Correction: Contrasting mechanisms for hidden hearing loss: Synaptopathy vs myelin defects.

[This corrects the article DOI: 10.1371/journal.pcbi.1008499.].

Contrasting mechanisms for hidden hearing loss: Synaptopathy vs myelin defects.

Hidden hearing loss (HHL) is an auditory neuropathy characterized by normal hearing thresholds but reduced amplitudes of the sound-evoked auditory nerve compound action potential (CAP). In animal models, HHL can be caused by moderate noise exposure or aging, which induces loss of inner hair cell (IHC) synapses. In contrast, recent evidence has shown that transient loss of cochlear Schwann cells also causes permanent auditory deficits in mice with similarities to HHL. Histological analysis of the cochlea after auditory nerve remyelination showed a permanent disruption of the myelination patterns at the heminode of type I spiral ganglion neuron (SGN) peripheral terminals, suggesting that this defect could be contributing to HHL. To shed light on the mechanisms of different HHL scenarios observed in animals and to test their impact on type I SGN activity, we constructed a reduced biophysical model for a population of SGN peripheral axons whose activity is driven by a well-accepted model of cochlear sound processing. We found that the amplitudes of simulated sound-evoked SGN CAPs are lower and have greater latencies when heminodes are disorganized, i.e. they occur at different distances from the hair cell rather than at the same distance as in the normal cochlea. These results confirm that disruption of heminode positions causes desynchronization of SGN spikes leading to a loss of temporal resolution and reduction of the sound-evoked SGN CAP. Another mechanism resulting in HHL is loss of IHC synapses, i.e., synaptopathy. For comparison, we simulated synaptopathy by removing high threshold IHC-SGN synapses and found that the amplitude of simulated sound-evoked SGN CAPs decreases while latencies remain unchanged, as has been observed in noise exposed animals. Thus, model results illuminate diverse disruptions caused by synaptopathy and demyelination on neural activity in auditory processing that contribute to HHL as observed in animal models and that can contribute to perceptual deficits induced by nerve damage in humans.

Broadband nonreciprocal linear acoustics through a non-local active metamaterial.

The ability to create linear systems that manifest broadband nonreciprocal wave propagation would provide for exquisite control over acoustic signals for electronic filtering in communication and noise control. Acoustic nonreciprocity has predominately been achieved by approaches that introduce nonlinear interaction, mean-flow biasing, smart skins, and spatio-temporal parametric modulation into the system. Each approach suffers from at least one of the following drawbacks: the introduction of modulation tones, narrow band filtering, and the interruption of mean flow in fluid acoustics. We now show that an acoustic media that is non-local and active provides a new means to break reciprocity in a linear fashion without these deleterious effects. We realize this media using a distributed network of interlaced subwavelength sensor-actuator pairs with unidirectional signal transport. We exploit this new design space to create a stable metamaterial with non-even dispersion relations and electronically tunable nonreciprocal behavior over a broad range of frequencies.

Unified cochlear model for low- and high-frequency mammalian hearing.

The spatial variations of the intricate cytoarchitecture, fluid scalae, and mechano-electric transduction in the mammalian cochlea have long been postulated to provide the organ with the ability to perform a real-time, time-frequency processing of sound. However, the precise manner by which this tripartite coupling enables the exquisite cochlear filtering has yet to be articulated in a base-to-apex mathematical model. Moreover, while sound-evoked tuning curves derived from mechanical gains are excellent surrogates for auditory nerve fiber thresholds at the base of the cochlea, this correlation fails at the apex. The key factors influencing the divergence of both mechanical and neural tuning at the apex, as well as the spatial variation of mechanical tuning, are incompletely understood. We develop a model that shows that the mechanical effects arising from the combination of the taper of the cochlear scalae and the spatial variation of the cytoarchitecture of the cochlea provide robust mechanisms that modulate the outer hair cell-mediated active response and provide the basis for the transition of the mechanical gain spectra along the cochlear spiral. Further, the model predicts that the neural tuning at the base is primarily governed by the mechanical filtering of the cochlear partition. At the apex, microscale fluid dynamics and nanoscale channel dynamics must also be invoked to describe the threshold neural tuning for low frequencies. Overall, the model delineates a physiological basis for the difference between basal and apical gain seen in experiments and provides a coherent description of high- and low-frequency cochlear tuning.

The Competition between the Noise and Shear Motion Sensitivity of Cochlear Inner Hair Cell Stereocilia.

Acoustical excitation of the organ of Corti induces radial fluid flow in the subtectorial space (STS) that excites the hair bundles (HBs) of the sensory inner hair cell of the mammalian cochlea. The inner hair cell HBs are bathed in endolymphatic fluid filling a thin gap in the STS between the tectorial membrane and the reticular lamina. According to the fluctuation dissipation theorem, the fluid viscosity gives rise to mechanical fluctuations that are transduced into current noise. Conversely, the stochastic fluctuations of the mechanically gated channels of the HBs also induce dissipation. We develop an analytic model of the STS complex in a cross section of the gerbil organ of Corti. We predict that the dominant noise at the apex is due to the channel stochasticity whereas viscous effects dominate at the base. The net root mean square fluctuation of the HB motion is estimated to be at least 1.18 nm at the base and 2.72 nm at the apex. By varying the HB height for a fixed STS gap, we find that taller HBs are better sensors with lower thresholds. An integrated active HB model is shown to reduce the hydrodynamic resistance through a cycle-by-cycle power addition through adaptation, reducing the thresholds of hearing, hinting at one potential role for HB activity in mammalian hearing. We determine that a Couette flow approximation in the STS underestimates the dissipation and that modeling the entire STS complex is necessary to correctly predict the low-frequency dissipation in the cochlea. Finally, the difference in the noise budget at the base and the apex of the cochlea indicate that a sensing modality other than the shear motion of the TM that may be used to achieve low-noise acoustic sensing at the apex.