2018

Rachael R. Baiduc, Ph.D., MPH

Rachael R. Baiduc, Ph.D., MPH

University of Colorado Boulder
Hearing loss and cardiovascular disease risk burden: epidemiological and physiological data

Although hearing loss is often considered in isolation, recent evidence points toward comorbidity with other conditions including cardiovascular disease (CVD). Both hearing loss and CVD are prevalent chronic conditions, and the auditory system has a demonstrated vulnerability to cardiovascular-related diseases. Given that audiologists are likely to see patients with co-occurring conditions, a better understanding of CVD risk factors is useful. This study will use, for the first time, the notion of risk burden to explore the link between CVD and hearing loss in a large dataset, and will examine the link using specific measures of auditory status in a cross-sectional study. Through the use of cost-effective, clinically available techniques in conjunction with epidemiological data, a greater understanding of CVD risk factors that contribute to hearing loss will be a key toward prevention, early identification, and treatment.

Evelyn Davies-Venn, Au.D., Ph.D

Evelyn Davies-Venn, Au.D., Ph.D

University of Minnesota
Behavioral and neural correlates of amplification outcome

Understanding individual factors, beyond hearing thresholds, that account for the high variability in success in the use of hearing aids is an important question with immediate clinical implications. This project aims to evaluate how fundamental aspects of auditory processing interact with high-intensity sounds and influence hearing aid amplification outcomes. Behavioral and speech and non-speech measures will be used to determine how spectral auditory processing interacts with high intensity sounds and influences amplification. This will help us determine factors that contribute to diminished speech perception in noisy environments for individuals with hearing loss and how their perception of amplified speech can be enhanced in noisy environments.

David Ehrlich, Ph.D

David Ehrlich, Ph.D

New York University School of Medicine
Neural computations for vestibular control of movement initiation

Loss of balance and falls are common in aging populations and associated with various neurological disorders. Balance is sensed using vestibular organs in the inner ear and processed in the brainstem. However, it remains unclear how the brainstem transforms sensations of instability into corrective movements that restore balance. The objective of this project is to define how cells in the brainstem act collectively to produce rapid responses to sensations of instability. In order to measure balance responses in populations of cells located deep within the brain, this project will apply cutting-edge microscopy techniques to the zebrafish. These fish swim to remain balanced, providing a model for balance control and brainstem function in general.

Gail Ishiyama, M.D.

Gail Ishiyama, M.D.

UCLA David Geffen School of Medicine
Cellular and molecular biology of the microvasculature in the macula utricle of patients diagnosed with Ménière’s disease

To investigate the microscopic structure of the vasculature (blood vessel system) of balance organs from patients with intractable Ménière’s disease. Ishiyama’s hypothesis is that altered biochemical pathways affecting the vasculature of the blood labyrinthine barrier—which protects the inner ear from toxins and infections—may cause a dysfunction of the inner ear, leading to hearing loss and vertigo.

Ishiyama’s recent research revealed structural cellular changes in the blood labyrinthine barrier of the utricle, a balance organ, in Ménière’s patients. This project continues the work by detailing the cells and biochemical pathways that are altered in Ménière’s disease. This will provide greater information on the blood labyrinthine barrier and allow for the development of interventions that prevent the progression of hearing loss and stop the disabling vertigo in Ménière’s disease patients.

Alisha Lambeth Jones, Au.D., Ph.D.

Alisha Lambeth Jones, Au.D., Ph.D.

Auburn University
Evaluating central auditory processing (CAP), language, and cognition skills in adolescents born prematurely

This project will recruit 60 adolescents ages 12 to 15 years old with and without a premature birth history. Participants will complete a hearing evaluation, auditory processing evaluation, language evaluation, and cognition evaluation. The overall goal of the project is to determine if there are significant differences in auditory processing, language, and cognition skills among adolescents with a preterm birth history when compared with adolescents with a full-term birth history.

David Jung, M.D., Ph.D.

David Jung, M.D., Ph.D.

