JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY

Enhanced 40 and 80 Hz Auditory Steady State Responses in Patients with Idiopathic Tinnitus
Ghasemahmad Z, Mahmoudian S, Gavazzi D, Jalaei S and Farahani S
This study aimed to investigate changes in auditory processing using auditory steady state responses (ASSR) in patients with idiopathic tinnitus.
Latencies of Pulsed Distortion-Product Otoacoustic Emissions and Their Relation to Auditory Brainstem Responses
Dalhoff E, Zelle D and Bader K
To assess system properties of the human auditory system, such as cochlear gain, frequency selectivity, and their dependence on frequency and level, it is essential to examine the interrelation of various readouts. By measuring and analyzing otoacoustic emission (OAE) and auditory brainstem response (ABR) latencies, among others, predictions of cochlear models and applicability of properties such as the minimum-phase principle, level dependence of latencies, or related changes of the gain of a presumed positive-feedback mechanism can be investigated.
Suppression of Low-Frequency Tones in the Organ of Corti Vibrations of the Basal Turn in the Mongolian Gerbil Cochlea
Siegel JH, He W and Ren T
The basilar membrane (BM) motion evoked by single or two-tone stimuli shows nonlinearity largely confined to the region of the traveling wave peak(s) with a passive and linear response basal to the peak. For the same stimuli, nonlinear two-tone interactions in the ear canal pressure and cochlear microphonics appear to originate in a region that extends considerably basal to the peak of the BM traveling wave. Recent measurements from the reticular lamina region (RL) of the organ of Corti in the mouse apex exhibit active gain and broadly tuned two-tone suppression of the response to a lower-frequency probe stimulus that is not measured in the BM at the same location. These results suggest that suppressible active gain is evident in the RL region motion in the region basal to the characteristic frequency (CF) place of the probe tone. The purpose of this study is to explore the spatial extent of active gain and nonlinearity of the cochlear partition by measuring two-tone suppression in the RL region and BM responses to a probe two octaves lower in frequency than the CF of the recording location.
Longitudinal Vibrations in the Organ of Corti are Limited to Its Core
Meenderink SWF, van der Heijden M and Dong W
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.
Clinical Norms for Evaluating Hearing Difficulty in Patients with "Normal" Hearing Thresholds
Ellis GM, Davidson A and Brungart DS
The Effects of Broadband Elicitor Duration on Transient-Evoked Otoacoustic Emissions and a Psychoacoustic Measure of Gain Reduction
Salloom WB, Bharadwaj H and Strickland EA
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).
On the Sharpness of Auditory Filters: Considering Subclinical Deficits Reveals Sharper Otoacoustic Emission Estimates of Frequency Selectivity in Humans
Aryal S and Mishra SK
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.
Inhibition of Cortical Evoked Responses to Sound Pulses by Preceding Silent Gaps
Shabestari PS, Edvall NK, Vinding MC, Vanneste S, Lundqvist D, Neff P and Cederroth CR
The basic principle of sensorimotor gating (SMG) relies on the ability of a weak lead stimulus (such as a pre-pulse) to inhibit a startling effect of a following, more intense, abrupt stimulus-the so-called pre-pulse inhibition (PPI) paradigm. PPI has been used for near half a century as a means to investigate psychiatric disorders in which its disruption is a surrogate for altered SMG in schizophrenia. However, the blinking response is very variable, making it a poor outcome measure at the individual level. Unlike PPI, which is regulated in the lateral globus pallidus from the basal ganglia, inhibition of the startle reflex by preceding silent gaps embedded in continuous background noise is processed in the auditory cortex, making it particularly suitable for measuring cortical responses.
Chronic Auditory-Nerve Implant Enhances Brainstem Phase Locking to Electric Pulse Trains
Middlebrooks JC, Richardson ML, Carlyon RP and Lin HW
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.
An Integrated System for Comprehensive Mouse Peripheral Vestibular Function Evaluation Based on Vestibulo-ocular Reflex
Zhao T, Xiao S, Liu W, Zhong J, Sun B and Chen F
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.
Differential Chromatin Accessibility, Gene Expression, and mRNA Splicing Between Developing Cochlear Inner and Outer Hair Cells
Foo CZ, Duggan A, Bartom ET, Tao L and García-Añoveros J
The mammalian cochlea has two types of low abundance and highly specialized inner (IHC) and outer (OHC) mechanosensory hair cells. Their malfunction or death is a common cause of congenital and acquired deafness. IHCs and OHCs exhibit different transcriptomes during development. We wondered how differences in gene expression are regulated at the chromatin level in developing IHCs and OHCs, and whether there were also differences in mRNA splicing between IHCs and OHCs.
Magnetic Targeting of AAV Gene Therapy for Inner Ear Following Systemic Delivery: Preliminary Findings and Transduction Pattern in Rat Cochlea
Ferdous Z, Le TN, Zhang Z and Situ Y
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).
