ERG

New Research Shows Hearing Aids Improve Brain Function and Memory in Older Adults

By University of Maryland Department of Hearing and Speech Sciences

One of the most prevalent health conditions among older adults, age-related hearing loss, can lead to cognitive decline, social isolation and depression. However, new research from the University of Maryland (UMD) Department of Hearing and Speech Sciences (HESP) shows that the use of hearing aids not only restores the capacity to hear, but can improve brain function and working memory.

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The UMD-led research team monitored a group of first-time hearing aid users with mild-to-moderate hearing loss over a period of six months. The researchers used a variety of behavioral and cognitive tests designed to assess participants’ hearing as well as their working memory, attention and processing speed. They also measured electrical activity produced in response to speech sounds in the auditory cortex and midbrain.

At the end of the six months, participants showed improved memory, improved neural speech processing, and greater ease of listening as a result of the hearing aid use. Findings from the study were published recently in Clinical Neurophysiology and Neuropsychologia.

“Our results suggest that the benefits of auditory rehabilitation through the use of hearing aids may extend beyond better hearing and could include improved working memory and auditory brain function,” says HESP Assistant Professor Samira Anderson, Ph.D., who led the research team. “In effect, hearing aids can actually help reverse several of the major problems with communication that are common as we get older.”

According to the National Institutes of Health, as many as 28.8 million Americans could benefit from wearing hearing aids, but less than a third of that population actually uses them. Several barriers prevent more widespread use of hearing aids—namely, their high cost and the fact that many people find it difficult to adjust to wearing them. A growing body of evidence has demonstrated a link between hearing loss and cognitive decline in older adults. Aging and hearing loss can also lead to changes in the brain’s ability to efficiently process speech, leading to decreased ability to understand what others are saying, especially in noisy backgrounds.

The UMD researchers say the results of their study provide hope that hearing aid use can at least partially restore deficits in cognitive function and auditory brain function in older adults.

“We hope our findings underscore the need to not only make hearing aids more accessible and affordable for older adults, but also to improve fitting procedures to ensure that people continue to wear them and benefit from them,” Anderson says.

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The research team is working on developing better procedures for fitting people with hearing aids for the first time. The study was funded by Hearing Health Foundation and the National Institutes of Health (NIDCD R21DC015843).

This is republished with permission from the University of Maryland’s press office. Samira Anderson, Au.D., Ph.D., is a 2014 Emerging Research Grants (ERG) researcher generously funded by the General Grand Chapter Royal Arch Masons International. We thank the Royal Arch Masons for their ongoing support of research in the area of central auditory processing disorder. These two new published papers and an earlier paper by Anderson all stemmed from Anderson’s ERG project.

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Read more about Anderson in Meet the Researcher and “A Closer Look,” in the Winter 2014 issue of Hearing Health.

WE NEED YOUR HELP IN FUNDING THE EXCITING WORK OF HEARING AND BALANCE SCIENTISTS. DONATE TODAY TO HEARING HEALTH FOUNDATION AND SUPPORT GROUNDBREAKING RESEARCH: HHF.ORG/DONATE.

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Sound Processing in Early Brain Regions

By Yishane Lee    

Standard hearing tests may not account for the difficulty some individuals have understanding speech, especially in noisy environments, even though the sounds are loud enough to hear. To better identify and treat these central auditory processing disorders that appear despite normal ear function, 2016 Emerging Research Grants (ERG) scientist Richard A. Felix II, Ph.D., and colleagues have been investigating how the brain processes complex sounds such as speech.

In the past, speech processing research has focused on higher-level brain regions like the auditory cortex, but there is strong evidence showing that lower-level subcortical areas may play a significant role in hearing disorders. In their paper “Subcortical Pathways: Toward a Better Understanding of Auditory Disorders,” published online in the journal Hearing Research on Jan. 31, 2018, Felix and team review studies that examine the auditory brainstem and midbrain and their functional effect on hearing ability.

The illustration shows the major inhibitory and excitatory, ascending and descending, neurotransmitter connections of subcortical pathways. The table lists features of auditory processing, with the contribution (or potential impairment) of each structure depicted with increasing strength represented by darker colors.

The illustration shows the major inhibitory and excitatory, ascending and descending, neurotransmitter connections of subcortical pathways. The table lists features of auditory processing, with the contribution (or potential impairment) of each structure depicted with increasing strength represented by darker colors.