Massachusetts Eye and Ear, Harvard Medical School
Mechanisms and development of novel small molecule treatments for cochlear synaptopathy

Inner ear sensory hair cells detect sound vibrations in the inner ear and pass these signals to inner ear neurons, which ultimately send the signals to the brain. The synaptic connections between inner hair cells and neurons (nerve cells) can be lost from noise exposure, aging, or both. The loss of these connections results in what has been termed “hidden” hearing loss because it may be undetected via traditional auditory measures, and it may also be associated with other hearing disorders such as tinnitus and hyperacusis. To reestablish synaptic connections, we have developed a novel way to anchor special molecules that promote synaptic regeneration into the bone of the inner ear, to maximize the stimulation of inner ear neurons.

Elliot Kozin, M.D.

Elliot Kozin, M.D.

Massachusetts Eye and Ear, Harvard University
Evaluation of hearing loss and quality of life in patients with mild traumatic brain injury

This project will focus on auditory dysfunction following head injury, and findings will provide information about the pathophysiology of hearing loss after mild traumatic brain injury (TBI). To date, little has been described on this topic. We aim to assess auditory symptoms and their association with quality-of-life metrics in patients with mild TBI using patient-reported outcome measures. We further plan to analyze objective audiometric tests to understand the nature and severity of auditory dysfunction. Findings will be applied to clinical guidelines that address at-risk patients and the need for monitoring via audiometric testing. We anticipate findings will generate important discussion regarding an often-overlooked area of health effects following head injury.

Clive Morgan, Ph.D.

Clive Morgan, Ph.D.

Oregon Health & Science University
Characterization of Usher syndrome 1F protein complexes

Much of our current knowledge on the molecular makeup of the hair bundle has origins in genetic studies. Several key genes have been discovered but are limited to those genes that are absolutely required for hearing and dispensable in other systems. Many independent genetic mutations also occur in a handful of genes, so that finding new genes can be quite difficult and expensive. My colleague Peter Barr-Gillespie, Ph.D., has pioneered the use of hair bundle isolation techniques to allow studies of the hair bundle proteome, allowing us to uncover many of the features of the hair bundle in single experiments. The next step is to look at how these proteins interact to fulfill the functions of a mechanically sensitive hair bundle and the effects of genetic abnormalities on the whole bundle proteome (set of proteins). In this project I will analyze individual protein complexes using a new hair bundle isolation strategy that allows us to isolate and analyze protein complexes from the hair bundle. I will perform a comparative analysis of the makeup of all Usher syndrome protein complexes. This will shed new light on the proteins involved directly in mechanotransduction.

Tenzin Ngodup, Ph.D.

Tenzin Ngodup, Ph.D.

Oregon Health & Science University
Discovery of novel inhibitory cell types in the cochlear nucleus

Excessive neuronal electrical activity, or hyperactivity, is believed to underlie tinnitus. While many studies on hyperactivity have focused on a region called the dorsal cochlear nucleus, an auditory processing region in the brainstem, very little attention has been given to the ventral cochlear nucleus (VCN). This is surprising since the VCN is likely required for the activation of higher auditory centers in the brain. One likely cause of hyperexcitability is an imbalance between excitatory and inhibitory neuronal connections, or synapses. With the use of genetically modified mouse lines, we are able to reveal that the diversity of inhibitory cell types and circuitry within the VCN is far richer than previously described. Our primary goal is to discover and study the functional significance of these novel inhibitory neurons in the VCN whose inhibitory action, if compromised, could lead to hyperactivity and auditory dysfunction.

Kelly Radziwon, Ph.D.

Kelly Radziwon, Ph.D.

State University of New York at Buffalo
Noise-induced hyperacusis in rats with and without hearing loss

Hyperacusis is an auditory perceptual disorder in which everyday sounds are perceived as uncomfortably or excruciatingly loud. Researchers and audiologists assess hyperacusis in the clinic by asking patients to rate sounds based on their perceived loudness, resulting in a measure known as a loudness discomfort level (LDL). Loudness discomfort ratings are a useful clinical tool, but in the lab we cannot ask animals to “rate” sounds. Instead, to measure loudness perception in animals, our lab trains rats to detect a variety of sounds of varying intensity. By measuring how quickly the animals respond to each sound—faster in reaction to higher intensity sounds and more slowly to lower intensity sounds—we can obtain an accurate picture of perceived loudness in animals. By comparing electrophysiological recordings with behavioral performances of the individual animals, this project aims to characterize the relationship between changes in neural activity and loudness perception in animals with and without noise-induced hearing loss.

