2017

Timothy Balmer, Ph.D.

Timothy Balmer, Ph.D.

Oregon Health & Science University
Chronic transmitter exposure in excitatory neurons of the cochlear nucleus generates persistent excitation and could underlie tinnitus

The dorsal cochlear nucleus in the brainstem receives not only auditory signals directly from the ear but also multisensory input from other areas of the brain. However, the sources of these inputs are unclear. We do know the inputs are processed through unipolar brush cells (UBC), a type of nerve cell in the cochlear nucleus that amplifies signals. This cell derives its name from its single paintbrush-like dendrite, which shows persistent excitation due to chronic neurotransmitter exposure. My project is to investigate whether problems with the multisensory inputs or with the chronic neurotransmitter at the UBC synapse lead to hyperactivity of the cochlear nucleus, which is associated with tinnitus.

Renee Banakis Hartl, M.D., Au.D.

Renee Banakis Hartl, M.D., Au.D.

University of Colorado, Denver
Effect of deafness duration on the efficacy of cochlear implants for single-sided deafness

One of the large challenges in attempting to predict outcomes of cochlear implantation is due to the diverse clinical characteristics of implant candidates. Our initial studies have worked to isolate the effect of one variable (duration of deafness) in a specific etiology (single-sided deafness) on implant efficacy. By studying auditory neurophysiological responses to cochlear implant stimulation in an animal model for single-sided deafness, we can investigate objective performance and changes in brainstem physiology.

Joseph H. Bochner, Ph.D.

Joseph H. Bochner, Ph.D.

Rochester Institute of Technology
Auditory Experience, Critical Periods, and the Development of Categorical Perception in Cochlear Implant Users: A Preliminary Investigation

My project will investigate the role of age on the success of cochlear implantation and auditory experience on the development of perceptual (phoneme) categories in prelingually deaf cochlear implant users. The research will demonstrate the degree to which these cochlear implant users can categorize speech sounds, which will improve our understanding of speech perception and the effects of early auditory deprivation on the overall success of cochlear implantation.

Angela Yarnell Bonino, Ph.D., CCC-A

Angela Yarnell Bonino, Ph.D., CCC-A

University of Colorado - Boulder
Toddlers’ and preschoolers’ ability to hear speech in noise: Assessing performance with a two-interval, observer-based procedure

Children require access to acoustic information in order to develop speech and language. However, this information is often degraded because of competing sounds in the environment. While it is clear that children’s ability to listen in noise substantially improve between infancy and entering school, we do not know how and when this process unfolds during the intervening years.

The objective of this project is to develop a reliable behavioral method for measuring speech perception in noise for toddlers and preschoolers. This approach will build upon a recently developed testing method, in which a child’s behavior is judged by an experimenter using a two-interval, two-alternative testing paradigm . The children’s response to the stimulus is further shaped by training them to perform a conditioned play-based response to the sound. The proposed research will test the hypotheses that reliable data can be collected from toddlers and preschoolers and that speech-in-noise abilities improve dramatically during this time period. Results from this project will provide us information on how typical auditory development unfolds during the toddler and preschooler years, which may advance our understanding of the potential underpinnings of auditory processing disorders and the effects of hearing loss.

Inyong Choi, Ph.D.

Inyong Choi, Ph.D.

University of Iowa
Neural correlates of selective listening deficits in a multiple-speaker environment

Choi’s lab studies how human brains understand speech in noisy everyday settings, how central brain functions are affected by hearing loss, and how we can improve hearing-related brain functions with training.

This study will investigate several key neural processing systems required for successful speech communication in noisy social settings, and how neural processing deteriorates in listeners with degraded hearing ability. As such the project involves basic neuroscientific research of the central auditory system and translational research on hearing rehabilitation techniques.

Oscar Diaz-Horta, Ph.D.

Oscar Diaz-Horta, Ph.D.

University of Miami
The role of FAM65B in the regulation of post-translational modifications of auditory hair cell proteins

Recent genetic studies have identified the FAM65B protein as an important molecule for hearing. In this study we will search for inner ear hair cell proteins interacting with FAM65B in order to further delineate FAM65B’s function. We will focus on FAM65B’s role in the modification of its partner proteins. These studies will help characterize molecular aspects of hearing and how hearing loss occurs when they are disrupted.

Ngoc-Nhi Luu, M.D., Dr. Med

Ngoc-Nhi Luu, M.D., Dr. Med

Massachusetts Eye and Ear, Harvard Medical School
Characterization of endolymphatic sac anatomy in early and late onset Ménière's disease: a clinical radiologic study

Ménière’s disease is an inner ear disease that affects the vestibular organs of the inner ear and presents with various symptoms such as vertigo, hearing loss, and tinnitus. There is no known cause, but it is believed that Ménière’s can be associated with an abnormal accumulation of fluid in the inner ear, called endolymphatic hydrops, which is produced in an appendix to the vestibular system, called the endolymphatic sac. Currently, diagnosis of Ménière’s is entirely based on clinical symptoms, and since these can vary greatly in patients and even mimic other diseases, it has made identifying Ménière’s difficult, delaying treatment of symptoms. Previously, using radiologic imaging, we had found striking differences in the vestibular aqueduct, a bony canal that the sac traverses, among those with either early or late-onset Ménière’s. This project is to confirm whether the shape and course of the vestibular aqueduct can act as a reliable biomarker to identify distinct types of Ménière’s in patients.