A Systematic Review on the Role of the Stria Vascularis in Menière's Disease Pathogenesis
Cruz-Granados P, Das S, Bagheri-Loftabad K and Lopez-Escamez JA
The stria vascularis (SV) is a secretory epithelium that maintains fluid homeostasis and generates the endocochlear potential in the cochlear duct. Multiomic studies have identified genes in the SV that could contribute to the pathogenesis of Menière's Disease (MD), a disorder defined by episodic vertigo, sensorineural hearing loss, and tinnitus. This systematic review identified genes expressed in the SV cell types (marginal, intermediate, and basal) and gap junction proteins to evaluate their pathophysiological connections to MD.
Comparison of Inner Ear Volume Between Humans and Sheep Using MRI
Micaletti F, Simier V, Fouan D, Cottier JP, Galvin JJ, Escoffre JM and Bakhos D
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.
Insights Into Stria Vascular Function, Stria Immunity, and Age-Related Hearing Loss
Shi X
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.
A Phenome-Wide Comorbidity Atlas of Age-Related Hearing Loss, Speech-in-Noise Deficits, and Tinnitus: Distinguishing Causal Signals from Correlation
Bhatt IS, Tucker D, Britton M, Hoffa A, Pate BJ, Dias R and Garay JAR
The present study employed a data-driven and hypothesis-free approach to identify comorbidities associated with age-related hearing loss (ARHL), speech-in-noise (SIN) deficits, and tinnitus.
Brief Acoustic Tinnitus Suppression as a Diagnostic Procedure in Clinical Routine: Feasibility and Results
Schoisswohl S, Vizethum M, Schecklmann M, Reissmann A, Vielsmeier V, Kerkel K and Langguth B
Brief acoustic tinnitus suppression (BATS) is a well-known phenomenon among tinnitus patients. Most knowledge about BATS comes from experiments applying filtered, modulated, or customized stimuli in selected patient populations. Testing BATS in clinical routine could provide valuable information for patient subtyping and assistance in treatment decision-making. Here, we investigated the feasibility of BATS tests beyond controlled experimental settings. Seventy individuals with tinnitus (29 female) were tested for BATS using white noise as part of a first consultation visit at the Interdisciplinary Tinnitus Center in Regensburg. The procedure turned out to be feasible under clinical routine conditions. Thirty-five patients (50%) reported some form of tinnitus suppression, with 6 (8.6%) reporting at least 50% reduction and 1 (1.4%) complete absence of their tinnitus percept. The degree of suppression was rated as relevant improvement by most patients. In summary, the integration of BATS assessments was feasible and provided valuable information about the patients' tinnitus.
Management Strategies for Chronic Suppurative Otitis Media and Why They Fail
Hura N, Xia A and Santa Maria PL
Chronic suppurative otitis media (CSOM) affects up to 330 million people globally and is one of the leading causes of pediatric hearing loss. Defined by a state of chronic infection in the middle ear in the setting of a tympanic membrane perforation, CSOM is traditionally most frequently associated with infection with Pseudomonas and Staphylococcus aureus species. The current therapeutic options for CSOM include medical therapy in the form of topical antibiotics or antiseptics (i.e., boric acid, acetic acid, povo-iodine), as well as surgical intervention with tympanoplasty or tympanomastoidectomy in refractory cases. While topical fluoroquinolones have the strongest level of evidence supporting their use for CSOM treatment, they are frequently associated with long-term treatment failure. Treatment failure is secondary to the presence of persister cells in CSOM, which are antibiotic tolerant and have the potential to proliferate and gain additional antibiotic resistance. As biofilms and persister cells are not routinely tested for in clinical medicine, there is limited data on therapeutic options that may eradicate biofilms and persister cells while limiting ototoxic effects. While future research should aim to identify such ototopical treatment options, clinicians may also consider surgical intervention earlier in patients with disease refractory to topical treatment to both minimize the risk of encouraging antibiotic resistance and to maximize the ability to debride the biofilm.
Reduced Cochlear Implant Performance in Listeners with Single-Sided Deafness: Comparison with Bilateral Listeners
Jeppsen C and McMurray B
The efficacy of the Cochlear Implant (CI) in listeners with single-sided deafness (SSD) was evaluated by comparing single-ear speech perception in SSD listeners and bilateral cochlear implant listeners (BCI).
How the Human Cochlea Moves: Biomechanical Modeling of a Wide, Layered Osseous Spiral Lamina
Tubelli AA, Secchia PA, Raufer S, Nakajima HH and Puria S
The human cochlear partition (CP) at the high-frequency region features a radially wide, layered osseous spiral lamina (OSL) and a soft-tissue bridge connecting it to the basilar membrane (BM). The OSL consists of two thin bony plates separated by a cavernous space that serves as a conduit for auditory nerve fibers. We used a finite element model with two fluid chambers, incorporating novel implementations of the CP features, to study the human cochlea. Model results were compared with experimental measurements of CP motion.
Analysis of miRNAs from Inner Ear Organoid-Derived Extracellular Vesicles
Lee S, Kubota M, Park E, Heller S, Im GJ and Chang J
Permanent hearing loss primarily results from the inability of the mammalian cochlea to replace lost inner ear hair cells. However, neonatal mice exhibit a unique capacity: isolated cochlear floor cells can efficiently proliferate in vitro and form organoids that harbor new hair cells and supporting cell populations. In this study, we isolated extracellular vesicles (EVs) from organoids and analyzed the miRNAs derived from them to identify gene regulatory elements that coordinate proliferation and regeneration.