The relationship between pain-associated proteins in the auditory pathway and hyperacusis

Hyperacusis is a condition in which sounds of moderate intensity are perceived as intolerably loud or even painful. Despite the apparent link between pain and hyperacusis in humans, little research has been conducted directly comparing the presence of inflammation along the auditory pathway and the occurrence of hyperacusis. One of the major factors limiting this research has been the lack of a reliable animal behavioral model of hyperacusis. However, using reaction time measurements as a marker for loudness perception, I have successfully assessed rats for drug-induced hyperacusis and, more recently, noise-induced hyperacusis. Briefly, the animals will be trained to detect noise bursts of varying intensity. As in humans, the rats will respond faster with increasing sound intensity. Following drug administration or noise exposure, rats will be deemed to have hyperacusis if they have faster-than-normal reaction times to moderate and high-level sounds. Therefore, the goal of the proposed research is to correlate the presence of pain-related molecules along the auditory pathway with reliable behavioral measures of drug and noise-induced hyperacusis.

Khaleel Razak, Ph.D.

Khaleel Razak, Ph.D.

University of California, Riverside
Age-related hearing loss and cortical processing

Presbycusis (age-related hearing loss) is one of the most prevalent forms of hearing impairment in humans, and contributes to speech recognition impairments and cognitive decline. Both peripheral and central auditory system changes are involved in presbycusis. The relative contributions of peripheral hearing loss and brain aging to presbycusis-related auditory processing declines remain unclear. This project will address this question by comparing genetically engineered, age-matched mice with one group experiencing presbycusis and a second group that does not. Spectrotemporal processing (such as speech processing) will be studied as an outcome measure.

Soumen Roy, Ph.D.

Soumen Roy, Ph.D.

National Cancer Institute
High-dimensional analysis of cochlear immunity and cisplatin-induced inflammation

Cisplatin is a life-saving chemotherapy drug but has serious side effects, including causing hearing loss in 40 to 80 percent of cancer patients. Cisplatin enters the cochlea through systemic circulation and gains access to inner ear sensory hair cells after disrupting the protective blood-labyrinth-barrier (BLB). A damaged BLB also means a greater invasion of CD45(+) leukocytes (white blood cells), causing inflammation and, ultimately, hearing loss. We hypothesize that a defined subset of innate immune cells regulates hair cell death by controlling cisplatin-induced inflammatory pathways within the cochlea. Our preliminary data suggest that the cochlea has a different amount of defined leukocytes compared with blood-borne leukocytes. In addition, the data suggest that immune cells that regulate cochlear inflammation may play a role in overall ototoxicity. Understanding cochlear immunity and the interaction of immune cells with other sensory cells will shed light on ototoxicity research and its prevention.

Ian Swinburne, Ph.D.

Ian Swinburne, Ph.D.

Harvard Medical School
Development and Physiology of the Endolymphatic Duct and Sac in Zebrafish

Abnormalities in our sense of hearing and balance are incapacitating in the extreme, and, when subtle, cause psychological distress. Meniere’s disease is an inner ear disease with unclear causes that is inferred from episodes of vertigo, hearing loss, tinnitus, and the sensation of fullness in the ear that can last two to four hours. An unstable inner ear environment is believed to underlie Meniere’s disease. Recently, Swinburne has developed methods to image the live development and physiology of the portion of the Zebrafish ear conserved in humans and believed to be dysfunctional in Meniere’s disease: the endolymphatic duct and sac. With these methods, Ian hopes to gain basic understanding of how the inner ear’s environment is normally maintained and how a defect can lead to a disease.

Classifying the endolymphatic duct and sac cell types and their gene sets using high-throughput single-cell transcriptomics

To understand how the inner ear endolymphatic duct and sac stabilize the inner ear’s environment and to identify ways to restore or elevate this function to mitigate or cure Ménière's disease. The endolymphatic duct and sac play important roles in stabilizing a fluid composition necessary for sensing sound and balance. The recurrent vertigo in Ménière's is likely caused by a malfunction of the endolymphatic sac, causing volume or pressure changes in the inner ear.