Speech contains various acoustic hallmarks such as pitch, timbre, and gaps between starts and stops of sound energy that the brain uses to create distinct auditory “objects”—for example, listening to one voice among multiple talkers in a noisy room. Our brains extract these acoustic clues by decoding spectral, temporal, and spatial information in order to identify and understand complex sounds.

Studies of mammalian species show that these sound features are extracted at the level of the midbrain by nerve cells in a region called the inferior colliculus, and through the integration of multiple ascending (“bottom-up”) pathways: from inner ear hair cells to the auditory nerve; to the brainstem’s cochlear nucleus and superior olivary complex; to the midbrain’s inferior colliculus; to the forebrain’s thalamus; and to the auditory cortex.

For instance, several key functions of auditory processing previously attributed to the cortex, such as the selectivity of neurons to particular vocalizations, are now demonstrated in subcortical pathways. The cortex builds upon these coding strategies to produce typical hearing and communication abilities in most individuals.

Felix and team go on to detail auditory disorders that may result in large part from subcortical processing failures. Since neurotransmitters are important in the brain, including subcortical regions, an imbalance in these chemicals’ excitatory or inhibitory actions (as typically happens with age) can affect the ability to hear complex sounds.

Disruptions of bottom-up processing may lead to hearing difficulties that are not revealed using standard hearing tests. This includes auditory synaptopathy and auditory neuropathy (terms sometimes used interchangeably), also called “hidden hearing loss.” One concern with hidden hearing loss is that subcortical processing may be affected by noise levels previously thought to be relatively safe (as low as 80 decibels).

Likewise, central auditory processing disorders may be a result of abnormal top-down processing, leading to problems with selective attention and other hearing-related tasks.

The authors conclude, “Subcortical pathways represent early-stage processing on which sound perception is built; therefore problems with understanding complex sounds such as speech often have neural correlates of dysfunction in the auditory brainstem, midbrain, and thalamus.” The hope is that further study of animal models as well as human subjects will lead to tools to aid in the diagnosis and treatment of hearing disorders caused by problems with subcortical sound processing.

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Richard A. Felix II, Ph.D., is a postdoctoral researcher in the Hearing and Communications Lab at Washington State University Vancouver. A 2016 Emerging Research Grants recipient, he was generously funded by the General Grand Chapter Royal Masons International. Read more about Felix in “Meet the Researcher,” in the Summer 2017 issue of Hearing Health.


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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New Data-Driven Analysis Procedure for Diagnostic Hearing Test

By Carol Stoll

Stimulus frequency otoacoustic emissions (SFOAEs) are sounds generated by the inner ear in response to a pure-tone stimulus. Hearing tests that measure SFOAEs are noninvasive and effective for those who are unable to participate, such as infants and young children. They also give valuable insight into cochlear function and can be used to diagnose specific types and causes of hearing loss. Though interpreting SFOAEs is simpler than other types of emissions, it is difficult to extract the SFOAEs from the same-frequency stimulus and from background noise caused by patient movement and microphone slippage in the ear canal.

2014 Emerging Research Grants (ERG) recipient Srikanta Mishra, Ph.D., and colleagues have addressed SFOAE analysis issues by developing an efficient data-driven analysis procedure. Their new method considers and rejects irrelevant background noise such as breathing, yawning, and subtle movements of the subject and/or microphone cable. The researchers used their new analysis procedure to characterize the standard features of SFOAEs in typical-hearing young adults and published their results in Hearing Research.

Mishra and team chose 50 typical-hearing young adults to participate in their study. Instead of using a discrete-tone procedure that measures SFOAEs one frequency at a time, they used a more efficient method: a single sweep-tone stimulus that seamlessly changes frequencies from 500 to 4,000 Hz, and vice versa, over 16 and 24 seconds. The sweep tones were interspersed with suppressor tones that reduce the response to the previous tone. The tester manually paused and restarted the sweep recording when they detected background noises from the subject’s movements.

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The SFOAEs generated were analyzed using a mathematical model called a least square fit (LSF) and a series of algorithms based on statistical analysis of the data. This model objectively minimized the potential error from extraneous noises. Conventional SFOAE features such as level, noise floor, and signal-to-noise ratio (SNR) were described for the typical-hearing subjects.

Overall, the results of this study demonstrate the effectiveness of the automated noise rejection procedure of sweep-tone–evoked SFOAEs in adults. The features of SFOAEs characterized in this study from a large group of typical-hearing young adults should be useful for developing tests for cochlear function that can be useful in the clinic and laboratory.

