In this thesis, I construct and evaluate biophysically realistic mathematical models of potassium transport in two inner ear epithelia. Deficits in potassium transport cause deafness and imbalance, because proper hearing and balance require the presence of an electrochemical potassium gradient. The first tissue considered is the cochlear stria vascularis, which produces the high endolymphatic potassium and endocochlear potential (EP). The prevailing theory for the operation of this epithelium is that one layer of cells provides a large current, which creates a low intrastrial potassium concentration that allows the EP to develop across the membranes of a second layer. The second tissue is the vestibular sensory epithelium, in which local ion accumulation in calyx-type synapses has been proposed to enhance synaptic signaling. I use computational models to study the behavior of both systems. For the stria vascularis, I applied compartmental analysis with the addition of equations for volume and electrical potentials. For the calyx synapse, I derive a distributed circuit model with Nernst-Planck electrodiffusion of potassium and a stochastic description of quantal transmission. Both models are based upon experimentally derived channel and transporter kinetics. The model of the stria vascularis accurately reproduces experimental measurements and confirms that the two-layer theory of EP generation is feasible with known channels and transporters. I can also estimate the potassium in the intrastrial space, which has not been accurately measured. Using the calyx model, I demonstrate nonquantal transmission in spite of high transporter densities, primarily by potassium accumulation and in a small part by ephaptic transmission. In addition to a direct effect on the afferent neuron, potassium increases the effective input resistance of the model hair cell, increasing quantal release. The model also exhibits retrograde transmission of afferent action potentials, which may be an observable measure of ephaptic transmission. These models provide information about variables that cannot easily be measured, such as the intrastrial and calyceal cleft potassium concentrations. Over time this work could grow into a complete multiscale model of inner ear ion transport, allowing virtual experiments of loss of function and restorative therapies.

Otitis media with effusion (OME) is a chronic inflammatory disease of the middle ear space characterized by the accumulation of fluid. Previous investigations have found the composition of the inflammatory substrate in effusions of allergy-associated otitis media to be is similar to the late-phase allergic response seen elsewhere in the respiratory tract, such as in asthma and in allergic rhinitis. In addition, there is evidence suggesting that diseases of the upper and lower airways may represent different clinical manifestations of a single inflammatory airway syndrome, or the United Airway Concept. The objective of this research is to determine if the middle ear compartment may be a component of the United Airways in allergic disease. Middle ear fluid, torus tubaris (Eustachian tube mucosa at the nasopharyngeal orifice) and adenoidal tissue biopsies were obtained from 45 patients undergoing simultaneous tympanostomy tube placement for OME and adenoidectomy for adenoid hypertrophy. The cellular and cytokine profiles of each site were investigated using immunocytochemistry (elastase, CD3, MBP) and in-situ hybridization (IL-4, IL-5, IFN-gamma mRNA). Atopic status was determined for each patient using skin-prick testing. Eleven of the 45 patients with OME (24%) were atopic. The MEE of atopics had significantly higher levels of eosinophils, T lymphocytes, IL-4 and IL-5 mRNA +cells (p < 0.01), and significantly lower levels of neutrophils and IFN-gamma mRNA +cells (p < 0.01) when compared to non-atopics. The nasopharyngeal tissue biopsies also revealed similar cellular and cytokine profiles. Therefore, the allergic inflammation in atopic patients with OME occurs on both sides of the Eustachian tube, both in the middle ear and in the nasopharynx. The results of this study support the concept that the middle ear may be part of the United Airway in atopic individuals.

