Purpose: Frequency selectivity plays a crucial role in auditory perception, yet its precise characterization in humans remains debated. Most behavioral or physiologic estimates of frequency selectivity in humans have historically been obtained from individuals with clinically normal audiograms. However, emerging evidence suggests that even within this population, subclinical cochlear deficits may be prevalent, potentially skewing prior tuning estimates toward broader bandwidths. Here, we tested the hypothesis that human cochlear tuning is sharper when subclinical deficits, specifically hearing sensitivity above 8000 Hz, are considered.
Methods: Using stimulus frequency otoacoustic emission (SFOAE) delays, we obtained physiological estimates of cochlear tuning sharpness (QERB). We applied the Stockwell transform, optimized through in silico experiments, to accurately extract SFOAE delays in adults with normal audiograms (n = 37) while systematically accounting for hearing thresholds above 8000 Hz.
Results: Our findings demonstrate that controlling for subclinical deficits results in significantly sharper (higher) tuning estimates at 2000 and 2828 Hz among the tested frequencies. Additionally, applying a normative criterion for extended high-frequency hearing, we observed narrower equivalent rectangular bandwidths-approximately two times sharper-in individuals with better extended high-frequency sensitivity. The QERB estimates aligned closely with forward masking data in the literature, reinforcing the view that humans possess sharper cochlear tuning than common laboratory animals.
Conclusion: These findings highlight the influence of subclinical hearing deficits on cochlear tuning estimates and suggest that humans with optimal cochlear health may possess even sharper biological frequency selectivity than previously reported.
Purpose: This study aimed to investigate changes in auditory processing using auditory steady state responses (ASSR) in patients with idiopathic tinnitus.
Methods: 19 tinnitus patients (7 females) and 24 control subjects (9 females) without tinnitus were examined with multiple ASSRs. Three modulation frequencies of 20, 40, and 80 HZ were tested, and the steady state responses were compared between tinnitus and control group. Further, the thresholds in ipsi- and contralateral side to ear with tinnitus were compared.
Results: Our findings showed no significant difference in ASSR thresholds in ipsi- and contralateral side in tinnitus patients. However, we observed enhanced ASSRs at 40 and 80 Hz modulations in patients with idiopathic tinnitus compared to no-tinnitus control subjects.
Conclusion: The results of this study suggest possible sensory deficits along higher order auditory regions in patients with idiopathic tinnitus. Further, our data indicates a bilateral involvement of auditory pathway in these regions in patients with lateralized tinnitus.
The microvasculature plays a crucial role in maintaining auditory health by delivering essential nutrients such as glucose, ions, growth factors, and hormones, while also facilitating the elimination of metabolic waste. Simultaneously, the innate immune system acts as a protective barrier against cochlear damage caused by infections, toxic substances, and foreign agents. The normal functioning of these two systems creates an appropriate microenvironment that supports the health of sensory hair cells and spiral ganglion neurons. Disruptions in blood flow or inappropriate activation of the immune response can result in cochlear hypoxia and inflammation, both of which are linked to various auditory disorders. Understanding the characteristics and functions of these two systems could offer valuable insights into their distinct roles, potentially leading to the development of new treatments for hearing disorders associated with their dysfunction. This review covers the cellular characteristics and functions of both the vascular network and the innate immune cells within the stria vascularis, with a particular focus on how changes in both systems contribute to age-related hearing loss (ARHL), a common sensory deficit affecting the elderly population.
Purpose: Measures of the human medial olivocochlear reflex (MOCR) typically rely on long duration (> 100 ms) or continuously presented broadband elicitors. MOCR gain reduction measured by otoacoustic emissions (OAE) exhibits multiple time constants, including in the hundreds of milliseconds, when elicited by broadband noise. Psychoacoustic studies of gain reduction have largely adopted these elicitor characteristics, but less is known about how broadband elicitor duration affects auditory perception. Additionally, the literature on the relationship between psychoacoustic and OAE measures of gain reduction has yielded mixed results, which is counterintuitive if both measures reflect the same mechanism. In this study, the effects of ipsilateral broadband elicitor duration were evaluated using forward masking psychoacoustic and transient-evoked OAE (TEOAE) paradigms in individuals with normal hearing (N = 19; m = 7, f = 12).