Srikanta Mishra, Ph.D, was a 2014 Emerging Research Grants scientist and a General Grand Chapter Royal Arch Masons International award recipient. For more, see Sweep-tone evoked stimulus frequency otoacoustic emissions in humans: Development of a noise-rejection algorithm and normative features” in Hearing 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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Improving Diagnostic Test for Ménière’s Disease

By Wafaa Kaf, Ph.D., and Carol Stoll

Electrocochleography (ECochG) is a commonly used assessment of the auditory system, specifically the inner ear and the hearing nerve. ECochG is most often elicited by a brief acoustic stimulus, known as a “click,” at a relatively low repetition rate. It measures two key responses: summating potential (SP) and action potential (AP), which assist in the diagnosis of Ménière’s disease, an inner ear and balance disorder. Previous research has established that individuals with Ménière’s disease are likely to have abnormally large SPs and a large SP/AP ratio. Though click ECochG has great potential to detect Ménière’s disease, it lacks sensitivity, or the ability to correctly identify those with the disease. Only 69% of those with Ménière’s disease are correctly diagnosed, while 31% of those with the disease have normal ECochG results. This lack of accuracy prevents its use as a definitive diagnostic tool. Hearing Health Foundation 2015 Emerging Research Grants recipient, Wafaa Kaf, Ph.D., is researching the use of a novel analysis technique called Continuous Loop Averaging Deconvolution (CLAD) to best improve the sensitivity of ECochG to high click rate for diagnosing Ménière’s disease. Findings were recently published in Ear and Hearing 2017.

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In a recently published paper in Frontiers in Neuroscience, Kaf’s research team shares its findings on the effects of altering the parameters of the acoustic stimulus on ECochG responses to quantify the effect of stimulus rate and duration of the elicited stimuli. Kaf and her research team obtained SP measurements to 500Hz and 2000Hz tone bursts that varied in duration and repetition rate from 20 adult females with normal hearing. CCLAD was used to interpret the tracings elicited by the differing stimuli of tone bursts.

They found that SP amplitude was significantly larger when using the highest stimulus repetition rate. It is believed that the high stimulus repetition rates minimize the neural contributions and mostly reflect hair cell responses, the target of ECochG. In addition, longer duration stimuli is believed to better reflect hair cell involvement while shorter stimuli may be useful in eliciting responses reflective of neural contributions. Lastly, 2000Hz tone bursts produced larger SP amplitude as compared to 500Hz tone bursts. Therefore, 2000Hz tone bursts with a high repetition rate and long duration can be used as parameters to minimize neural contributions to SP measures whereas short duration stimuli can be used if one wishes to asses neural activity.  

The data that Kaf’s team published is a critical initial advancement towards ultimately understanding the SP measurement in diseased ears. Their findings not only provide normative data for tone burst ECochG across stimulus frequencies, stimulus rates, and stimulus durations, but also help others better understand how to improve sensitivity of ECochG for early diagnosis of Ménière’s disease.  

Wafaa Kaf, Ph.D., is a 2015 Emerging Research Grants recipient. Her grant was generously funded by The Estate of Howard F. Schum.

WE NEED YOUR HELP IN FUNDING THE EXCITING WORK OF HEARING AND BALANCE SCIENTISTS. DONATE TODAY TO HEARING HEALTH FOUNDATION AND SUPPORT GROUNDBREAKING RESEARCH: HHF.ORG/DONATE.

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Research Aims to Improve Fit and Increase Use of Hearing Aids in U.S.

By University of Maryland Department of Hearing and Speech Sciences

Photo Credit: Shutterstock

Photo Credit: Shutterstock

Although about 28.8 million Americans could benefit from wearing hearing aids, less than a third of that population actually uses them, according to the National Institutes of Health. While cost is a contributing factor, experts say many people with hearing loss choose not to wear hearing aids simply because they have difficulty adjusting to them. Researchers with the University of Maryland Department of Hearing and Speech Sciences (HESP) are hoping to improve those figures by developing better procedures for fitting people with hearing aids for the first time.

“Right now when someone is fitted with hearing aids, the focus is on increasing audibility of sounds reaching the ear,” says HESP Assistant Professor Samira Anderson, Au.D., Ph.D. “However, in order to actually understand what someone is saying, sound has to travel from the ear up to the brain. We’re interested in understanding how wearing a hearing aid affects that process.”

