Kristi Hendrickson, Ph.D., CCC-SLP

Kristi Hendrickson, Ph.D., CCC-SLP

University of Iowa
Neural correlates of semantic structure in children who are hard of hearing

Mild to severe hearing loss places children at risk for delays in language development. One aspect of language that is affected is vocabulary development; children who are hard of hearing tend to know less about word meanings than their typical hearing peers. This gap in vocabulary skills is crucial because vocabulary is one of the strongest predictors of academic achievement. Therefore, it is essential to examine factors that are both: 1) amenable to change through intervention, and 2) influence vocabulary knowledge, in order to help close the vocabulary gap. One such factor is semantic memory structure (i.e., how the brain groups concepts with common properties). In essence, semantic structure determines how individuals understand and interact with the social and physical world. Yet, very little is known about how children with hearing loss structure semantic information in the brain. This project addresses a critical need by characterizing semantic structure in the brains of children who are hard of hearing, and results will inform vocabulary interventions. Given the predictive validity of vocabulary knowledge for academic achievement, improving vocabulary understanding in children with hearing loss has the potential to impact all aspects of language (form, content, and use).

Ronna Hertzano, M.D., Ph.D.

Ronna Hertzano, M.D., Ph.D.

University of Maryland School of Medicine

A new protocol for selective and efficient sorting of the auditory sensory epithelium

The goal of this project is to develop methods for separating and characterizing the unique cell types of the auditory sensory epithelium using methods commonly used by immunologists. This could also result in the identification of new cell type-specific proteins and possibly new deafness genes.

Nathan Higgins, Ph.D.

Nathan Higgins, Ph.D.

Vanderbilt University
Biomarkers of spatial processing in auditory cortex measured with functional near-infrared spectroscopy

Central auditory processing disorders (CAPD) comprise a number of functional deficits, such as impairments in the ability to process complex information used for localizing, fusing, and discriminating acoustic objects or streams. Binaural hearing (integrating information from the two ears) represents a fundamental aspect of central auditory processing and can be objectively measured in the brain using biomarkers such as the blood oxygenation level-dependent (BOLD) signal in the auditory cortex.

Functional near-infrared spectroscopy (fNIRS) is an emerging technique for measuring the BOLD signal, and is well suited for study of CAPD clinically due to its low noise, portability, and cost effectiveness. As a clinical tool for objective measures of central auditory processing, fNIRS has a bright future. This project will measure fNIRS sensitivity to binaural tuning of BOLD responses, testing the hypothesis of broad contralateral tuning as seen with fMRI. Attention will be manipulated by tasks requiring feature detection in different modalities (location, pitch, visual). Also to be measured is the effect of task engagement on the BOLD signal, compared with passive listening, in order to yield an objective biomarker of cortical processing for task-related attention. This is an important tool when examining clinical populations (e.g. young children) who are unable to provide reliable feedback.

Todd A. Hillman, M.D.

Todd A. Hillman, M.D.

Allegheny-Singer Research Institute

Otologic implant polymers for biofilm control in chronic otitis media

Chronic otitis media, including chronic serous otitis media and chronic otorrhea, is a leading cause of hearing loss in the world. This proposal will investigate the role of bacterial biofilms in chronic otitis and explore novel biofilm resistant materials for use in patients with this disease process.

Mingqian Huang, Ph.D.

Mingqian Huang, Ph.D.

Massachusetts General Hospital

Expression and function of Mlf1, a candidate gene involved in both Pou4f3 and pRb pathways, in a zebrafish model

The proposed research is to understand the potential role of Mlf1 gene in hair cell development. Mlf1 has been implicated in the pathways controlled by two hair cell genes, Pou4f3 and pRb, both of which could give rise to deafness if mutated. Therefore dysfunction of Mlf1 may play a role in deafness.

Sung-Ho Huh, Ph.D.

Sung-Ho Huh, Ph.D.

Washington University
Role of FGF's in Cochlear Sensory Epithelium

Congenital sensorineural hearing loss is one of the most common hereditary disabilities, affecting 1 in 1000 children. Fgf20 null mice have congenital hearing loss associated with loss of sensory cells, and inactivation of both Fgf9 and Fgf20 result in a shortened cochlea. The goal of our research is to understand the cellular and molecular functions of Fgf9 and Fgf20 in inner ear development in vivo. The ultimate goal of this research is to learn how to direct the regeneration of malformed or damaged sensory tissue to restore or improve hearing.