Background. Otitis media with effusion (OME) is more common in atopic children. Few studies have looked for the presence of inflammatory mediators in the middle ear effusions of this population. / Objectives. We hypothesize that atopic children with OME have a different inflammatory cell and cytokine profile than non-atopic children with the disease. / Methods. The atopic status of 26 children with OME was determined. Using immunocytochemistry, fluid specimens were assessed for T lymphocytes, eosinophils, neutrophils, mast cells, and basophils. The expression of IL-4, II.-5, and IFN-gamma mRNA was assessed using in-situ hybridization. / Results. There is a higher percentage of eosinophils, T lymphocytes and cells expressing IL-4 and IL-5 mRNA in atopic children (n = 8) compared to non-atopic controls (n = 18) (p < 0.01). / Conclusion. The predominance of eosinophils, T lymphocytes and Th2 mediators in the middle ear effusions of atopic children provides strong evidence that atopy plays a role in the pathogenesis of this condition.

A finite-element model of the cat middle ear was modified to include a shell representation of the incudostapedial joint. A low-frequency, uniform sound pressure was applied to the eardrum. Joint stiffness was varied from very low to very high. The resulting displacements of the stapedial footplate, incudostapedial joint, manubrium and eardrum were examined. The footplate tilts both anteroposteriorly and inferosuperiorly for almost all Young's modulus values. The in-plane rotation of the footplate is greatest when the incudostapedial joint is effectively rigid. The joint compresses most when it is extremely flexible and less as the joint becomes less flexible. The joint compression is greater than the joint shear. The displacement pattern of the eardrum is relatively insensitive to changes in the joint stiffness.

The middle ear is a small air-filled cavity which contains a chain of three small bones or ossicles: the malleus, the incus and the stapes. There is a tiny bony bridge (pedicle) between the long process of the incus and the lenticular process, but little or nothing is known about the effect of the pedicle on the movements of the ossicles. The motivation of the work presented here is to improve our understanding of the mechanical behaviour at the pedicle and the incudostapedial joint, in particular the relative contributions of the two structures to sound transmission through the middle ear. / A three-dimensional finite-element model of the pedicle and the incudostapedial joint was created, where the dimensions are based on examination of histological sections of a cat middle ear. Careful attention has been paid to the mesh generation of the model, especially for the regions of interest, such as the pedicle, that are very small relative to the overall structure. The issue of the compromise between the mesh resolution and the computational time will be discussed as well. Ranges of plausible values for the stiffnesses of the joint, joint capsule and pedicle were tested and the resulting displacements were examined for various loading conditions.

<p> Hearing loss and cognitive impairment are significant health problems, threatening the independent function of older adults. While there appears to be a strong relationship between the two conditions, the mechanisms underlying this association are complex and are not fully elucidated.</p><p> The purpose of this secondary analysis was to explore the relationship between hearing ability and cognitive performance in older adults. In addition, this study attempted to examine the role of depressive symptoms in the relationship between hearing loss and cognitive performance. Comprehensive measures of peripheral hearing, central auditory processing and cognitive performance were utilized to examine these relationships in a sample (N = 30) of adults aged 60 years and older. The Geriatric Depression Scale (GDS) was used to assess depressive symptoms.</p><p> Correlational analyses revealed a statistically significant relationship between central auditory processing and executive function. Statistically significant relationships were also observed between speed of processing and peripheral hearing as well as central auditory processing. No significant relationships were noted between depressive symptoms, hearing acuity and cognitive performance. While the correlation coefficients <i>(r)</i> for several of the hearing and cognitive performance measures were not statistically significant, medium effect sizes were detected, suggesting a moderate association may exist between these variables.</p>

Thesis (Ph.D.)--Pacific Graduate School of Psychology, 1991. / Source: Dissertation Abstracts International, Volume: 65-10, Section: B, page: 5439.

This work investigates auditory speech processing through measurement of brainstem responses to the synthetic vowel /a/, and variants containing the first formant (F1) only or the second and third formants only, in quiet and in white background noise. The results show that the response at the fundamental frequency (F0) is more robust to noise than the response at F1. This study also provides an insight into the potential locations where the pitch of resolved and unresolved harmonics is extracted in the auditory system, and how the frequency regions dominated by resolved/unresolved harmonics contribute to the response at F0. Based on the results, a conceptual model of the neural processing underlying the generation of the electrophysiological response at F0 is proposed.

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