Dr. Anderson, University of Maryland Department of Hearing and Speech Sciences

Dr. Anderson, University of Maryland Department of Hearing and Speech Sciences

In a study published recently in Ear & Hearing, Anderson and colleagues outfitted 37 older adults with mild to severe hearing loss with new, in-the-ear hearing aids donated by Widex USA. The researchers placed electrodes on the surface of the patients’ skin to measure electrical activity produced in response to sound in the auditory cortex and midbrain. They found that the brain’s processing of sounds improved while wearing hearing aids.

“There’s a growing body of research showing that hearing loss can lead to accelerated cognitive decline and isolation as people age,” Anderson says. “My hope is that we can develop enhanced testing procedures that will allow more people to benefit from hearing aids and enjoy a better quality of life.”

The UMD research team plans to continue evaluating the patients in their study during the first six months of hearing aid use. In future studies, researchers hope to investigate the effects of manipulating hearing aid parameters on neural processing. The study was funded by the UMD Department of Hearing and Speech Sciences, Hearing Health Foundation, and the National Institutes of Health (NIDCD Grant T32DC000046).

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Samira Anderson, Au.D., Ph.D., is a 2014 Emerging Research Grants researcher generously funded by the General Grand Chapter Royal Arch Masons International. We thank the Royal Arch Masons for their ongoing support of research in the area of central auditory processing disorder. Read more about Anderson and her research in “A Closer Look,” in the Winter 2014 issue of Hearing Health.

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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HHF Partner Hyperacusis Research Shares 14-Year-Old’s Heartbreaking Story to Fight Noise Intolerance

Photo Credit: Hyperacusis Research

Photo Credit: Hyperacusis Research

By Lauren McGrath

Hearing Health Foundation (HHF) Emerging Research Grants (ERG) grant funder Hyperacusis Research—a nonprofit dedicated to developing effective treatments for hyperacusis and to funding research that will eliminate the underlying mechanisms that cause hyperacusis—has a new reason to fight to cure the noise intolerance disorder.

Cindy, 14 years old, has suffered from hyperacusis since she was blasted in the face with an airhorn one year ago. The blast almost immediately prompted “a burst of pain in [her] ear” that made it “feel like someone was stabbing [her].” Six months and several doctors’ visits later, an occupational therapist recognized her symptoms and diagnosed her with the disorder, which causes Cindy to experience pain at low levels of sound relative to what a person with typical hearing can withstand.

Once a happy and social eighth-grader, Cindy now rarely leaves her home. Secluded from the painful sounds of the outside world, her house has become “her sanctuary,” her mother explains. Her intolerance of everyday noises like the school cafeteria and teachers’ voices has forced her to leave public school in exchange for an isolating homeschool experience. “The thing I hate most is that I can’t see friends,” Cindy shares.

Cindy suffers from one of four hyperacusis subtypes called pain hyperacusis. The other three types, according to Hyperacusis Research, are loudness hyperacusis (which causes moderately intense sounds to be perceived as very loud), annoyance hyperacusis (which causes negative emotional reactions to sounds), and fear hyperacusis (which prompts an aversive response to sounds that causes anticipatory response and avoidance behavior). Specific medical treatments, at the moment,  do not yet exist for pain hyperacusis.

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Those inspired to help Cindy can donate to Hyperacusis Research to advance the ontological knowledge of hyperacusis through research grants, including those awarded to HHF’s ERG investigators.

Since 2015, Hyperacusis Research has generously funded grants for a total of five ERG investigators focused on hyperacusis at the University at Buffalo, Oregon Health and Science University, and Massachusetts Eye and Ear Infirmary. You can learn more about our ERG researchers’ efforts to better understand the mechanisms, causes, diagnosis, and treatments of hyperacusis and severe forms of loudness intolerance here.

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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Prenatal Intervention May Be Necessary for Usher Syndrome Treatment

By Carol Stoll

Usher syndrome is a hereditary disorder that affects 1 in 20,000 people worldwide and causes concurrent hearing and vision loss. Though currently there is no cure, scientists have begun to understand the molecular mechanisms of hearing loss in Usher syndrome by identifying the specific mutations in genes associated with auditory hair cell malfunction. Gene-specific targeting has been used to target Usher mutations and restore hearing, but the effectiveness and best timing of the treatment is still being investigated in mouse models. Recent research published in JARO by Emerging Research Grants (ERG) recipient Michelle Hastings, Ph.D., and colleagues shows that early administration of a genetic targeting treatment is critically important for repairing outer hair cells and thus rescuing hearing in those with genetic disorders like Usher syndrome.

