Hearing Health

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Matthew Masapollo, Ph.D.

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Matthew Masapollo, Ph.D.

University of Florida
Contributions of auditory and somatosensory feedback to speech motor control in congenitally deaf 9- to-10-year-olds and adults

Cochlear implants have led to stunning advances in prospects for children with congenital hearing loss to acquire spoken language in a typical manner, but problems persist. In particular, children with CIs show much larger deficits in acquiring sensitivity to the individual speech sounds of language (phonological structure) than in acquiring vocabulary and syntax. This project will test the hypothesis that the acquisition of detailed phonological representations would be facilitated by a stronger emphasis on the speech motor control associated with producing those representations. This approach is novel because most interventions for children with CIs focus strongly on listening to spoken language, which may be overlooking the importance of practice in producing language, an idea we will examine. To achieve that objective, we will observe speech motor control directly in speakers with congenital hearing loss and CIs, with and without sensory feedback.

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Jameson Mattingly, M.D.

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Jameson Mattingly, M.D.

The Ohio State University
Differentiating Ménière's disease and vestibular migraine using audiometry and vestibular threshold measurements

Patients presenting with recurrent episodic vertigo (dizziness), such as Ménière's disease (MD) and vestibular migraine (VM), can present a diagnostic challenge as they can both produce recurrent vertigo, tinnitus, motion intolerance, and hearing loss. Further complicating this issue is that the diagnosis of each is based upon patient history with little contribution from an objective measure. Previous attempts to better differentiate MD and VM have included a variety of auditory and vestibular tests, but these evaluations have demonstrated limitations or not shown the appropriate sensitivity and specificity to be used in the clinical setting. Recently, vestibular perceptual threshold testing has shown the potential to better differentiate MD and VM by demonstrating different and opposite trends with testing, and these evaluations are ongoing. In addition to vestibular evaluations, audiometry (hearing testing) is a mainstay of testing in those with vestibular symptoms, especially with any concern of MD, and is thus commonly available. Standard hearing testing, however, is not sensitive or specific enough alone to differentiate MD and VM, but this project’s hypothesis is that combining audiograms with vestibular perceptual threshold testing will result in a diagnostic power greater than that possible with either option used individually. The population of patients with MD and VM is an ideal setting to examine similarities and differences, as MD is classically an otologic disease and VM, in theory, has little to do with auditory function. Additionally, this same principal can be applied to any disease process that affects both vestibular and auditory function (such as tumors, ototoxicity).

Andrew A. McCall, M.D.

Andrew A. McCall, M.D.

University of Pittsburgh
The Influence of Dynamic Limb Movement on Activity within the Vestibular Nuclei: the Role of the Cerebellum

Balance is inherently a multi-modal sense. To maintain balance in upright stance or during walking, input from several modalities – namely the vestibular system (from the inner ear), proprioceptive system (from muscles and joints), and visual system – must be interpreted by the central nervous system and synthesized to understand body position in space relative to gravity. Our goal is to investigate how vestibular and limb proprioceptive inputs interact in the central nervous system, with a particular focus on the brainstem and cerebellum as these are key sites of multisensory processing of balance input. We anticipate that the results of these studies will have important implications for the understanding of multi-sensory processing within central vestibular pathways and for the clinical treatment of humans with vestibular disorders.

Research area: Vestibular and Balance Disorders; Vestibular Physiology

Long-term goal of research: To elucidate the physiologic pathways responsible for integrating vestibular and proprioceptive information and to ultimately develop clinical strategies based upon these physiologic underpinnings to improve the health of humans with vestibular disorders.

Melissa McGovern, Ph.D.

Melissa McGovern, Ph.D.

University of Pittsburgh

Hair cell regeneration in the mature cochlea: investigating new models to reprogram cochlear epithelial cells into hair cells 

Sensory hair cells in the inner ear detect mechanical auditory stimulation and convert it into a signal that the brain can interpret. Hair cells are susceptible to damage from loud noises and some medications. Our lab investigates the ability of nonsensory cells in our inner ears to be able to regenerate lost hair cells. We regenerate cells in the ear by converting nonsensory cells into sensory cells through genetic reprogramming. Key hair cell-inducing program genes are expressed in non-hair cells and partially convert them into hair cells. There are multiple types of nonsensory cells in the inner ear and they are all important for different reasons. In addition, they are in different locations relative to the sensory hair cells. In order to better understand the ability of different groups of cells to restore hearing, we need to be able to isolate different populations of cells. The funded project will allow us to create a new model to target specific nonsensory cells within the inner ear to better understand how these cells can be converted into hair cells. By using this new model, we can specifically investigate cells near the sensory hair cells and understand how they can be reprogrammed. Our lab is also very interested in how the partial loss of genes in the inner ear can affect cellular identities. In addition to targeting specific cells in the ear, we will investigate whether the partial loss of a protein in nonsensory cells may improve their ability to be converted into sensory cells. This information will allow us to further explore possible therapeutic targets for hearing restoration.