Research area: hair cell regeneration

Long-term goal of research: My long term goal is to understand how Fgf signaling regulates the development, maintenance and repair of sensory hair cells and supporting cells in the cochlea. Due to lack of regenerative ability in humans after loss or dammage of hair cells, it is critical to identify signals that can reactivate developmental pathways and thus permit repair and regeneration of the damaged cochlea. Studying the mechanisms that regulate cochlear development will provide valuable clues about molecules that can be tested for regenerative activity and will thus benefit future translational studies aimed at inducing hair cell regeneration in adult humans.

Elizabeth A. Hurd, Ph.D.

Elizabeth A. Hurd, Ph.D.

University of Michigan
Investigating the role of Chd7 during noise-induced hearing loss

Mice born with loss of Chd7, the gene mutated in human CHARGE syndrome, exhibity middle ear defects and resistance to acoustic trauma. Preliminary results show that deletion of Chd7 in adult mice (using tamoxifen inducible Cre line) also results in variable resistance to acoustic trauma, even in the absence of middle ear defects. This suggests important functions for Chd7 in regulating hair cells and neuronal integrity in adult cochlea. The objective of this research is to identify how loss of Chd7 influences susceptibility to acoustic trauma in the mature cochlea.

Research area: noise-induced hearing loss (NIHL)

Long-term goal of research: to help identify novel genes and molecular pathways involved in protection from NIHL and provide rationale for designing new therapies.

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.

Israt Jahan, M.B.B.S., PH.D.

Israt Jahan, M.B.B.S., PH.D.

University of Iowa
Misexpression of Neurog1 combined with delayed deletion of Atoh1 provides a novel model

Contemporary research is focusing on the regeneration of hair cells in hearing loss using Atoh1. Reconstitution of the organ of Corti requires proper organization of the two types of hair cells, inner and outer hair cells, as well as supporting cells. Recent data showed that level of Atoh1 determines the degree of survival of different types of hair cells. Jahan’s previous work demonstrated the survival of some organ of Corti-like cells without Atoh1 if replaced by a closely related transcription factor, Neurog1. It is now Jahan’s intent to investigate the effect of Atoh1 substitution with Neurog1 combined with a delayed loss of Atoh1 expression in viable animals. This combined mutant offers for the first time a critical test of presumed causalities of molecular mechanism that may regulate the patterning of the organ of Corti, including hair cell and supporting cell differentiation.

Research area: Hair Cell Regeneration

Long-term goal of research: To define the correct dose and duration of Atoh1 expression for type-specific hair cell development which will provide novel insights into hair cell regeneration.

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Nicole Tin-Lok Jiam, M.D.

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Nicole Tin-Lok Jiam, M.D.

Mass Eye and Ear

Age-specific cochlear implant programming for optimal hearing performance

Cochlear implants (CI) offer life-altering hearing restoration for deafened individuals who no longer benefit from hearing aid technologies. Despite advances in CI technology, recipients struggle to process complex sounds in real-world environments, such as speech-in-noise and music. Poor performance results from artifacts of the implants (e.g., adjacent channel interaction, distorted signal input) and age-specific biological differences (e.g., neuronal health, auditory plasticity). Our group determined that children with CIs require a better signal input than adults with CIs to achieve the same level of performance. Additional evidence demonstrates that auditory signal blurring in adults is less impactful on performance outcomes. These findings imply that age should be considered when programming a CI. However, the current clinical practice largely adopts a one-size-fits-all approach toward CI management and uses programming parameters defined by adult CI users. Our project’s main objective is to understand how to better program CIs in children to improve complex sound processing by taking into context the listening environment (e.g., complex sound processing in a crowded room), differences between age groups, and variations in needs or anatomy between individuals.

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.

Wafaa Kaf, M.D., MS.c., Ph.D.

Wafaa Kaf, M.D., MS.c., Ph.D.