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Hastings’ research focuses on type 1 Usher, which is the most severe of three subtypes and is associated with six genes. One of these genes, USH1C, contains the instructions to create a protein that localizes to auditory hair cells and helps to maintain their bundle structure and ability to detect sound waves. A mutation in USH1C causes this protein to be cut short and malfunction, and is thus responsible for type 1C Usher in humans. Adding, or “knocking-in,” the mutation to mouse DNA causes symptoms similar to those of human patients with type 1C Usher. These Usher mice exhibit hearing and vision loss as well as deficits in balance, little or no auditory-evoked brainstem response (ABR), and abnormal eye tests called electroretinograms. The hearing loss is linked to defective or missing inner and outer hair cells in the cochlea of the inner ear.

Antisense oligonucleotide (ASO) therapy is a gene-specific targeting therapy previously used by Hastings and her colleagues to rescue hearing in Usher knock-in mice. ASOs are small strands of nucleotides (the building blocks of DNA and RNA) that are specifically synthesized to bind to the disease-causing mutation site of RNA and block it from creating defective RNA and proteins. The ASO therapy targeting the USH1C mutation was administered to the Usher mice a few days after birth. Hearing was rescued and ABR improved, which is indicative of improved inner hair cell function. However, function of the outer hair cells, which surround the inner hair cells and are responsible for amplifying sounds, was not tested.

Hastings’ most recent study, with Jennifer Lentz, Ph.D.’s research group, investigated whether the timing of ASO treatment is important for rescuing outer hair cells in addition to inner hair cells for full hearing rescue. ASO therapy was administered to knock-in Usher mice of varying ages, and then outer hair cell function was tested by measuring distortion product otoacoustic emissions (DPOAEs) in 1-, 3-, and 6-month-old mice. When two tones are presented in the ear canal, outer hair cells that function normally respond by producing amplified sounds known as DPOAEs. In Usher mice, DPOAEs are not detected, which indicates loss of outer hair cell function. ASO treatment was able to recover outer hair cell function measured by DPOAEs when it was administered one day after birth. However, the treatment was not effective if first administered on or after postnatal day five.

The results of this study indicate that there is a developmental window of time when USH1 gene expression is needed to properly develop auditory hair cells, and thus early genetic treatment is essential for hearing rescue of those with Usher syndrome. In humans, hair cell development occurs early in pregnancy, and thus ASO treatment would likely require very early prenatal intervention. ASOs have been approved for clinical use for a number of different diseases in humans, but more animal research is necessary before moving to clinical trials for ASO therapy for Usher syndrome. Hastings has also published research on testing ASO therapy on prenatal mice, and found that injecting ASOs in the amniotic cavity of pregnant mice can in fact access the cochlea. Hastings’ research has improved the scientific community’s understanding of the functions of inner and outer hair cells and brings us closer to developing a cure for Usher syndrome.

Michelle Hastings, Ph.D., was a 2009 and 2011 Emerging Research Grants scientist. For more, see “Rescue of Outer Hair Cells With Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment” in The Journal of the Association for Research in Otolaryngology.

Empower groundbreaking research toward better treatments and cures for Usher syndrome. If you are able, please make a contribution today.

 
 
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The Gap Between Self-Reported Hearing Loss and Treatment Patterns

By Carol Stoll

Hearing loss is one of the most prevalent chronic conditions in the U.S. and has been associated with negative physical, social, cognitive, economic, and emotional consequences. Despite the high prevalence of hearing loss, substantial gaps in the utilization of amplification options, including hearing aids and cochlear implants (CI), have been identified. Harrison Lin, M.D., a 2016 Emerging Research Grants recipient, along with colleagues, recently published a paper in JAMA Otolaryngology–Head & Neck Surgery that investigates the contemporary prevalence, characteristics, and patterns of specialty referral, evaluation, and treatment of hearing difficulty among adults in the U.S.

Unlike this man who is having his hearing tested, a large number of individuals in the U.S. who experience hearing difficulties are not seeking treatment. Photo source:    Bundesinnung Hörakustiker, Flickr.

Unlike this man who is having his hearing tested, a large number of individuals in the U.S. who experience hearing difficulties are not seeking treatment. Photo source: Bundesinnung Hörakustiker, Flickr.