Kathleen McNerney, Ph.D.

Kathleen McNerney, Ph.D.

University at Buffalo, SUNY

The vestibular evoked myogenic potential: unanswered questions regarding stimulus and recording parameters

The vestibular evoked myogenic potential (VEMP) is a response that can be recorded from the sternocleidomastoid (SCM) muscle as well as other neck muscles such as the trapezius. It is believed to be generated by the saccule, which is a part of our vestibular system that is normally responsible for our sense of balance. Recent studies have shown that it is also responsive to sound. Three types of stimuli that are used to elicit the VEMP are air-conducted (AC) stimuli, bone-conducted (BC) stimuli, and galvanic (electrical) stimuli. Although there are several universal findings that have held true throughout previous studies, there are several questions which remain unanswered. The present study will attempt to address these issues by making a direct comparison between the three types of stimuli listed above, within the same subjects. In addition, input/output functions will be defined for all three types of stimuli. Finally, we will be looking at the repeatability of the three types of stimuli across subjects as well as address the inconsistencies that have been found between monaural and binaural stimulation. This study will not only provide us with a better understanding of the VEMP, it will also enhance its clinical utility.

Iain M. Miller, Ph.D.

Iain M. Miller, Ph.D.

Ohio University

The distribution of glutamate receptors in the turtle utricle: a confocal and electron microscope study

When stimulated by acceleration and head tilt (gravity), sensory hair cells in the turtle utricle, an organ in the inner ear, transmit information about these stimuli to the brain. The long term goal of this research is to understand what role synaptic structure and composition play in the observed spatially heterogeneous and diverse discharge properties of afferents supplying the vestibular end organs, and in particular, the utricle. This knowledge is central for accurate diagnosis and rational treatment strategies for vestibular dysfunction.

Jane Mondul, Au.D., Ph.D., CCC-A

Jane Mondul, Au.D., Ph.D., CCC-A

Purdue University

Sound-induced plasticity of the lateral olivocochlear efferent system

Loud sounds can damage the auditory system and cause hearing loss. But not all sound is bad – safe sound exposure can actually help the brain fine-tune how we hear, especially in noisy places. A part of the auditory system called the lateral olivocochlear (LOC) pathway may help with this. The LOC system’s chemical signals change after sound exposure, suggesting a form of “plasticity” (adaptability), but scientists don’t yet know exactly how it works. Our project will study how the LOC system changes after safe sound exposure, how this LOC plasticity affects hearing, and whether it still occurs when the ear is damaged. We will test this in mice by measuring their ability to hear sounds in noise and by looking closely at cells in the ear and brain. What we learn could guide new sound-based or drug-based therapies to protect hearing and improve communication in noisy settings.

Bruna Mussoi, Au.D., Ph.D.

Bruna Mussoi, Au.D., Ph.D.

University of Tennessee

Auditory neuroplasticity following experience with cochlear implants

Cochlear implants provide several benefits to older adults, though the amount of benefit varies across people. The greatest improvements in speech understanding abilities usually happen within the first 6 months after implantation. It is generally accepted that these gains in performance are a result of neural changes in the auditory system, but while there is strong evidence of neural changes following cochlear implantation in children, there is limited evidence in adults with hearing loss in both ears. This study will examine how neural responses change as a function of the amount of cochlear implant use, when compared to longstanding hearing aid use. Listeners who are candidates for a cochlear implant (who either decide to pursue implantation or to keep wearing hearing aids) will be tested at several time points, from pre-implantation and up to 6 months after implantation. The results of this project will improve our understanding of the impact of cochlear implant use on neural responses in older adults, and their relationship with the ability to understand speech.

Mirna Mustapha-Chaib, Ph.D.

Mirna Mustapha-Chaib, Ph.D.

