2022

Timothy Balmer, Ph.D.

Timothy Balmer, Ph.D.

Arizona State University
The role of unipolar brush cells in vestibular circuit processing and in balance

The cerebellum receives vestibular sensory signals and is crucial for balance, posture, and gait. Disruption of the vestibular signals that are processed by the vestibular cerebellum, as in the case of Ménière’s disease, leads to profound disability. Our lack of understanding of the circuitry and physiology of this part of the vestibular system makes developing treatments for vestibular disorders extremely difficult. This project focuses on a cell type in the vestibular cerebellum called the unipolar brush cell (UBC). UBCs process vestibular sensory signals and amplify them to downstream targets. However, the identity of these targets and how they process UBC input is not understood. In addition, the role of UBCs in vestibular function must be clarified. The experiments outlined here will identify the targets of UBCs, their synaptic responses, and the role of UBCs in balance. A better understanding of vestibular cerebellar circuitry and function will help us identify the causes of vestibular disorders and suggest possible treatments for them.

Long-term goal: To develop a better understanding of the neural circuits that underlie vestibular function. A more complete understanding of the circuitry and physiology of the vestibular cerebellum is necessary to develop therapies for vestibular dysfunction caused by peripheral disorders such as Ménière’s disease.

James W. Dias, Ph.D.

James W. Dias, Ph.D.

The Medical University of South Carolina
Neural determinants of age-related change in auditory-visual speech processing

Older adults typically have more difficulty than younger adults identifying the speech they hear, especially in noisy listening environments. However, some older adults demonstrate a preserved ability to identify speech that is both heard and seen. This preserved audiovisual speech perception by older adults is not explained by an improved ability to speechread (lipread), as speechreading also typically declines with age. Instead, older adults can exhibit an improved ability to integrate information available from across auditory and visual sources. This behavioral evidence is consistent with findings suggesting that the neural processing of audiovisual speech can improve with age. Despite the accumulating and intriguing evidence, the underlying changes in brain structure and function that support the preservation of audiovisual speech perception in older adults remains a critical knowledge gap. This project uses an innovative neural systems approach to determine how age-related changes in cortical structure and function, both within and between regions of the brain, can preserve audiovisual speech perception in older adults.

Subong Kim, Ph.D.

Subong Kim, Ph.D.

Purdue University
Influence of individual pathophysiology and cognitive profiles on noise tolerance and noise reduction outcomes

Listening to speech in noisy environments can be significantly challenging for people with hearing loss, even with help from hearing aids. Current digital hearing aids are commonly equipped with noise-reduction algorithms; however, noise-reduction processing introduces inevitable distortions of speech cues while attenuating noise. It is known that hearing-impaired listeners with similar audiograms react very differently to background noise and noise-reduction processing in hearing aids, but the biological mechanisms contributing to that variability is particularly understudied.

This project is focused on combining an array of physiological and psychophysical measures to obtain comprehensive hearing and cognitive profiles for listeners. We hope this approach will allow us to explain individual noise tolerance and sensitivity to speech-cue distortions induced by noise-reduction processing in hearing aids. With these distinct biological profiles, we will have a deeper understanding of individual differences in listeners and how those profiles affect communication outcomes across patients who are clinically classified with the same hearing status. This study’s results will assist in the development of objective diagnostics for hearing interventions tailored to individual needs.

Manoj Kumar, Ph.D.

Manoj Kumar, Ph.D.

