Research

Mapping Better Hearing

By Vicky Chan

Hearing Health Foundation (HHF) is grateful to the many individuals and organizations who have empowered groundbreaking hearing loss research in the last 60 years. A new interactive map displays every institution in the U.S. where HHF has been fortunate to fund groundbreaking research, yielding outstanding advancements in hearing and balance science. The map also indicates the rates of hearing loss in each state, signaling that additional work is urgently needed.

The colors—light yellow, yellow, green, teal, blue, and purple—represent the rates of hearing loss in each state. The calculations are based off 2015 U.S. Census Data, using estimates from the well-known prevalence of hearing loss among specific demographics. At the lowest end of the range in light yellow, hearing loss affects 13.71% of Colorado’s population. The highest rate was found in Missouri, purple, where the prevalence measured 20.15%. The mean for all states was 18.16%. The numbers signal the significance of hearing loss research.

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Nearly all of the institutions on the map represent recipients of the Emerging Research Grants (ERG) who have carried out investigations related to tinnitus, hyperacusis, Ménière's disease, Usher syndrome, hearing loss in children, Central Auditory Processing Disorder, and strial atrophy.

A few institutions are home to the work of the Hearing Restoration Project’s (HRP) domestic consortium members, who focus on investigating hair cell regeneration as a cure for hearing loss and tinnitus. They conduct research at Baylor College of Medicine, Harvard Medical School, Oregon Health & Science University, Stanford University, Stowers Institute, University of Maryland, University of Michigan, University of Southern California, University of Washington, and Washington University.

By mid-year, the institutions corresponding to HHF’s newly formed Ménière's Disease Grants (MDG) program will be added to the map.

HHF envisions a world in which no one lives with hearing loss and tinnitus—until this is realized, we’ll do everything we can to put more innovative hearing loss research on the map.

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New Method Enables Systematic Study of Hair Cell Loss and Regeneration in Chickens

By Carol Stoll

Most forms of hearing loss are permanent because damage to inner ear sensory hair cells is irreversible in mammals, including humans. Mammalian vestibular hair cells have the potential to regenerate albeit at a low rate, but the hair cells of the adult mammalian cochlea are not regenerated. Birds, however, have a robust regenerative response to hair cell damage and are able to restore structure and function in inner ear organs. Consequently, the study of the molecular mechanisms that trigger the onset of avian hair cell regeneration in the balance organs as well as in the cochlea is important and may lead to therapies for hearing loss in humans.

This image shows the undamaged and damaged utricle, an inner ear balance organ, in a chicken. HRP researchers have devised a new method to study the precise timing of hair cell regeneration in chickens using a single surgical application of an ototoxic drug. Photo by Amanda Janesick, Ph.D.

This image shows the undamaged and damaged utricle, an inner ear balance organ, in a chicken. HRP researchers have devised a new method to study the precise timing of hair cell regeneration in chickens using a single surgical application of an ototoxic drug. Photo by Amanda Janesick, Ph.D.

Past experiments that investigate these regeneration mechanisms in living chickens required multiple injections of a drug to induce hair cell loss, making it difficult to determine the exact timing of the regeneration response. A collaboration of two Hearing Restoration Project researchers, Stefan Heller, Ph.D. and Jennifer Stone, Ph.D., and two talented postdoctoral fellows from their laboratories was recently published in Journal of the Association for Research in Otolaryngology identifying a potential solution to this problem. They developed an experimental framework that uses a single ototoxic drug application, enabling them to study the precise onset and timing of hair cell regeneration in vivo.

Heller, Stone, and colleagues performed their experiments on a total of 75 chickens. At seven days of age, the chickens were anesthetized and underwent surgery to eliminate hair cells in the inner ear organs. During the surgery, streptomycin (an ototoxic antibiotic) was delivered to the chicken’s inner ear. At various time points after the surgery, two sensory organs—the utricle, a vestibular organ; and the basilar papilla, the hearing organ—were dissected, labeled for various cellular markers, and analyzed under a microscope. Hair cells and their surrounding supporting cells were counted and observed for damage. EdU, a marker of cell division, was administered to the chickens to determine whether or not new hair cells were generated by cell division. These techniques enabled the researchers to quantitatively characterize the regenerative response of the utricle after damage.

The results of the study demonstrate that surgical application of a single streptomycin dose is a feasible approach to elicit hair cell loss and regeneration in the chicken utricle and basilar papilla. Just hours after streptomycin delivery, hair cell numbers significantly declined and DNA replication was activated. The team was then able to record specific events of the regeneration process, which get initiated around 12 hours after streptomycin-induced hair cell loss, and continue over the course of several days.

Supporting cells produce new hair cells either by converting into a hair cell (direct transdifferentiation), or by dividing, usually asymmetrically, into a supporting cell and a hair cell.  Throughout this regenerative response, supporting cell numbers and density in the utricle remain relatively constant, suggesting that there is a mechanism that responds to specific levels of damage and coordinates the individual events of the regeneration process.

The study establishes a framework for the refined study of the two modes of hair cell regeneration in the chicken utricle. The next steps of the work will focus on understanding the exact timing and mechanism of coordination of the regeneration response. With only a single application of streptomycin necessary to induce near-complete hair cell loss in hearing and balance organs, the new animal model allows for study of the entire process including initiation, realization, and termination. The fundamental understanding of the avian regenerative mechanisms may lead to future development of therapies for loss of hearing and balance in humans.