University of Michigan

Determine the functional role of the unique amino terminus of MYO15 in hearing using genetically engineered mice

Assessing the role of the N-terminus of MYO15 in structural development of hair cells and in the neurosensory process of hearing is expected to provide basic information about the process of hearing at the molecular level. Long term, we expect proteins that interact with the N-terminus of MYO15 will also be defective in some forms of hearing loss. Models similar to the one we propose have been used as proof of principle for gene therapy. Mutations in humans indicate that the N-terminal portion of MYO15 is required in some way for hearing. Using our resources and experience in genetically engineered mice will advance the understanding of the specific molecular function of the N-terminus of Myo15 in mammalian hearing and determine the consequences on morphological development and signal transduction within the cochlear hair cells. Thus, these studies will immediately make a contribution to the rapidly advancing field of molecular hearing research. The next step will be to identify the proteins that interact with the N-terminus, screen pedigrees for mutations in these genes and work towards therapeutic intervention for genes that are common causes of deafness.

Gowri Nayak, Ph.D.

Gowri Nayak, Ph.D.

Cincinnati Children’s Hospital Medical Center
Signaling defects due to Tricellulin deficiency

Mutations in a protein called Tricellulin lead to hereditary hearing loss in humans and degeneration of cochlear sensory cells and deafness in mice. In the inner ear, Tricellulin is found in the sensory epithelia at sites where three epithelial cells meet. The localization of Tricellulin at the junction between cells gives it the potential to respond to external cues and transmit the signals to the cell interior. The current project aims at uncovering the potential cellular signaling roles of Tricellulin by determining the gene expression changes in the inner ear of Tricellulin mutant mice compared to wild-type mice. The results of this study will not only add to the existing knowledge of the inner ear development and maintenance but also will examine the direct effects of losing a protein that helps preserve our hearing.

Research area: Fundamental Auditory Research

Long-term goal of research: To determine the role of cell junction proteins in the inner ear function and elucidate the biological processes that are affected by genetic mutations in these proteins. As tight junctions are also the focus of drug delivery studies, it is valuable to realize the cellular functions of the associated proteins so that they can be manipulated for therapeutic purposes.

Kevin K. Ohlemiller, Ph.D.

Kevin K. Ohlemiller, Ph.D.

Washington University
Cellular and Genetic Bases of Age-Associated Strial Degeneration and EP decline in NOD congenic mice

The electric currents that run through cochlear sensory cells are largely driven by a specialized cochlear structure called the stria vascularis. The work of the stria requires a lot of energy, so that it is densely vascularized (hence the name). Loss of strial blood vessels is thought to be a common cause of age-related hearing loss. Not everyone shows signs of this kind of pathology, however, so that there must be forms of certain genes carried by some people that act as ‘risk’ genes. People who carry ‘risk’ genes may be more likely to experience loss of strial blood vessels, and ultimately loss of the stria itself. In 2008 we discovered that a particular breed of mice (NOD mice) start out with a normal stria, but then show loss of strial vessels, followed by loss of the stria beginning from both ends of the cochlea and progressing toward the middle. These changes were accompanied by other distinctive anatomic features that may tell us something about the process, or may be unrelated. By crossing these mice with another strain that does not show pathology, we will be able to determine what pathologic features are inherited together (thus caused by the same genes), how many genes are involved, and their approximate locations. Any gene(s) we find may have human counterparts that exert similar effects.

Research areas: auditory physiology/pathophysiology, cell biology of hearing and deafness

Long-term goal of research: Finding ‘risk’ genes may not point directly to cures or allow us to predict who will lose their hearing. Nevertheless, identifying the genes, gene networks, and gene products will help pinpoint key reactions that can be tweaked pharmacologically. We are among the first to seek out mouse strains with pathology of the stria vascularis and to use these to uncover genes that promote strial degeneration in mice, and possibly in humans.

Carolyn P. Ojano-Dirain, Ph.D.

Carolyn P. Ojano-Dirain, Ph.D.

University of Florida College of Medicine
Prevention of aminoglycoside-induced hearing loss with the mitochondria-targeted antioxidant MitoQ

Aminoglycoside antibiotics, such as gentamicin, are commonly used to treat serious infections due to bacteria. However, these drugs can cause hearing loss. At present, there is no solution to prevent hearing loss caused by aminoglycoside antibiotics. This research will determine if the antioxidant MitoQ will prevent hearing loss induced by aminoglycoside antibiotics.

Research area: Hearing loss, Ototoxicity

Long-term goal of research: To develop and apply practicable intervention strategies to prevent hearing loss induced by drugs that are toxic to the inner ear.

Christian N. Paxton, Ph.D.