Missouri State University
Novel Ménière’s disease diagnosis: extratympanic simultaneous recording of ECochG and ABR to fast click rates using CLAD technique

Ménière’s disease is mainly diagnosed clinically with no available sensitive objective measures to confirm clinical diagnosis. Current auditory electrophysiologic measures such as standard electrocochleography (ECochG) to a slow click rate has low sensitivity that limits its clinical use. Also, standard ECochG to slow rate cannot measure neural adaptation phenomenon (decrease in the neural firing between the inner hair cells and auditory nerve) that occurs in response to continuous presentation of a fast acoustic stimulus. Although other technique modifications of ECochG such as maximum length sequence to fast rate seem to be promising, several limitations in extracting responses to very fast rates exist with this measure that hinder their clinical use for detection of Ménière’s disease. The new continuous loop averaging deconvolution (CLAD) algorithm is a promising technique to extract overlapping auditory evoked responses to very fast rates, providing valuable information about cochlear and neural function of clinical populations. Thus, the use of CLAD with fast rate ECochG and auditory brainstem response (ABR) has the potential to detect early Ménière’s disease by studying the neural adaptation phenomenon. It is hypothesized that Ménière’s disease may show abnormally fast neural adaptation that may manifest as fast degradation of AP and ABR response amplitudes and prolongation of latency as a function of click rate. The current objectives and the long-term goals of this project are to establish and advance ECochG and ABR measures using CLAD technique to identify the critical rate at which neural adaptation starts as a marker for early diagnosis, differential diagnosis and classification of Ménière’s disease.

Christina L. Kaiser, Ph.D.

Christina L. Kaiser, Ph.D.

Boston University School of Medicine

An active role for the supporting cell cytoskeleton in controlling hair cell death and regeneration

Cochlear hair cells are the primary targets of most damaging agents. When these cells are lost in humans and other mammals, the resultant hearing loss is permanent. However, chickens and other avian species have the ability to replace lost cochlear hair cells. Cochlear hair cell regeneration occurs through two different mechanisms: Direct transdifferentiation (DT) and mitotic proliferation. In DT, supporting cells directly alter their gene expression to become new hair cells. Alternatively, in mitotic proliferation, normally quiescent supporting cells are induced to proliferate and differentiate into new hair cells and new supporting cells following the death and ejection of the original sensory cells. The experiments in this research are designed to examine how supporting cells regulate hair cell death and how this subsequently regulates supporting cell proliferation. Additionally, we are trying to prevent both the death and ejection of cochlear hair cells. If cochlear hair cells can be “trapped” and “rescued” by treatment with various inhibitors, these compounds may be useful therapeutic tools in hearing loss prevention.

Alan Kan, Ph.D.

Alan Kan, Ph.D.

University of Wisconsin, Madison
Exploiting the “better ear” in bilateral cochlear implants for improved speech understanding in noisy situations

A recent study investigating selective attention abilities in cochlear implant users may point to a novel new method for improving the understanding of speech in a noisy environment. In that study, cochlear implant users showed significant improvement in speech understanding when instructed to attend to a target talker in one ear and ignore an interfering talker in the other. For some, there was a “better ear” for listening which yielded an even greater improvement. The aim of this work is to evaluate the feasibility of a novel strategy that takes advantage of these observations. A “better ear” strategy is proposed that combines (1) attending to a target talker in the “better ear” with (2) processing that separates the target talker’s speech from a noisy background, and delivers the target talker to the “better ear” and the remaining sound scene to the other ear. We believe this “better ear” strategy will be a significant step towards closing the gap in speech understanding performance between bilateral cochlear implant users and normal hearing listeners, and has the potential to provide significant improvements in speech understanding in noisy situations for patients with bilateral hearing aids, bimodal aids and other types of hearing impairments. Notably, this work is particularly important and relevant for children fitted with cochlear implants since they need to contend with noisy environments, such as classrooms, every day. The ability to hear better in these environments will lead to improved long-term social and educational development for these children.

