unintelligible) speech maskers that were either colocated with the target or were symmetrically separated from the target in the horizontal plane. The difference in SRM between listeners with hearing impairment and listeners with normal hearing was substantially larger for the forward maskers (deficit of 5.8 dB) than for the reversed maskers (deficit of 1.6 dB). This was driven by the fact that all listeners, regardless of hearing abilities, performed similarly (and poorly) in the colocated condition with intelligible maskers. The same conditions were then tested in listeners with normal hearing using headphone stimuli that were degraded by noise vocoding. Reducing the number of available spectral channels systematically reduced the measured SRM, and again, more so for forward (reduction of 3.8 dB) than for reversed speech maskers (reduction of 1.8 dB). The results suggest that non-spatial factors can strongly influence both the magnitude of SRM and the apparent deficit in SRM for listeners with impaired hearing.

Studies on the precedence effect typically utilize a two-source paradigm, which is not realistic relative to real world situations where multiple reflections exist. A step closer to multiple-reflection situations was studied using a three-source paradigm. Discrimination of interaural time differences (ITDs) was measured for one-, two-, and three-source stimuli, using clicks presented over headphones. The ITD was varied in either the first, second, or the third source. The inter-source intervals ranged from 0–130 ms. A perceptual weighting model was extendedto incorporate the three-source stimuli and used to interpret the data. The effect of adding a third source could mostly, but not entirely, be understood by the interaction of effects observed in the precedence effect with two sources. Specifically, for delays between 1 and 8 ms, the ITD information of prior sources was typically weighted more heavily than subsequent sources. For delays greater than 8 ms, subsequent sources were typically weighted slightly more heavily than prior sources. However, there were specific conditions that showed a more complex interaction between the sources. These findings suggest that the two-source paradigm provides a strong basis for understanding how the auditory system processes reflections in spatial hearing tasks.

The glutamate transporter GLT-1 is responsible for the largest proportion of total glutamate transport. Recently, it has been demonstrated that ceftriaxone (CEF) robustly increases GLT-1 expression. In addition, physiological studies have shown that GLT-1 up-regulation strongly affects synaptic plasticity, and leads to an impairment of the prepulse inhibition, a simple form of information processing, thus suggesting that GLT-1 over-expression may lead to dysfunctions of large populations of neurons. To test this possibility, we assessed whether CEF affects cortical electrical activity by using chronic electroencephalographic (EEG) recordings in male WKY rats. Spectral analysis showed that 8 days of CEF treatment resulted in a delayed reduction in EEG theta power (7-9 Hz) in both frontal and parietal derivations. This decrease peaked at day 10, i.e., 2 days after the end of treatment, and disappeared by day 16. In addition, we found that the same CEF treatment increased motor activity, especially when EEG changes are more prominent. Taken together, these data indicate that GLT-1 up-regulation, by modulating glutamatergic transmission, impairs the activity of widespread neural circuits. In addition, the increased motor activity and prepulse inhibition alterations previously described suggest that neural circuits involved in sensorimotor control are particularly sensitive to GLT-1 up-regulation.

Background: Animals that communicate by sound face the problem that the signals arriving at the receiver often are degraded and masked by noise. Frequency filters in the receiver's auditory system may improve the signal-to-noise ratio (SNR) by excluding parts of the spectrum which are not occupied by the species-specific signals. This solution, however, is hardly amenable to species that produce broad band signals or have ears with broad frequency tuning. In mammals auditory filters exist that work in the temporal domain of amplitude modulations (AM). Do insects also use this type of filtering? Principal findings: Combining behavioural and neurophysiological experiments we investigated whether AM filters may improve the recognition of masked communication signals in grasshoppers. The AM pattern of the sound, its envelope, is crucial for signal recognition in these animals. We degraded the species-specific song by adding random fluctuations to its envelope. Six noise bands were used that differed in their overlap with the spectral content of the song envelope. If AM filters contribute to reduced masking, signal recognition should depend on the degree of overlap between the song envelope spectrum and the noise spectra. Contrary to this prediction, the resistance against signal degradation was the same for five of six masker bands. Most remarkably, the band with the strongest frequency overlap to the natural song envelope (0-100 Hz) impaired acceptance of degraded signals the least. To assess the noise filter capacities of single auditory neurons, the changes of spike trains as a function of the masking level were assessed. Increasing levels of signal degradation in different frequency bands led to similar changes in the spike trains in most neurones. Conclusions: There is no indication that auditory neurones of grasshoppers are specialized to improve the SNR with respect to the pattern of amplitude modulations.