The researchers did a cross-sectional analysis of responses from a nationwide representative sample of adults who participated in the 2014 National Health Interview Survey and responded to hearing health questions. The data collected included demographic information as well as self-reported hearing status, functional hearing, laterality (hearing ability in each ear), onset, and primary cause (if known) of the hearing loss. In addition, the team analyzed specific data regarding hearing-related clinician visits, hearing tests, referrals to hearing specialist, and utilization of hearing aids and CIs.

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Overall, 36,690 records were included in the analysis, which extrapolated to an estimated 239.6 million adults in the U.S. Nearly 17 percent indicated their hearing was less than “excellent/good,” ranging from “a little trouble hearing” to “deaf.” Approximately 21 percent of respondents had visited a physician for hearing problems in the preceding five years. Of these, 33 percent were referred to an otolaryngologist and 27 percent were referred to an audiologist. Of the adults who indicated their hearing from “a little trouble hearing” to being “deaf,” 32 percent had never seen a clinician for hearing problems and 28 percent had never had their hearing tested.

The study shows that there are considerable gaps between self-reported hearing loss and patients receiving medical evaluation and recommended treatments for hearing loss. Increased awareness among clinicians regarding the burden of hearing loss, the importance of early detection and medically evaluating hearing loss, and available amplification and CI options can contribute to improved care for individuals with hearing difficulty. Future studies are warranted to further investigate the observed trends of this study.

Harrison W. Lin, M.D., is a 2016 Emerging Research Grants recipient. His grant was generously funded by funded by The Barbara Epstein Foundation, Inc.

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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Cellular Changes and Ménière’s Disease Symptoms

By Carol Stoll

Ménière’s disease is characterized by fluctuating hearing loss, vertigo, tinnitus, and ear fullness, but the causes of these symptoms are not well understood. Past research has suggested that a damaged blood labyrinthine barrier (BLB) in the inner ear may be involved in the pathophysiology of inner ear disorders. Hearing Health Foundation (HHF)’s 2016 Emerging Research Grants (ERG) recipient Gail Ishiyama, M.D., was the first to test this proposition by using electron microscopy to analyze the BLB in both typical and Ménière’s disease patients. Ishiyama’s research was fully funded by HHF and was recently published in Nature publishing group, Scientific Reports.

The BLB in a Meniere’s disease capillary. a) Capillary located in the stroma of the macula utricle from a Meniere’s subject (55-year-old-male). The lumen (lu) of the capillary is narrow, vascular endothelial cells (  vec  ) are swollen and the cytoplasm is vacuolated (pink asterisks). b. Diagram showing the alterations in the swollen   vec  , microvacuoles are also abundant (v). Abbreviations,   rbc  : red blood cells,   tj  : tight junctions, m: mitochondria, n: cell nucleus, pp: pericyte process;   pvbm  : perivascular basement membrane.   Bar   is 2 microns.

The BLB in a Meniere’s disease capillary. a) Capillary located in the stroma of the macula utricle from a Meniere’s subject (55-year-old-male). The lumen (lu) of the capillary is narrow, vascular endothelial cells (vec) are swollen and the cytoplasm is vacuolated (pink asterisks). b. Diagram showing the alterations in the swollen vec, microvacuoles are also abundant (v). Abbreviations, rbc: red blood cells, tj: tight junctions, m: mitochondria, n: cell nucleus, pp: pericyte process; pvbm: perivascular basement membrane. Bar is 2 microns.

The BLB is composed of a network of vascular endothelial cells (VECs) that line all capillaries in the inner ear organs to separate the vasculature (blood vessels) from the inner ear fluids. A critical function of the BLB is to maintain proper composition and levels of inner ear fluid via selective permeability. However, the inner ear fluid space in patients with Ménière’s has been shown to be ballooned out due to excess fluid. Additionally, the group had identified permeability changes in magnetic resonance imaging studies of Meniere’s patients, which may be an indication of BLB malfunction.

Ishiyama’s research team used transmission electron microscopy (TEM) to investigate the fine cellular structure of the BLB in the utricle, a balance-regulating organ of the inner ear. Two utricles were taken by autopsy from individuals with no vestibular or auditory disease. Five utricles were surgically extracted from patients with severe stage IV Ménière’s disease with profound hearing loss and intractable recurrent vertigo spells, who were undergoing surgery as curative treatment.

