CENTRAL AUDITORY PROCESSING DISORDER (CAPD)
Four grants were awarded for research that will increase our understanding of the causes, diagnosis, and treatment of CAPD, an umbrella term for a variety of disorders that affect the way the brain processes auditory information. All four of our CAPD grantees are General Grand Chapter Royal Arch Masons International award recipients. See all researchers who have received or are currently receiving funding from the Royal Arch Masons
+ Alisha Lambeth Jones, Au.D., Ph.D.
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.
Long-term goal: To identify patterns of deficits in auditory processing, language, and cognition skills for both children and adolescents with a premature birth history. Once patterns of deficits are identified, early intervention treatment as well as a rehabilitation program will be developed to either prevent or treat the deficit areas.
Alisha Lambeth Jones, Au.D., Ph.D., received her clinical doctorate in audiology and doctorate of philosophy in audiology from the University of South Alabama in Mobile. She is an assistant professor at Auburn University in Alabama.
+ 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.
Long-term goal: To better diagnose and treat patients with auditory dysfunction following head injury, thereby minimizing hearing loss, tinnitus, and hyperacusis. The study has implications for a broad range of individuals, including those with isolated head injuries as well as those with repetitive head injuries, such as athletes and military personnel.
Elliott D. Kozin, M.D., received his medical degree at the University of Pennsylvania School of Medicine. An investigator at Massachusetts Eye and Ear, Harvard Medical School, in Boston, he also received research training at the National Institute on Deafness and Other Communication Disorders, National Institutes of Health.
+ 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.
Long term goal: To systematically examine the optimal combination of hearing aids and behavioral and pharmacological approaches to delay or prevent the declines in complex sound processing seen in presbycusis.
Dr. Khaleel Razak received his doctorate in neuroscience from the University of Wyoming. He is an associate professor of psychology and neuroscience at the University of California, Riverside.
+ Joseph Toscano, Ph.D.
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.
Long-term goal: To develop a clinical test for identifying auditory neuropathy and other types of hearing loss that can be used for both adults and children.
Joseph Toscano, Ph.D., received his doctorate in cognitive psychology from the University of Iowa, and was a postdoctoral fellow at the Beckman Institute for Advanced Science and Technology at the University of Illinois Urbana–Champaign. He is an assistant professor of psychological and brain sciences at Villanova University, in Pennsylvania, where he directs the Word Recognition and Auditory Perception Lab.
HHF awarded six grants for the best overall hearing research proposals. These grants were generously supported by the board of HHF as well as supporters who designated their gifts to fund the most promising hearing research.
+ 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.
Long-term goal: To identify CVD risk factors that may contribute to hearing loss and to develop clinical tools to assess at-risk individuals.
Rachael R. Baiduc, Ph.D., MPH, received both her doctorate in communication sciences and disorders and her master’s degree in public health from Northwestern University, Illinois. She is an assistant professor in the department of speech, language, and hearing sciences at the University of Colorado Boulder.
+ 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.
Long-term goal: To better understand basic auditory mechanisms that are affected by background noise in order to improve hearing aid algorithm design and hearing loss treatment outcomes.
Evelyn Davies-Venn, Au.D., Ph.D., received her master’s degree and doctorate of audiology as well as a Ph.D. in audiology all from the University of Washington, and completed postdoctoral training at Purdue University, Indiana. She is an assistant professor in the department of speech-language and hearing sciences at the University of Minnesota. Her ERG grant was partially funded by an anonymous donor.
+ 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.
Long-term goal: To reveal general principles of how brain cells encode sensations from the inner ear and how the brain initiates responses when stability is lost, in order to inform therapeutic strategies to treat balance deficits.
David Ehrlich, Ph.D., received his doctorate in neuroscience at Emory University in Atlanta, and was a neuroscience research fellow at the Hospital for Sick Children in Toronto. He is a postdoctoral fellow in the department of otolaryngology–head and neck surgery and the Neuroscience Institute at the New York University School of Medicine. David Ehrlich, Ph.D.’s grant is partially supported by the Meringoff Family Foundation, a New York City–based organization whose mission is to improve the lives of local children through support of education, research, and public health.
+ 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.
Long-term goal: To identify a key pathway or a key leukocyte subset that regulates ototoxicity or protection, in order to design a therapeutic strategy to prevent or cure ototoxicity, which may be applicable for hearing loss generally.
Soumen Roy, Ph.D., received his master’s degree in biosciences from Mangalore University, India, and his doctorate in hearing research and targeted nanoscience from University of Innsbruck, Austria. He is a research fellow at the National Cancer Institute, National Institutes of Health.
+ 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.
Long-term goal: To explore the mechanisms by which TRPA1 activation modifies cochlear mechanics and hearing sensitivity, in order to uncover new therapeutic targets to prevent hearing loss or tinnitus.
