Jaro-Journal of the Association for Research in Otolaryngology最新文献

Purpose: Assessing the contribution of cochlear synaptopathy (CS) to the variability in speech-in-noise intelligibility among individuals remains a challenge. While several studies have proposed biomarkers for CS based on neural phase-locking to the temporal envelope (ENV), fewer have investigated how CS affects the coding of temporal fine structure (TFS), despite its crucial role in speech-in-noise perception. In this study, we specifically examined whether TFS-based markers of CS could be derived from electrophysiological responses and psychophysical detection thresholds of spectral modulation (SM) in a complex tone, which serves as a parametric model of speech.

Methods: We employed an integrated approach, combining psychophysical testing with frequency-following response (FFR) measurements in three groups of participants: young normal-hearing (n = 15, 12 females, age 21 ± 1); older normal-hearing (n = 16, 11 females, age 47 ± 6); and older hearing-impaired (n = 14, 8 females, age 52 ± 6). We expanded on previous work by assessing phase-locking to both ENV, using a 4-kHz rectangular amplitude-modulated (RAM) tone, and TFS, using a low-frequency (< 1.5 kHz) SM complex tone.

Results: Overall, FFR results showed significant reductions in neural phase-locking to both ENV and TFS components with age and hearing loss. Specifically, the strength of TFS-related FFRs, particularly the component corresponding to the harmonic closest to the peak of the spectral envelope (~ 500 Hz), was negatively correlated with age, even after adjusting for audiometric thresholds. This TFS marker also correlated with ENV-related FFRs derived from the RAM tone, suggesting a shared decline in phase-locking capacity across low and high cochlear frequencies. Computational simulations of the auditory periphery indicated that the observed FFR strength reduction with age is consistent with approximately 50% loss of auditory nerve fibers, aligning with histopathological data. However, the TFS-based FFR marker did not account for variability in speech intelligibility observed in the same participants. Psychophysical measurements showed no age-related effects and were unrelated to the TFS-based FFR marker, highlighting the need for further psychophysical research to establish a behavioral counterpart.

Conclusion: Altogether, our results demonstrate that FFRs to vowel-like stimuli can serve as a complementary electrophysiological marker for assessing neural coding fidelity to stimulus TFS. This approach could provide a valuable tool for better understanding the impact of CS on an important coding dimension for speech-in-noise perception.

Purpose: Cochlear implants (CI) are a highly successful neural prosthesis that can restore hearing in individuals with sensorineural hearing loss. However, the extent of hearing restoration varies widely. Two major factors likely contribute to poor performance: (1) the distances between electrodes and surviving spiral ganglion neurons and (2) the density of those neurons. Reprogramming the CI at a poor electrode-neuron interface, using focused tripolar stimulation or remapping the electrodes, would benefit from understanding the cause of the poor interface.

Methods: We used a cochlear model with simplified geometry and neuronal composition to investigate how the interface affects stimulation thresholds. We then inverted the model to infer electrode distance and neuronal density from monopolar and tripolar threshold values obtained behaviorally. We validated this inverted model for known scenarios of electrode distance and neuronal density. Finally, we assessed the model using data from 18 CI users whose electrode distances were measured from CT imaging.

Results: The inverted model accurately inferred electrode distance and neuronal density for known scenarios. It also reliably reproduced behavioral monopolar and tripolar threshold profiles for CI users, with mean prediction errors within 1 dB for 17/18 subjects. Fits of electrode distance were more variable; accuracy depended on the assumed value of temporal bone resistivity. Twelve subjects had minimum distance error (0.31 mm) using low resistivity (70 Ω-cm) while the others had better fits (0.30 mm) with higher resistivity (250 Ω-cm).

Conclusion: This inverted model shows promise as a simple, practical tool to better assess and understand the electrode-neuron interface.

Purpose: To reduce amplitude variability of auditory evoked potentials (AEPs) we developed a circuit that generates an electric calibration pulse (CalPulse) following each evoking sound presentation. We aim to determine if external CalPulse signals can function as a reliable calibration reference for AEP amplitude measurements.

Methods: The CalPulse circuit was integrated with an AEP recording montage. The amplitude and morphology of two CalPulse signals (square wave and sine wave) was first assessed in vitro with electrodes submerged in saline. Repeatability of the two signals was then compared in vivo using five (3 male/2 female) 4-month-old CBA/CAJ mice and four unique auditory brainstem response (ABR) configurations. Sine wave CalPulse amplitudes were subsequently used to adjust raw ABR wave-1 amplitudes in a sample of 38 (19 male/19 female) CBA/CaJ mice. Variability in adjusted wave-1 amplitudes was compared with raw amplitudes. Measurements were repeated every month for 4 months (8 to 11 months old) to evaluate its potential as a tool to detect age-related changes in auditory function.