The ability to detect novel sounds in a complex acoustic context is crucial for survival. Neurons from midbrain through cortical levels adapt to repetitive stimuli, while maintaining responsiveness to rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). The site of origin and mechanism of SSA are currently unknown. We used microiontophoretic application of gabazine to examine the role of GABA(A)-mediated inhibition in SSA in the inferior colliculus, the midbrain center for auditory processing. We found that gabazine slowed down the process of adaptation to high probability stimuli but did not abolish it, with response magnitude and latency still depending on the probability of the stimulus. Blocking GABA(A) receptors increased the firing rate to high and low probability stimuli, but did not completely equalize the responses. Together, these findings suggest that GABA(A)-mediated inhibition acts as a gain control mechanism that enhances SSA by modifying the responsiveness of the neuron.

Background: It is commonly assumed that the cochlear microphonic potential (CM) recorded from the round window (RW) is generated at the cochlear base. Based on this assumption, the low-frequency RW CM has been measured for evaluating the integrity of mechanoelectrical transduction of outer hair cells at the cochlear base and for studying sound propagation inside the cochlea. However, the group delay and the origin of the low-frequency RW CM have not been demonstrated experimentally. Methodology/principal findings: This study quantified the intra-cochlear group delay of the RW CM by measuring RW CM and vibrations at the stapes and basilar membrane in gerbils. At low sound levels, the RW CM showed a significant group delay and a nonlinear growth at frequencies below 2 kHz. However, at high sound levels or at frequencies above 2 kHz, the RW CM magnitude increased proportionally with sound pressure, and the CM phase in respect to the stapes showed no significant group delay. After the local application of tetrodotoxin the RW CM below 2 kHz became linear and showed a negligible group delay. In contrast to RW CM phase, the BM vibration measured at location ∼2.5 mm from the base showed high sensitivity, sharp tuning, and nonlinearity with a frequency-dependent group delay. At low or intermediate sound levels, low-frequency RW CMs were suppressed by an additional tone near the probe-tone frequency while, at high sound levels, they were partially suppressed only at high frequencies. Conclusions/significance: We conclude that the group delay of the RW CM provides no temporal information on the wave propagation inside the cochlea, and that significant group delay of low-frequency CMs results from the auditory nerve neurophonic potential. Suppression data demonstrate that the generation site of the low-frequency RW CM shifts from apex to base as the probe-tone level increases.

Cognition and behavior depend on the precise placement and interconnection of complex ensembles of neurons in cerebral cortex. Mutations that disrupt migration of immature neurons from the ventricular zone to the cortical plate have provided major insight into mechanisms of brain development and disease. We have discovered a new and highly penetrant spontaneous mutation that leads to large nodular bilateral subcortical heterotopias with partial callosal agenesis. The mutant phenotype was first detected in a colony of fully inbred BXD29 mice already known to harbor a mutation in Tlr4. Neurons confined to the heterotopias are mainly born in midgestation to late gestation and would normally have migrated into layers 2-4 of overlying neocortex. Callosal cross-sectional area and fiber number are reduced up to 50% compared with coisogenic wildtype BXD29 substrain controls. Mutants have a pronounced and highly selective defect in rapid auditory processing. The segregation pattern of the mutant phenotype is most consistent with a two-locus autosomal recessive model, and selective genotyping definitively rules out the Tlr4 mutation as a cause. The discovery of a novel mutation with strong pleiotropic anatomical and behavioral effects provides an important new resource for dissecting molecular mechanisms and functional consequences of errors of neuronal migration.