Methods: Ipsilateral pink broadband noise was used as the elicitor in both experiments, presented at 50 dB SPL (50-800 ms) for the psychoacoustic measures and 50 dB FPL (50-400 ms) for the TEOAE measures. Gain reduction was quantified as the change in signal threshold (2 kHz) and the change in TEOAE level (1/3rd-octave band centered at 2 kHz) with and without the presence of the elicitor.
Results: The average time constants for psychoacoustic and TEOAE gain reduction were similarly short (< 100 ms), with near-maximal effects observed for elicitor durations of 200 ms. However, individual comparisons of TEOAE and psychoacoustic gain reduction revealed mixed results. Potential factors contributing to this discrepancy are discussed.
Conclusion: The human MOCR reduces cochlear gain on relatively short time scales (< 100 ms) with ipsilateral broadband elicitors.
Purpose: The goal of this research was to determine where in the organ of Corti (ooC) sound-induced, longitudinal vibrations occur, and how they depend on the health of the cochlea.
Methods: Sound-evoked vibrations of the ooC in the cochlea's middle turn of adult anesthetized gerbils were measured using optical coherence tomography (OCT). Vibratory responses, evoked with acoustic tone complexes, were recorded at multiple, closely spaced (20 μm), tonotopic locations which changed the "viewing angle" of the vertical OCT beam re. the longitudinal motion. After spatial alignment of the responses, within-ooC regions exhibiting sound-induced longitudinal motion were identified from a conspicuous 180° phase flip.
Results: Longitudinal motion was restricted to the outer hair cells (OHC), Deiters' cells and the tunnel of Corti (i.e., the ooC's "core"). They were frequency and level-independent but did depend on the ear's metabolic state; after death, they disappeared.
Conclusion: There can be little doubt about the presence of longitudinal motions within the cochlea. Their disappearance postmortem and spatially restricted occurrence suggest these longitudinal vibrations arise from active processes within the OHC. Whether this involves cycle-by-cycle feedback or some other, as-of-yet undetermined, mechanism remains to be resolved.
Purpose: Delivery of therapeutics to the inner ear is complicated by their inaccessible location and the presence of the blood-labyrinth barrier that restricts most blood-borne compounds from entering the inner ear. This study addresses the challenge of optimal delivery in treating inner ear disease, focusing on magnetic targeting gene therapy using adeno-associated virus (AAV).
Methods: The investigation explores three AAV serotypes (AAV2 Quad Mut, AAV2 pANC80L65, and AAV9 PHP.eB) delivered systemically, tagged with a brain-derived nerve growth factor (BDNF) transgene and GFP reporter protein, and captured with superparamagnetic nanoparticles. External magnets target AAV delivery to the Left ear of both male and female Long Evans rats. After 2 weeks, we evaluated tropism and transduction in both cochleae and assessed distribution in other major organs (heart, lung, liver, kidney, spleen, and brain) using immunohistochemistry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assays. Six animals were used for each experimental group.
Results: Immunofluorescence analysis demonstrated the qualitative distribution of AAVs in sensory cells and spiral ganglion neurons (SGN) in both ears. A significant increase in BDNF gene expression in the targeted left ear of rats administered AAV2 Quad Mut was observed. A single dose of magnetic targeting of AAV2 Quad Mut effectively transduced SGN and enhanced BDNF expression, leading to the restoration of ouabain-induced SGN loss and hearing loss (HL).
Conclusion: These findings indicate the potential of magnetic targeting to direct gene therapy following systemic delivery, paving the way for future applications in the treatment of HL.
Purpose: In preclinical research, animals are used to perform clinical experiments. The use of large animals with human-like anatomies and structural size appears to be essential. For auditory function research, we needed to identify an animal model whose dimensions are close to those of the human inner ear for future research. In the present study, we investigated measurements of the human and sheep inner ear using 3 T Magnetic Resonance Imaging (MRI) to evaluate the suitability of a sheep model for studying the inner ear.
Methods: Inner ears were compared between 8 ears from 4 normal humans (women) and 8 ears from 4 normal sheep (female). Cranial MRI of both species' cochleae were acquired and analyzed, with specific measurements for key anatomical features, including the cochlea length and width, the length and width of the inner auditory canal, the number of spiral turns of the cochlea and the cochlea volume. The size ratios between sheep and human cochlear structures were calculated and compared.