Christian N. Paxton, Ph.D.

University of Utah

The role of Fgf4 in otic placode induction

Development and patterning of the inner ear is a complex process that is mediated by several signaling molecules, including members of the fibroblast growth factor (FGF) family. We recently found that Fgf4 is expressed in the ear-forming region just prior to the induction of ear development. Fgf4 has not previously been described in the induction or formation of the inner ear. Based on its temporal and spatial pattern of expression we hypothesize that Fgf4 is involved in the early processes of ear development and propose to investigate its role(s) in these processes by determining whether it is sufficient and/or required to induce the early stages of inner ear development. We also will examine the signals responsible for localizing Fgf4 expression to the otic forming domain.

Tatjana Piotrowski, Ph.D.

Tatjana Piotrowski, Ph.D.

University of Utah Medical School

Molecular analysis of hair cell regeneration in the zebrafish lateral line

We are aiming to elucidate the genetic pathways underlying hair cell regeneration in zebrafish with the long-term goal of activating these pathways in mammals. Our lab is taking a twofold approach to identify genes involved in hair cell regeneration. We are performing gene expression analyses from mantle cells of control larvae and from larvae in which mantle cells are proliferating to regenerate killed hair cells (as proposed in this application). As a second approach we are performing a mutagenesis screen for zebrafish mutants which are not able to regenerate hair cells, and thus carry mutations in regeneration-specific genes. A prominent cause of deafness is loss of hair cells due to age, noise or antibiotic treatments. In contrast to mammalian hair cells, fish, bird and amphibian hair cells turn over frequently and regenerate following hair cell death. Little is known why lower vertebrates are able to regenerate hair cells but humans do not. This is partly due to the relative inaccessibility of inner ear hair cells to direct observation and manipulation. Our aim is to take advantage of the lateral line of zebrafish to define and characterize the molecular and cellular interactions occurring during hair cell regeneration. If successful, our results will set the stage for testing whether hair cell regeneration can be activated in humans.

Sarah F. Poissant, Ph.D.

Sarah F. Poissant, Ph.D.

University of Massachusetts, Amherst
The Impact of Total Communication on the Auditory Perception of Speech

For decades, most children with severe-to-profound hearing loss were educated in special schools for the deaf. In more recent years, increasing numbers of these children have been partially or fully main-streamed and educated along-side their peers with normal hearing. Much debate has ensued regarding the best language of instruction (sign-only, sign+speech, speech only) for them. It is generally thought that a symbolic, gesture-based language system, such as manually-coded English used as part of simultaneous communication methods, provides a facilitative benefit. However, there is not enough information about how children combine manual and spoken cues in this type of communication system to draw firm conclusions about optimal approaches to classroom teaching that best support aural reception of spoken language. We plan to ask and answer a very specific question: What is the direct effect of simultaneously delivered sign language on the perception of speech for children with hearing loss developing spoken language? The research approach builds from the observation that perception of speech that has been artificially degraded (e.g., to mimic a hearing loss) is strikingly improved when listeners have knowledge of the content of the message. The proposed study applies this hypothesis to children with hearing loss to determine whether signs serve in part as a prime to improve auditory perception of speech.

Research area: Auditory Development; Congenital Hearing Loss; Fundamental Auditory Research

Long-term goal of research: To assess how total communication – the combined use of manual signs, speech, and speech-reading – can most effectively be employed as a habilitation strategy to improve auditory perceptual abilities.

Sonja Pyott, Ph.D.

Sonja Pyott, Ph.D.

University of North Carolina Wilmington

Enhancement of the efferent-hair cell synapse by metabotropic glutamate receptors

This proposal aims to improve our understanding of the molecular mechanisms regulating synapses in the cochlea and will specifically characterize how a class of molecules, metabotropic glutamate receptors (mGluRs), regulates the efferent-hair cell synapses. Sensory hair cells of the cochlea communicate with the brain at specialized sites called synapses. Inner hair cells have numerous afferent synapses that relay information about sound from the hair cell to the brain. In contrast, outer hair cells are characterized by efferent synapses from the brain that regulate hair cell activity. Although these efferent and afferent synapses are normally considered to be independent from one another, experiments studying immature inner hair cells suggest that glutamate, the neurotransmitter required for transmission at the afferent synapse, may also modify the response of the efferent synapse. Efferent innervation of the cochlea is thought to protect against noise-induced hearing loss. Considering that noise-induced hearing loss accounts for one-third of all cases of deafness, understanding the mechanisms regulating efferent synapses is of special clinical relevance. This project will investigate this hypothesis and should uncover novel pharmaceutical targets to modulate the efferent synaptic response to either dampen hair cell activity and prevent noise-induced hearing or boost hair cell activity and combat deafness.