Background: Tinnitus is a frequent, debilitating hearing disorder associated with severe emotional and psychological suffering. Although a link between stress and tinnitus has been widely recognized, the empirical evidence is scant. Our aims were to test for dysregulation of the stress-related hypothalamus-pituitary adrenal (HPA) axis in tinnitus and to examine ear sensitivity variations with cortisol manipulation. Methods: Twenty-one tinnitus participants and 21 controls comparable in age, education, and overall health status but without tinnitus underwent basal cortisol assessments on three non-consecutive days and took 0.5 mg of dexamethasone (DEX) at 23:00 on the first day. Cortisol levels were measured hourly the next morning. Detection and discomfort hearing thresholds were measured before and after dexamethasone suppression test. Results: Both groups displayed similar basal cortisol levels, but tinnitus participants showed stronger and longer-lasting cortisol suppression after DEX administration. Suppression was unrelated to hearing loss. Discomfort threshold was lower after cortisol suppression in tinnitus ears. Conclusions: Our findings suggest heightened glucocorticoid sensitivity in tinnitus in terms of an abnormally strong glucocorticoid receptor (GR)-mediated HPA-axis feedback (despite a normal mineralocorticoid receptor (MR)-mediated tone) and lower tolerance for sound loudness with suppressed cortisol levels. Long-term stress exposure and its deleterious effects therefore constitute an important predisposing factor for, or a significant pathological consequence of, this debilitating hearing disorder.

Turtles, like other amphibious animals, face a trade-off between terrestrial and aquatic hearing. We used laser vibrometry and auditory brainstem responses to measure their sensitivity to vibration stimuli and to airborne versus underwater sound. Turtles are most sensitive to sound underwater, and their sensitivity depends on the large middle ear, which has a compliant tympanic disc attached to the columella. Behind the disc, the middle ear is a large air-filled cavity with a volume of approximately 0.5 ml and a resonance frequency of approximately 500 Hz underwater. Laser vibrometry measurements underwater showed peak vibrations at 500–600 Hz with a maximum of 300 µm s −1 Pa −1 , approximately 100 times more than the surrounding water. In air, the auditory brainstem response audiogram showed a best sensitivity to sound of 300–500 Hz. Audiograms before and after removing the skin covering reveal that the cartilaginous tympanic disc shows unchanged sensitivity, indicating that the tympanic disc, and not the overlying skin, is the key sound receiver. If air and water thresholds are compared in terms of sound intensity, thresholds in water are approximately 20–30 dB lower than in air. Therefore, this tympanic ear is specialized for underwater hearing, most probably because sound-induced pulsations of the air in the middle ear cavity drive the tympanic disc.

Acoustically communicating animals often have to cope with ambient noise that has the potential to interfere with the perception of conspecific signals. Here we use the synchronous display of mating signals in males of the tropical katydid Mecopoda elongata in order to assess the influence of nocturnal rainforest noise on signal perception. Loud background noise may disturb chorus synchrony either by masking the signals of males or by interaction of noisy events with the song oscillator. Phase-locked synchrony of males was studied under various signal-to-noise ratios (SNRs) using either native noise or the audio component of noise (<9 kHz). Synchronous entrainment was lost at a SNR of -3 dB when native noise was used, whereas with the audio component still 50% of chirp periods matched the pacer period at a SNR of -7 dB. Since the chirp period of solo singing males remained almost unaffected by noise, our results suggest that masking interference limits chorus synchrony by rendering conspecific signals ambiguous. Further, entrainment with periodic artificial signals indicates that synchrony is achieved by ignoring heterospecific signals and attending to a conspecific signal period. Additionally, the encoding of conspecific chirps was studied in an auditory neuron under the same background noise regimes.