Research area: Cochlear Implants; Central Auditory Processing Disorder

Long-term goal of research: To close the gap in speech understanding performance between cochlear implant users and normal hearing listeners. The primary outcome of this study will help determine whether the “better ear” strategy will provide a significant benefit for cochlear implant users, and whether this strategy for listening is desirable. Positive results will provide an impetus for the development of new engineering solutions surrounding the implementation of this “better ear” strategy. In addition, our proposed experimental paradigm offers a unique opportunity to study auditory attention mechanisms used in understanding speech in noisy environments. This will help further develop our understanding of the human auditory system so that we can bridge the gap in hearing-in-noise performance between hearing impaired and normal hearing listeners.

HiJee Kang, Ph.D.

HiJee Kang, Ph.D.

Johns Hopkins University

Age-related changes on neural mechanisms in the auditory cortex for learning complex sounds 

In everyday environments, we encounter complex acoustic streams yet we rapidly perceive only relevant information with little conscious effort, such as when having a conversation in a noisy background. With aging, this ability seems to degrade due to disrupted neural mechanisms in the brain. One of the key processes that enable efficient auditory perception is rapid and implicit learning of new sounds through their reoccurrences, allowing our brains to link auditory streams with relevant memories to perceive meaningful information. This process must be conveyed by populations of neurons in relevant brain regions—for hearing, in the auditory cortex. This project focuses on age-related changes in implicit learning. We aim to identify how neuronal activity encodes sensory signals, detects reoccurring stimuli, and ultimately stores reoccurring sensory signals in memory. We will use optical imaging and holographic stimulation to identify changes in a group of neurons in the auditory cortex that are involved in such processes. Our goal is to acquire a comprehensive understanding of the neural circuits involved in learning new sounds in a healthy young population as well as to characterize altered neural circuits caused by aging. 

Ravinder Kaur, Ph.D.

Ravinder Kaur, Ph.D.

Rochester General Hospital Research Institute
Differential Virulence gene expression of S. pneumoniae and Haemophilus influenzae in children with Acute Otitis Media & modulation of innate immune responses

Middle ear infections are the most common infectious disease among children leading to the use of antibiotics. Middle ear infections are typically followed by 4-12 weeks of middle ear effusion during which time children have diminished hearing leading to temporary delayed speech and language development. In developing countries, permanent hearing loss is not uncommon. Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn) are the two main bacteria that cause middle ear infections and are the target for new vaccine development. In the funded research, expression of various vaccine candidate proteins of NTHi and Spn in the nose (where middle ear infections start) and in the middle ear (where infections cause hearing loss) will be compared. Gene expression of the studied NTHi and Spn vaccine targets might be modulated by innate immunity of the host during disease progression and this too will be studied.

Research area: Middle Ear

Long-term goal of research: To develop a vaccine to prevent middle ear infections, thereby reducing hearing loss from this common childhood infection. Towards this goal here we will evaluate several vaccine candidates of the most common causes of middle ear infections to determine whether immunity induced by vaccination will be effective to rid the child of the bacteria when they reside in the nose and/or when they gain entry to the middle ear. We will also study how the gene expression of the studied vaccine targets might be influenced by the child’s immunity system.

Ravinder Kaur, Ph.D. is a Research Scientist at the Rochester General Hospital Research Institute. Kaur’s research focuses on the pathogenesis of middle ear infections and immune response of children to those infections with a goal of facilitating a vaccine to prevent hearing loss.

Judith Kempfle, M.D.

Judith Kempfle, M.D.

Click to download a PDF of Dr. Kempfle’s Meet the Researcher profile.

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.

Yayoi S. Kikkawa, M.D., Ph.D.

Yayoi S. Kikkawa, M.D., Ph.D.

University of Texas Southwestern Medical Center

Molecular and morphological analysis of protocadherin 15 in vestibular stereocilia development

Stereocilia of the inner ear hair cells are micro-scale mechanosensors which convert mechanical forces into electrochemical signals and its precise integrity is critical for hearing and balance. However, the molecular mechanism that regulates stereocilia integrity is not well understood. This proposal focuses on a cadherin-like protein, protocadherin 15 (Pcdh15). Mutations in human Pcdh15 cause Usher syndrome (USH type 1F), the leading cause of combined hearing and vision loss. The molecular characterization of Pcdh15 will lay the foundation for therapeutic strategies not only for Usher syndrome but also for other inner ear disorders associated with abnormalities of hair cell transduction.

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