Results: Wave quality examinations indicate that both CalPulse signal types are stable in vitro, with the sine wave signal being more repeatable when recorded in vivo. Sine wave CalPulse amplitudes correlated positively with ABR wave-1 amplitudes. Normalizing wave-1 amplitudes with CalPulse measures significantly reduced within-subject variability. Normalized wave-1 amplitudes showed a significant decrease at 10 months of age consistent with age-related cochlear synaptopathy, while uncalibrated wave-1 amplitudes from the same recordings failed to detect this decrease.

Conclusion: Our new calibration circuit can be used to improve diagnostic sensitivity of AEP measures.

Purpose: The otolith organs of the inner ear consist of the utricle and saccule that detect linear acceleration. These organs rely on mechanosensitive hair cells for transduction of signals to the central nervous system. In the murine utricle, about half of the hair cells are born during the first postnatal week. Here, we wanted to explore the role and interaction of the non-epithelial mesenchymal cells with the sensory epithelium and provide a resource for the auditory neurosciences community.

Methods: We utilized full-length Smart-seq2 single-cell RNA sequencing at postnatal days 4 and 6 along with a host of computational methods to infer interactions between the epithelial and non-epithelial compartments of the mouse utricle. We validated these findings using a combination of immunohistochemistry and quantitative multiplex in situ hybridization.

Results: We report diverse cell-cell crosstalk among the 12 annotated cell populations (n = 955 cells) in the developing neonatal mouse utricle, including epithelial and non-epithelial cellular signaling. The mesenchymal cells are the dominant signal senders during the postnatal period. Epithelial to mesenchymal signaling, as well as mesenchymal to epithelial signaling, are quantitatively shown through the TGFβ and pleiotrophin pathways.

Conclusion: This study highlights the dynamic process of postnatal vestibular organ development that relies not only on epithelial cells, but also on crosstalk between spatial compartments and among different cell groups. We further provide a data-rich resource for the inner ear community.

Steady-state auditory evoked potentials are useful for studying the human auditory system and diagnosing hearing disorders. Identifying the generators of these potentials is essential for interpretation of data and for determining appropriate clinical and research applications. Here we infer putative generators of a steady-state potential measured from an electrode on the eardrum and compare this potential with the traditional envelope following response (EFR) measured from an electrode on the high forehead (N = 18, 10 female). We hypothesized that responses from the eardrum electrode would be consistent with an auditory nerve (AN) compound action potential (CAP) evoked by each cycle of the stimulus envelope, resulting in a potential we call CAP_ENV. Steady-state potentials were evoked by a 90 dB peSPL, 3000-Hz puretone carrier whose envelope was modulated by a tone sweep with frequencies from 20 to 160 Hz or 80 to 640 Hz. We calculated group delay to infer potential generators. We also compared the empirically measured CAP_ENV with simulated CAP_ENV from a humanized model of AN responses. Response latencies and model simulations support the interpretation that CAP_ENV is generated by the AN rather than hair cell or brainstem generators for all modulation frequencies tested. Conversely, latencies for the traditional EFR were consistent with a shift from cortical to brainstem generators as the modulation frequency increased from 20 to 200 Hz. We propose that CAP_ENV may be a fruitful tool for assessing AN function in humans with suspected AN fiber loss and/or temporal coding disorders.

Purpose: While the vestibular system is crucial for balance, posture, and stable vision, emerging evidence connects vestibular loss in older adults to spatial cognitive deficits. However, the specific neural pathways remain unclear. This study examines morphometric changes in the entorhinal cortex (ERC) and trans-entorhinal cortex (TEC), key regions in the vestibular spatial cognitive network, with vestibular function.

Methods: This cross-sectional study used T1-weighted MRI images and vestibular physiological data from 103 Baltimore Longitudinal Study of Aging participants (74 males and 29 females). Vestibular function was assessed through the cervical vestibular-evoked myogenic potential (cVEMP), ocular VEMP (oVEMP), and video head-impulse test (vHIT), examining both categorical presence/absence of responses and continuous measures (cVEMP amplitude, oVEMP amplitude, and VOR gain). Morphometric changes in the ERC and TEC were analyzed by examining surface expansions and contractions relative to average shapes.

Results: Reduced saccular function correlated with surface expansion in the left ERC's pro-rhinal, right ERC's intermediate caudal and superior regions, and right TEC's sulcal region. The decreased utricular function was associated with surface contraction in the left lateral TEC, left ERC's anterior sulcal and trans-entorhinal regions, and surface expansion in the lateral region of the left ERC. Reduced canal function showed surface contraction in the right ERC's pro-rhinal and lateral regions and the right TEC's posterior sulcal and trans-entorhinal regions.

Conclusion: These findings highlight the intricate link between vestibular function and ERC/TEC morphology, emphasizing their role in spatial and cognitive abilities. Future research will assess if structural changes due to vestibular loss contribute to cognitive deficits in aging and Alzheimer's disease.