A. Catalina Vélez-Ortega, Ph.D., received her master’s in biology from the University of Antioquia, Colombia, and her doctorate in physiology from the University of Kentucky, where she completed postdoctoral training and is now an assistant professor in the department of physiology. Dr. Vélez-Ortega's ERG grant was generously funded by Cochlear.
+ 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.
Long-term goal: To understand the molecular mechanisms of synaptic transmission in the inner ear and the effects of noise exposure on this transmission process, in order to find methods to protect hair cell synaptic function and prevent hearing loss.
Philippe Vincent, Ph.D., received his doctorate in cell biology and physiopathology from the University of Bordeaux, France. He is a postdoctoral fellow in the department of otolaryngology–head and neck surgery at Johns Hopkins University in Baltimore.
One grant was awarded focused on research (e.g., animal models, brain imaging, biomarkers, electrophysiology) that will increase our understanding of the mechanisms, causes, diagnosis, and treatments of hyperacusis and severe forms of loudness intolerance. This grant was funded by Hyperacusis Research.
+ 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.
Long-term goal: To broaden our understanding of the neural mechanisms underlying loudness perception in order to find a potential therapeutic target to correct, or mitigate, bothersome hyperacusis.
Kelly Radziwon, Ph.D., received her doctorate in cognitive sychology at the University at Buffalo, the State University of New York, where she is conducting postdoctoral work at its Center for Hearing and Deafness. She is also a 2015 ERG recipient funded by Hyperacusis Research Ltd.
HEARING LOSS IN CHILDREN
One grant was awarded for innovative research focused on congenital and acquired childhood hearing loss and its etiology, assessment, diagnosis and treatment. This grant was generously supported by our partner The Children's Hearing Institute.
+ 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.
Long-term goal: To improve CI performance by combining models of electric field potential with biophysical models of auditory nerve fibers, and to better understand hearing loss mechanisms by detailing the anatomy and electrophysiology of inner ear sensory hair cells.
Babak Vazifehkhahghaffari, Ph.D., received his master’s degree in electrical engineering from the Sharif Institute of Technology, Iran, and his doctorate in computational neuroscience from University of Technology, Malaysia. He is a postdoctoral research associate in the department of otolaryngology at Washington University in St. Louis.
Two grants were awarded for innovative research that will increase our understanding of the inner ear and balance disorder Ménière's Disease. They were generously supported by a family committed to finding treatments and cures for Ménière's Disease.
+ 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.
Gail Ishiyama received her medical degree from the David Geffen School of Medicine at UCLA, where she completed a two-year postdoctoral research fellowship under head and neck surgery - neurotology to understand the neurochemistry of the auditory and vestibular system, and where she is now a clinician-scientist in the department of neurology. Dr. Ishiyama was also a 2016 Emerging Research Grants recipient.
+ Ian Swinburne, Ph.D.
Harvard Medical School
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.
Ian Swinburne received his Ph.D in Cell Biology from Harvard Medical School, where he studied gene regulation and the role of intron length on biological timing with Pamela Silver. He currently conducts research at Harvard Medical School on systems biology of the inner ear with Sean Megason. Notably, his imaging and genetic analyses revealed the mechanism by which the endolymphatic sac behaves like a relief valve to control inner ear pressure and volume. His goal is to identify the molecular basis of the relief valve physiology. Dr. Swinburne was also a 2013 Emerging Research Grants recipient.
Two grants were awarded for innovative research that will increase our understanding of the mechanisms, causes, diagnosis, and treatment of tinnitus.
+ 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.
Long-term goal: To develop novel therapies for hearing loss, tinnitus, and hyperacusis, by better understanding how hearing loss occurs in the first place and identifying ways to prevent it.
David Jung, M.D., Ph.D., received his medical degree and his doctorate in genetics from Harvard Medical School, where he is now an assistant professor of otolaryngology. He is also an attending surgeon at Massachusetts Eye and Ear.
+ 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.
Long-term goal: To investigate neuronal activity in the VCN in order to eventually help prevent and treat tinnitus.
Tenzin Ngodup, Ph.D., received his doctorate in neuroscience from the State University of New York at Buffalo and is now a postdoctoral fellow at the Oregon Hearing Research Center at Oregon Health & Science University. Dr. Ngodup received the Les Paul Foundation Award for Tinnitus Research.
One grant was awarded for research to increase our understanding of the mechanisms, causes, diagnosis, and treatments of Usher syndrome, the most common cause of combined blindness and deafness. This grant was generously supported by funders who designated their gifts to fund Usher Syndrome research.
+ 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.
Long-term goal: To understand the molecular architecture of the hair bundle and to decipher the molecular basis for genetic abnormalities leading to deafness, in order to decipher the functioning of the auditory and vestibular system in greater clarity.
Clive Morgan, Ph.D., received his doctorate in biochemistry from University College London. After completing postdoctoral research there and at the University of Manchester in the U.K., he is currently at Oregon Health & Science University with Peter Barr-Gillespie, Ph.D.