University of Pittsburgh
Signaling mechanisms of auditory cortex plasticity after noise-induced hearing loss

Exposure to loud noises is the most common cause of hearing loss, which can also lead to hyperacusis and tinnitus. Despite the high prevalence and adverse consequences of noise-induced hearing loss (NIHL), treatment options are limited to cognitive behavioral therapy and hearing prosthetics. Therefore, to aid in the development of pharmacotherapeutic or rehabilitative treatment options for impaired hearing after NIHL, it is imperative to identify the precise signaling mechanisms underlying the auditory cortex plasticity after NIHL. It is well established that reduced GABAergic signaling contributes to the plasticity of the auditory cortex after the onset of NIHL. However, the role and the timing of plasticity of the different subtypes of GABAergic inhibitory neurons remain unknown. Here, we will employ in vivo two-photon Ca2+ imaging and track the different subtypes of GABAergic inhibitory neurons after NIHL at single-cell resolution in awake mice. Determining the inhibitory circuit mechanisms underlying the plasticity of the auditory cortex after NIHL will reveal novel therapeutic targets for treating and rehabilitating impaired hearing after NIHL. Also, because auditory cortex plasticity is associated with hyperexcitability-related disorders such as tinnitus and hyperacusis, a detailed mechanistic understanding of auditory cortex plasticity will highlight a pathway toward the development of novel treatments for these disorders.

,

Matthew Masapollo, Ph.D.

,
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.

,

Robert Raphael, Ph.D.

,
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.

,

Pei-Ciao Tang, Ph.D.

,
Pei-Ciao Tang, Ph.D.

University of Miami Miller School of Medicine
Elucidating the development of the otic lineage using stem cell-derived organoid systems

One of the main causes of hearing loss is the damage to and/or loss of specialized, cochlear hair cells and neurons, which are ultimately responsible for our sense of hearing. Stem cell–derived 3D inner ear organoids (lab-grown, simplified mini-organs) provide an opportunity to study hair cells and sensory neurons in a dish. However, the system is in its infancy, and hair cell–containing organoids are difficult to produce and maintain. This project will use a stem cell–derived 3D inner ear organoid system as a model to study mammalian inner ear development. The developmental knowledge gained will then be used to optimize the efficacy of the organoid system. As such, the results will progress our understanding of how the inner ear forms and functions, with the improved organoid system then allowing us directly to elucidate the factors causing the congenital hearing loss.

,

Ross Williamson, Ph.D.

,
Ross Williamson, Ph.D.

University of Pittsburgh
Characterizing tinnitus-induced changes in auditory corticofugal networks

The irrepressible perception of sounds without an external sound source is a symptom that is present in a number of different auditory dysfunctions. It is the primary complaint of tinnitus sufferers, who report significant “ringing” in the ears, and it is one of the primary sensory symptoms present in schizophrenia sufferers who “hear voices.” Tinnitus is thought to reflect a disorder in gain: A loss of input at the periphery shifts the balance of excitation and inhibition throughout the auditory hierarchy leading to excess hyperexcitability, which then leads to the perception of phantom sounds. This project aims to quantify how such “phantom sound” signals are routed and broadcast across the entire brain, and to understand how these signals impact our ability to perceive sound. Identifying improper regulation of brain-wide neural circuits in this way will provide a foundation for the development of new treatments for tinnitus and other hearing disorders.

Megan Beers Wood, Ph.D.

Megan Beers Wood, Ph.D.

Johns Hopkins University School of Medicine
Type II auditory nerve fibers as instigators of the cochlear immune response after acoustic trauma

A subset of patients with hyperacusis experience pain in the presence of typically tolerated sound. Little is known about the origin of this pain. One hypothesis is that the type II auditory nerve fibers (type II neurons) of the inner ear may act as pain receptors after exposure to damaging levels of noise (acoustic damage). Our lab has shown that type II neurons share key characteristics with pain neurons: They respond to tissue damage; they are hyperactive after acoustic damage; and they express genes similar to pain neurons, such as the gene for CGRP-alpha. However, type II neurons are not the only cell types that respond to acoustic damage. The immune system responds quickly after damaging noise exposure. In other systems of the body such as the skin, CGRP-alpha can affect immune cell function. This project looks at the expression of CGRP-alpha in type II neurons after noise exposure. CGRP-alpha will be blocked during noise exposure to see if this affects the immune response to tissue damage.

Sign up to receive groundbreaking hearing and balance research updates.