Swinburne recently found that the typical-functioning endolymphatic sac periodically inflates and deflates like a balloon, and that specialized cell structures in the sac appear to transiently open, causing the deflation of the endolymphatic sac. The sac, then, appears to act as a relief valve to maintain a consistent volume and pressure within the inner ear. This project will generate a list of endolymphatic sac cell types and the genes governing their function, which will aid in Ménière's diagnosis (which can be delayed due to the range of fluctuating symptoms) and the development of a targeted drug or gene therapy.

Joseph Toscano, Ph.D.

Joseph Toscano, Ph.D.

Villanova University
Cortical EEG measure of speech sound encoding for hearing assessment

Accurate speech recognition depends on fine-grained acoustic cues in the speech signal. Deficits in how these cues are processed may be informative for detecting hearing loss, and particularly for identifying auditory neuropathy, a problem with the way the brain processes sounds. Diagnosing auditory neuropathy in newborns and infants is particularly challenging, as it is often difficult to distinguish it from sensorineural hearing loss using current measurement approaches. Speech tests that measure cortical responses may allow us to overcome this problem. The current project uses electroencephalogram (EEG) techniques to measure brain responses to specific acoustic cues in speech (e.g., the difference between “d” and “t”). These data will be compared with listeners’ speech recognition accuracy, pure-tone audiograms, and self-reported hearing difficulty to determine how these responses vary as a function of hearing status and may be used to detect early stages of hearing loss.

Babak Vazifehkhahghaffari, Ph.D.

Babak Vazifehkhahghaffari, Ph.D.

Washington University in St. Louis
Enhancing cochlear implant performance through development of improved auditory nerve fiber biophysical models with a combined wet lab and dry lab approach

While the cochlear implant (CI) allows access to sound for those with severe hearing loss, perceiving pitch and music and understanding speech in the presence of reverberation, multiple speakers, or background noise remains very limited. To improve the CI, it is important to understand how it affects neuronal (nerve cell) behavior in the inner ear by uncovering the properties of neuronal excitability. Neuronal excitability mainly depends on the movement of different ions through the cell membrane and is affected by components such as ionic currents and ion channels. A more precise model of the auditory nerve combined with models of the CI electric field potential will help improve CI stimulation methods by understanding stimulus-response phenomena and their underlying biophysical mechanisms.

A. Catalina Vélez-Ortega, Ph.D.

A. Catalina Vélez-Ortega, Ph.D.

University of Kentucky
TRPA 1 activation in the cochlea as an intrinsic mechanism of protection against noise-induced hearing loss

TRPA1 is an ion channel mostly known for its role as an “irritant sensor” in pain-sensing neurons. Functional TRPA1 channels are also expressed in the inner ear. However, given that genetically modified mice lacking TRPA1 channels have typical hearing and balance, the role of these channels in the inner ear remains unknown. Noise exposure leads to the production of some of the cellular “irritants” that activate TRPA1 channels. Therefore, we hypothesized that TRPA1 channels are able to sense noise-induced damage in the cochlea. When we exposed adult mice to mild noise levels, we observed a temporary increase in hearing thresholds that lasted several days (making it harder to hear soft sounds). Mice lacking TRPA1 channels, however, recovered significantly faster than mice with typical TRPA1 expression. This project will explore whether, after noise exposure, TRPA1 activation contributes to the temporary shift in hearing thresholds to allow the cochlea enough time to repair or recover from the noise-induced tissue damage. This project will help us better understand the protective effects of TRPA1 activation after noise exposure, and the specific cell types within the inner ear that are involved in this process.

Philippe Vincent, Ph.D.

Philippe Vincent, Ph.D.

Johns Hopkins University
Investigating mechanisms of degeneration of ribbon synapses between auditory inner hair cells and type 1 afferent nerve fibers after noise trauma in mammals

Sensory hair cells in the inner ear pick up the sound signal and transmit it to auditory nerve fibers through chemical synapses by releasing the transmitter glutamate; auditory nerve fibers then transmit the sound-coding signal to the brain. Sound intensity is encoded by the amount of glutamate released by the hair cell, leading to glutamate receptor activation and then action potential firing in auditory nerve fibers. During noise exposure, auditory nerve fiber endings can be damaged short- or long-term, most likely due to an excessive influx of calcium. This phenomenon is called excitotoxicity, but the underlying mechanisms are not completely understood. This project will investigate molecular mechanisms of synaptic transmission between hair cells and auditory nerve fibers and how they are affected after noise trauma.

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