Senthilvelan Manohar, Ph.D.

Senthilvelan Manohar, Ph.D.

University at Buffalo
Behavioral Model of Loudness Intolerance

High-level noise causes discomfort for typical-hearing individuals. However, following cochlear damage, even moderate-level noise can become intolerable and painful, a condition known as hyperacusis.

One of the critical requirements for understanding and finding a cure for hyperacusis is the development of animal models. I have developed two new animal behavior models to study the pain and annoyance components of hyperacusis. The Active Sound Avoidance Paradigm (ASAP) uses a mouse’s innate aversion to a light open area and preference for a dark enclosed box. In the presence of intense noise, the animal shifts its preference to the light area. The Auditory Nociception Test (ANT) is based on a traditional pain threshold assessment. Although animals show an elevated pain threshold in the presence of 90 and 100 dB, at 110 and 115 dB they show a reduced pain tolerance. Using these two tests together will allow me to assess emotional reactions to sound as well as the neural interactions between auditory perception and pain sensation.

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.

Jennifer Resnik, Ph.D.

Jennifer Resnik, Ph.D.

Mass Eye and Ear, Harvard Medical School
Homeostatic modifications in cortical GABA circuits enable states of hyperexcitability and reduced sound level tolerance after auditory nerve degeneration

Sensorineural hearing loss due to noise exposure, aging, ototoxic drugs, or certain diseases reduce the neural activity transmitted from the cochlea to the central auditory system. These types of hearing loss often give rise to hyperacusis, an auditory hypersensitivity disorder in which low- to moderate-intensity sounds are perceived as intolerably loud or even painful. Previously thought as originating in the damaged ear, hyperacusis is emerging as a complex disorder. While it can be triggered by a peripheral injury, it develops from a maladaptation of the central auditory system to the peripheral dysfunction. My research will test the hypothesis that the recovery of sound detection and speech comprehension, may cause an overcompensation that leads to an increase in sound sensitivity and reduced tolerance of moderately loud sounds.

This hypothesis will be tested using a combination of chronic single-unit recordings, operant behavioral methods and optogenetic interrogation of specific sub-classes of cortical interneurons. By understanding how brain plasticity is modulated, we will gain deeper insight into the neuronal mechanism underlying aberrant sound processing and its potential reversal.

Christina Reuterskiöld, Ph.D.

Christina Reuterskiöld, Ph.D.

New York University
Rhyme Awareness in Children with Cochlear Implants: Investigating the Effect of a Degraded Auditory System on Auditory Processing, Language, and Literacy Development

Successful literacy is critical for a child’s development. Decoding written words is mostly dependent on the child’s processing of speech sounds, requiring a certain level of awareness of speech sounds and words in order to develop literacy skills. If the benefits of early cochlear implantation support the development of central auditory processing skills and phonological awareness, children with cochlear implants (CIs) would be expected to acquire phonological awareness skills comparable to children with typical hearing.

However, past research has generated conflicting results on this topic, which this project will attempt to remedy through investigating rhyme recognition skills and vocabulary acquisition in children who received CIs early in life. With co-principal investigator Katrien Vermeire, Ph.D., we will also shed light on the importance of central auditory processing during a child’s first years of life for developing strong literacy skills.

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.

Sandeep Sheth, Ph.D.

Sandeep Sheth, Ph.D.

Southern Illinois University School of Medicine
Cisplatin-induced oxidative stress down-regulates strial Na+/K+-ATPase and endocochlear potential

Cisplatin is a widely used chemotherapy treatment for various solid tumors. Unfortunately, its use sometimes results in permanent hearing loss. Understanding the pathophysiology of cisplatin ototoxicity (toxicity to the ear) is crucial for the development of novel treatments to combat this serious side effect.

Preliminary studies from our lab suggest that cisplatin appears to reduce the sodium/potassium activity of the cochlear fluid maintained by the stria vascularis, an important tissue in the inner ear, which leads to hearing damage. However, this suppressive effect by cisplatin may be restored through epigallocatechin gallate (EGCG), a green tea extract that is an antioxidant with anti-inflammatory properties. This project aims to investigate the potential of EGCG in the treatment of cisplatin-induced hearing loss.

Xiaodong Tan, Ph.D.

Xiaodong Tan, Ph.D.

Northwestern University
Oto-Protection of Honokiol Against Cisplatin-Induced Ototoxicity

Cisplatin is a common chemotherapy medication known to be ototoxic (damaging to hearing), but most proposed drugs to counteract this side effect compromise the antitumor effects of cisplatin. Honokiol is an antitumor agent derived from the magnolia plant that has been shown to have synergistic effects with cisplatin in cancer treatment because it activates an enzyme that protects healthy cells and suppresses tumor cells. As a result, honokiol may have a strong protective effect for cochlear hair cells. This study will investigate the hearing protective properties of honokiol using tissue cultures in the lab as well as through direct drug administration in an animal model.

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