Empower the Hearing Restoration Project's life-changing research. If you are able, please make a contribution today.

 
 
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Cortical Alpha Oscillations Predict Speech Intelligibility

By Andrew Dimitrijevic, Ph.D.

Hearing Health Foundation Emerging Research Grants recipient Andrew Dimitrijevic, Ph.D., and colleagues recently published “Cortical Alpha Oscillations Predict Speech Intelligibility” in the journal Frontiers in Human Neuroscience.

The scientists measured brain activity that originates from the cortex, known as alpha rhythms. Previous research has linked these rhythms to sensory processes involving working memory and attention, two crucial tasks for listening to speech in noise. However, no previous research has studied alpha rhythms directly during a clinical speech in noise perception task. The purpose of this study was to measure alpha rhythms during attentive listening in a commonly used speech-in-noise task, known as digits-in-nose (DiN), to better understand the neural processes associated with speech hearing in noise.

Fourteen typical-hearing young adult subjects performed the DiN test while wearing electrode caps to measure alpha rhythms. All subjects completed the task in active and passive listening conditions. The active condition mimicked attentive listening and asked the subject to repeat the digits heard in varying levels of background noise. In the passive condition, the subjects were instructed to ignore the digits and watch a movie of their choice, with captions and no audio.

Two key findings emerged from this study in regards to the influence of attention, individual variability, and predictability of correct recall.

First, the authors concluded that the active condition produced alpha rhythms, while passive listening yielded no such activity. Selective auditory attention can therefore be indexed through this measurement. This result also illustrates that these alpha rhythms arise from neural processes associated with selective attention, rather than from the physical characteristics of sound. To the authors’ knowledge, these differences between passive and active conditions have not previously been reported.

Secondly, all participants showed similar brain activation that predicted when one was going to make a mistake on the DiN task. Specifically, a greater magnitude in one particular aspect of alpha rhythms was found to correlate with comprehension; a larger magnitude on correct trials was observed relative to incorrect trials. This finding was consistent throughout the study and has great potential for clinical use.

Dimitrijevic and his colleagues’ novel findings propel the field’s understanding of the neural activity related to speech-in-noise tasks. It informs the assessment of clinical populations with speech in noise deficits, such as those with auditory neuropathy spectrum disorder or central auditory processing disorder (CAPD).

Future research will attempt to use this alpha rhythms paradigm in typically developing children and those with CAPD. Ultimately, the scientists hope to develop a clinical tool to better assess listening in a more real-world situation, such as in the presence of background noise, to augment traditional audiological testing.

Andrew Dimitrijevic, Ph.D., is a 2015 Emerging Research Grantee and General Grand Chapter Royal Arch Masons International award recipient. Hearing Health Foundation would like to thank the Royal Arch Masons for their generous contributions to Emerging Research Grants scientists working in the area of central auditory processing disorders (CAPD). We appreciate their ongoing commitment to funding CAPD research.

We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.

 
 
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John Brigande provides commentary: Hearing in the mouse of Usher

Oregon Health & Science University

The March issue of Nature Biotechnology brings together a set of articles that provide an overview of promising RNA-based therapies and the challenges of clinical validation and commercialization. In his News and Views essay, “Hearing in the mouse of Usher,” John V. Brigande, Ph.D., provides commentary on two studies in the issue that report important progress in research on gene therapy for the inner ear.

One in eight people in the United States aged 12 years or older has hearing loss in both ears. That figure suggests that, if you don’t have hearing loss, you likely know someone who does. Worldwide, hearing loss profoundly interferes with life tasks like learning and interpersonal communication for an estimated 32 million children and 328 million adults worldwide. Inherited genetic mutations cause about 50 percent of these cases.

The challenge in developing gene therapy for the inner ear isn’t a lack of known genes associated with hearing loss, but a lack of vectors to deliver DNA into cells. Brigande, associate professor of otolaryngology and cell, developmental, and cancer biology at the OHSU School of Medicine, provides perspective on companion studies that demonstrate adeno-associated viral vectors as a potent gene transfer agent for cochlear cell targets.

The first study demonstrates safe and efficient gene transfer to hair cells of the mouse inner ear using a synthetic adeno-associated viral vector that promises to be a powerful starting point for developing appropriate vectors for use in the human inner ear. The second study demonstrates that a single neonatal treatment with this viral vector successfully delivers a healthy gene to the inner ear to achieve unprecedented recovery of hearing and balance in a mouse model of a disease called Usher syndrome. Individuals with Usher syndrome type 1c are born deaf and with profound balance issues and experience vision loss by early adolescence. The research teams were led by scientists from the Harvard School of Medicine.

Brigande sees these new studies as potentially spurring investment and kickstarting the development of new approaches to correct a diverse set of deafness genes. 

Hearing Restoration Project consortium member John V. Brigande, Ph.D., is a developmental neurobiologist at the Oregon Hearing Research Center. He also teaches in the Neuroscience Graduate Program and in the Program in Molecular and Cellular Biology at the Oregon Health & Science University. This blog was reposted with the permission of Oregon Health & Science University.

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