Purpose: A patency at the cochlear basal turn (CBTP) can lead to an abrupt leakage of CSF, known as intraoperative CSF gusher. To date, there is no established technique for predicting an intraoperative CSF gusher. We aim to establish the prevalence, width and anatomical variation of CBTP in patients with and without hearing loss as well as to estimate its association between intraoperative CSF gusher.

Methods: A retrospective review of high-resolution CT images and medical records from 165 pediatric patients (330 ears) was conducted (57 males/108 females). Patients were grouped based on audiometry results: a hearing loss group and healthy controls. The presence and size of CBTP was assessed using multiplanar reconstruction techniques. The incidence of intraoperative CSF gusher was recorded and correlated with the width of CBTP.

Results: Cochlear basal turn patency was found in 44.2% of ears without significant differences between both groups (p = 0.06). Intraoperative CSF gusher occurred in 5.1% of cases, more frequently in ears with inner ear malformations (27.3%). A CBTP larger than 0.75 mm did not predict intraoperative CSF gusher (p = 0.55). Enlarged vestibular aqueduct was significantly the more common malformation in patients with intraoperative CSF gusher (p < 0.01).

Conclusion: Intraoperative CSF gusher highlights the need for reliable imaging predictors. Yet, CBTP alone does not predict this phenomenon, indicating other contributing factors beyond known imaging findings.

Purpose: There are challenges in understanding the biomechanics of the human middle ear, and established methods for studying this system show significant limitations. In this study, we evaluate a novel dynamic imaging technique based on synchrotron X-ray microtomography designed to assess the biomechanical properties of the human middle ear by comparing it to laser-Doppler vibrometry (LDV).

Methods: We examined three fresh-frozen temporal bones (TB), two donated by white males and one by a Black female, using dynamic synchrotron-based X-ray microtomography for 256 and 512 Hz, stimulated at 110 dB and 120 dB sound pressure level (SPL). In addition, we performed measurements on these TBs using 1D LDV, a well-established method.

Results: The normalized displacement values (µm/Pa) at the umbo and the posterior crus of the stapes are consistent or within 5-10 dB differences between all LDV and dynamic microtomography measurements and previously reported literature references. In general, the overall behavior is similar between the two measurement techniques.

Conclusion: In conclusion, our results demonstrate the suitability of dynamic synchrotron-based X-ray microtomography in studying the middle ear's biomechanics. However, this study shows that better standardization regarding acoustic stimulation and measurement points is needed to better compare the two measurement techniques.

Purpose: Recent measurements show organ-of-Corti (OoC) motions that do not fit the classic hypothesis that outer hair cells (OHCs) amplify by pushing on the basilar membrane (BM) through stiff Deiters cells. One particularly surprising motion is that far below the best frequency (BF), the transverse motion of the OHC bottom is much greater than BM or reticular lamina (RL) motions.

Methods: We explore this with (1) data from seven gerbils showing that the ratio, Rohc, of transverse motions at the OHC top to the OHC bottom is small at low frequencies but large near BF and (2) a heuristic model for the impedances of structures in a transverse cut through the OoC (the TOoC model) that accounts for Rohc.

Results: The key idea is that when OHCs cyclically squeeze/expand, they force fluid out/into the space surrounding the OHCs which changes the local OoC area. At each time instant, cortilymph flows longitudinally along the tunnels from where OHCs squeeze to where OHCs expand, which is one-half the traveling-wave wavelength, λ. The impedance seen by OHCs for forcing cortilymph out/into and along the tunnels is termed Z_OUT. Assuming that Z_OUT decreases as λ gets shorter, the model Rohc shows the same frequency pattern as Rohc measurements.

Conclusion: Cyclic OHC forces produce OoC area changes consistent with those hypothesized to drive traveling-wave amplification. Z_OUT variation with λ allows wide-band OHC motility to produce large OoC area changes and RL motions only near BF where λ is small, thereby producing narrow-band traveling-wave amplification. The model accounts for why, at low frequencies, the motion at the bottom of the OHCs is larger than BM motion. The model also explains why the OoC has longitudinal fluid spaces that connect to the fluid surrounding the OHCs.

Quasiperiodic fluctuations with frequency are observed in a variety of responses that either originate from or strongly depend on the cochlea's active mechanics. These spectral microstructures are unique and stable features of individual ears and have been most thoroughly studied in behavioral hearing thresholds and otoacoustic emissions (OAEs). While the exact morphology of the microstructure patterns may differ across measurement types, the patterns are interrelated and are thought to depend on common mechanisms. This review summarizes the characteristics and proposed origins of the microstructures observed in behavioral and OAE responses, as well as other mechanical and electrophysiological responses of the mammalian cochlea. Throughout, the work of Glenis Long and colleagues is highlighted. Long contributed greatly to our understanding of microstructure and its perceptual consequences, as well as to the development of techniques for reducing the impact of microstructure on OAE-based assays of cochlear function.