Microscopic examination revealed significant structural differences of the BLB within the utricle between individuals with and without Ménière’s disease. In the normal utricle samples, the VECs of the BLB contained numerous mitochondria and very few fluid-containing organelles called vesicles and vacuoles. The cells were connected by tight junctions to form a smooth, continuous lining, and were surrounded by a uniform membrane.

However, samples with confirmed Ménière’s disease showed varying degrees of structural changes within the VECs; while the VECs remained connected by tight junctions, an increased number of vesicles and vacuoles was found, which may cause swelling and degeneration of other organelles. In the most severe case, there was complete VEC necrosis, or cell death, and a severe thickening of the basal membrane surrounding the VECs.

The documentation of the cellular changes in the utricle of Ménière’s patients was the first of its kind and has important implications for future treatments. Ishiyama’s study concluded that the alteration and degeneration of the BLB likely contributes to fluid changes in the inner ear organs that regulate hearing and balance, thus causing the Ménière’s symptoms. Further scientific understanding of the specific cellular and molecular components affected by Ménière’s can lead to the development of new drug therapies that target the BLB to decrease vascular damage in the inner ear.

Gail Ishiyama, M.D., is a 2016 Emerging Research Grants recipient. Her grant was generously funded by The Estate of Howard F. Schum.

WE NEED YOUR HELP IN FUNDING THE EXCITING WORK OF HEARING AND BALANCE SCIENTISTS. DONATE TODAY TO HEARING HEALTH FOUNDATION AND SUPPORT GROUNDBREAKING RESEARCH: HHF.ORG/DONATE.

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Gaining Better Clarity of Neural Networks

By Pranav Parikh

The ear, just like any other organ in the human body, uses nerves to function properly. One of the most vital nerves that the ear uses is the cochlear nerve, which connects the inner ear to the brain, or more specifically to the tonotopically-based regions of the cochlear nuclear complex located in the brainstem. This nerve shares the same shape and design of most nerves in the body, with dendrites absorbing information from various sources, sending the signal down the axon of the nerve through action potentials, and terminating the signal in a synapse so the message can be spread. In order to allow for this process to occur expediently, the nerve encounters a process known as myelination (providing a myelin sheath to propagate a signal faster). This is done through a glial cell known as an oligodendrocyte. Oligodendrocytes form a layer of lipid (fat) and protein around the axon to provide insulation, thereby allowing for signals to be sent to the brain more efficiently.

The immunoreactivity of Olig2 was detected during postnatal day (PND) 0 to 7, which became weaker after PND 10. Before PND 7, the majority of Olig2-expressing cells were found within the modiolus at the basal cochlear turn, while a few cells were located peripherally to the DIC-PCTZ and in close proximity to the spiral lamina at the basal cochlea turn. After PND 7, Olig2-expressing cells were fully overlapped with the DIC-PCTZ within modiolus at the spiral lamina in the basal cochlea.

The immunoreactivity of Olig2 was detected during postnatal day (PND) 0 to 7, which became weaker after PND 10. Before PND 7, the majority of Olig2-expressing cells were found within the modiolus at the basal cochlear turn, while a few cells were located peripherally to the DIC-PCTZ and in close proximity to the spiral lamina at the basal cochlea turn. After PND 7, Olig2-expressing cells were fully overlapped with the DIC-PCTZ within modiolus at the spiral lamina in the basal cochlea.

A team of scientists led by Dr. Zhengqing Hu, funded by Hearing Health Foundation through its Emerging Research Grants program (2010 & 2011) was able to analyze oligodendrocyte protein expression in the cochlear nerve of postnatal mice. Through the use of Differential Interference Contrast (DIC) microscopy, they were able to investigate the cochlear nerve at staggered postnatal days, meaning the period following birth.

Their findings indicate oligodendrocytes are found to migrate along with the transition zone between the central and peripheral nervous systems. As the fetus develops after birth, and myelination occurs in the nerves connecting to the brain, the oligodendrocyte protein marker Oligo2 was observed. This could mean loss of hearing function could be connected to unmyelinated axons. There are many other neurodegenerative autoimmune diseases, such as multiple sclerosis, caused by demyelination, and hearing loss could potentially be added to that list. Dr. Hu’s work improves clarity of the neural network connecting the inner ear and the brain.

Zhengqing Hu, M.D., Ph.D. , is a 2010 and 2011 Emerging Research Grants recipient. Hu's research was published by Otolaryngology-Head and Neck Surgery on July 11, 2017.

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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