Lavanya Rajagopalan, Ph.D.

Lavanya Rajagopalan, Ph.D.

Baylor College of Medicine

The structural and functional basis of electromotility in prestin, the outer ear amplifier protein

Prestin, a membrane protein in outer hair cells in the cochlea, is involved in cochlear amplification leading to frequency sensitivity. The long-term objectives of this study are to understand the molecular basis of prestin function, to advance the field closer to designing therapeutics in certain types of hearing loss. This will provide insight into the molecular basis of prestin-related hearing loss, and can lead to rational design of therapeutics to treat such conditions.

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Robert Raphael, Ph.D.

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Robert Raphael, Ph.D.

Rice University
Understanding the biophysics and protein biomarkers of Ménière’s disease via optical coherence tomography imaging

Our sense of hearing and balance depends on maintaining proper fluid balance in a specialized fluid in the inner ear called the endolymph. Ménière’s disease is an inner ear disorder associated with increased fluid pressure in the endolymph that involves dizziness, hearing loss, and tinnitus. Ménière’s disease is difficult to diagnose and treat clinically, which is a source of frustration for both physicians and patients. Part of the barrier to diagnosing and treating Ménière’s disease is the lack of imaging tools to study the inner ear and a poor understanding of the underlying causes. The goal of this research is to develop an approach to noninvasively image the inner ear and study the internal structures in the vestibular system in typical and disease states. We will utilize optical coherence tomography (OCT), a technique capable of imaging through bone, and observe changes in the fluid compartments in the inner ear. The expected outcome of this research will be the establishment of a powerful non-invasive imaging platform of the inner ear that will enable us to test hypotheses, in living animals, on how ion transport regulates the endolymph, how disorders of ion transport cause disruption of endolymphatic fluid, and how the expression of different biomarkers lead to disorders of ion transport.

Lina Reiss, Ph.D.

Lina Reiss, Ph.D.

Oregon Health & Science University
Changes in Residual Hearing in a Hearing-impaired Guinea Pig Model of Hybrid Cochlear Implants (CIs)

The goal of the current study is to understand mechanisms of hearing loss with “hybrid” or “electro-acoustic” cochlear implants (CIs), a new type of CI designed to preserve low-frequency hearing and allow combined acoustic-electric stimulation in the same ear. Hybrid CI users perform significantly better than standard CI users on musical melody recognition, voice recognition, and speech recognition in the presence of background talkers. However, approximately 10% of hybrid CI patients lose all residual hearing, and another 20% lose 20-30 dB after implantation. We hypothesize that in addition to surgical trauma, electrical stimulation through the hybrid CIs also damages cochlear cells, leading to the residual hearing loss (HL). Aim 1 is to determine the contribution of electrical stimulation to the residual HL in hybrid CI guinea pigs with noise-induced steeply-sloping high frequency hearing loss (NIHFHL). Aim 2 is to examine the effect of electrical stimulation on the cochlear pathology. The findings will guide the development of strategies to prevent hearing loss with electrical stimulation, and allow extension of the hybrid concept to all cochlear implant recipients with usable residual hearing.

Research area: Cochlear implants

Long term goal of research: To improve residual hearing preservation with “hybrid” or “electro-acoustic” cochlear implants (CIs), a new type of CI designed to preserve low-frequency hearing and allow combined acoustic-electric stimulation in the same ear.

Michael Roberts, Ph.D.

Michael Roberts, Ph.D.

University of Michigan
Cellular and synaptic basis of binaural gain control through the commissure of the inferior colliculus

Deficits in binaural hearing make it difficult for users of cochlear implants and hearing aids to localize sounds and follow speech in everyday situations. One of the most important sites for binaural computations is the inferior colliculus (IC). Located in the auditory midbrain, the IC is the hub of the central auditory system, receiving most of the ascending output of the auditory brainstem and much of the descending output of the auditory cortex. The left and right lobes of the IC communicate with each other through a massive connection called the commissure. Recent data from in vivo recordings show that commissural projections shape how IC neurons encode sound location. This suggests that important binaural interactions arise through the IC commissure, but the cellular and synaptic basis of these interactions are largely unknown. Understanding these interactions will provide foundational knowledge to guide future efforts to restore binaural hearing.

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