Results: Overall cochlear dimensions of the sheep were approximately 2/3 that of human cochleae across most measurements, except for the internal auditory canal. The internal auditory canal of the sheep was 1/3 of the size of that in humans. The number of spiral turns in the cochlea was equivalent between the two species.
Conclusion: Given the proportionally similar dimensions to humans, the sheep cochlea appears to be a promising model for inner ear research, specifically to develop pathological models, to study the pathophysiological mechanisms of inner ear diseases, and/or to improve treatment with implantable prostheses.
Purpose: Present-day cochlear implants (CIs) can deliver usable speech reception in quiet surroundings. Most CI users, however, show impaired sensitivity to temporal fine structure, which hampers their use of pitch contours and spatial cues to segregate competing talkers. In previous short-term animal studies, we used intraneural (IN) electrodes to stimulate pathways originating from various cochlear turns. Neurons in the inferior colliculus synchronized to apical stimulation at higher rates than to stimulation of the middle-to-basal pathways that are stimulated primarily by today's CIs. Here, we use non-invasive recordings to test the safety and efficacy of up to 6 months of IN implantation and stimulation in cats.
Methods: Deafened cats (ten female, two male) were implanted with IN and/or conventional CI electrodes. The IN electrodes were single activated-iridium shanks that targeted apical-turn fibers. Scalp recordings were made from sedated animals at 2-3-week intervals. Auditory brainstem responses to single electrical pulses (eABR) tracked sensitivity and growth of responses. Frequency following responses to electrical pulse trains (eFFR) assessed brainstem temporal transmission at varying pulse rates.
Results: Thresholds for eABR were lower for IN than for CI stimulation, dynamic ranges were wider, and (by inference) spread of activation was more restricted. The eFFR evaluated at latencies comparable to those of inferior-colliculus spikes synchronized at maximum pulse rates averaging > 360 pulses/s for IN compared to ~ 240 pulses/s for CI stimulation. The eABR thresholds and eFFR cutoff rates were stable out to 6 months after implantation.
Conclusions: The results demonstrate the safety and efficacy of chronic IN stimulation in an animal model. In a future clinical device, an IN electrode could augment cochlear-implant performance by enhancing temporal acuity, thereby improving speech reception amid competing sounds.
Purpose: In the fields of both vestibular and auditory research, reliable vestibular function tests are essential. However, unlike the auditory function tests, which use standard Auditory Brainstem Response (ABR) equipment, there is no equivalent widely adopted apparatus for vestibular tests. Vestibulo-ocular reflexes (VORs) are the compensatory ocular reflexes that ensure stable vision during head motion. VORs are widely used in clinics to diagnose vestibular deficits. In the research, VORs have been used by various groups to evaluate the mouse vestibular function. However, the effectiveness of VOR tests has not been systematically evaluated with appropriate mouse models, and the lack of commercial equipment hampers its accessibility, confining vestibular testing to a select few labs.
Methods: In this study, we developed an integrated and surgery-free instrument system with both angular VOR (aVOR) and off-vertical axis rotation (OVAR) modes for evaluating mouse vestibular function. In addition, the eye rotation calibrations used in this study standardize the data between instruments. To demonstrate its validity and efficacy of the testing equipment, we evaluated four mouse models, including both genders, with peripheral vestibular deficits: 1) mice injected with the vestibulotoxic drug 3,3'-iminodiproprionitrile (IDPN, 2 mg/g and 4 mg/g, 3 male/3 female per group); 2) Critical MET-related mutant mice (Cdh23v2J/v2J, 4 male/4 female and TMC1-/-, 6 male/5 female); 3) Vestibular-specific mutant mice (Zpld1-/-, 6 male/6 female, for semicircular canal dysfunction and Otop1tlt/tlt, 3 male/2 female, for otoconia deficient); 4) Unilateral vestibular lesion (UVL) mouse model (3 male/3 female per group) where gentamicin was injected into horizontal semicircular canal.
Results: The results showed: 1) Quantification of vestibular deficits can be achieved as a daily routine; 2) Both the horizontal semicircular canal and otolith organs can be assessed, respectively; and 3) The lesion side of UVL can be identified.
Conclusion: These test results reveal the potential of our system as standard equipment for evaluating common vestibular deficits in mice.
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