ERG

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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New Clues to Sound Localization Issues in Fragile X Syndrome

By Pranav Parikh, Kathleen Wallace, and Elizabeth McCullagh, Ph.D.

Fragile X syndrome (FXS), the most common genetic form of autism, is characterized by impaired cognition, hyperactivity, seizures, attention deficits, and hypersensitivity to sensory stimuli, specifically auditory stimuli.

Individuals with FXS also experience difficulty with determining the source of a sound, known as sound localization. Sound localization is essential for listening in the presence of background noise such as a noisy classroom. The ability to localize sound properly is due to precise excitatory and inhibitory inputs to areas of the brain. 2016 Emerging Research Grants recipient Elizabeth McCullagh, Ph.D., and colleagues hypothesize that the auditory symptoms seen in FXS, specifically issues with sound localization, are due to an overall imbalance of excitatory and inhibitory synaptic input in these brain areas.

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Investigators compared number and size of synaptic structures in different areas of the brainstem responsible for sound localization for several inhibitory neurotransmitters (glycine and GABA) and the primary excitatory neurotransmitter (glutamate) in a mouse model of FXS with a control group. The areas of the brainstem responsible for sound localization are connected to one another in a frequency-specific manner, with low frequency sounds stimulating similar areas and the same for high frequency. It was found that most areas of the brainstem examined did not have changes in number or size of structures, but one area—the medial nucleus of the trapezoid body (MNTB)—had alterations to inhibitory inputs that were specific to the frequency encoded by that region. Glycinergic inhibition was decreased in the high frequency region of MNTB, while GABAergic inhibition was decreased in the low frequency region.

The study by McCullagh and team in The Journal of Comparative Neurology is the first to explore alterations in glycinergic inhibition in the auditory brainstem of FXS mice. Due to the well-characterized functional roles of excitatory and inhibitory neurotransmitters in the auditory brainstem, the sound localization pathway is an ideal circuit to measure the sensory alterations of FXS. Given the findings in this study, further knowledge of the alterations in the lower auditory areas, such as the tonotopic differences in inhibition to the MNTB, may be necessary to better understand the altered sound processing found in those with FXS.

Elizabeth McCullagh, Ph.D., was a 2016 Emerging Research Grants scientist and a General Grand Chapter Royal Arch Masons International award recipient. For more, see Tonotopic alterations in inhibitory input to the medial nucleus of the trapezoid body in a mouse model of Fragile X syndrome” in The Journal of Comparative Neurology.

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 Study Suggests Serotonin May Worsen Tinnitus

By Erik Robinson

Millions of people suffer from the constant sensation of ringing or buzzing in the ears known as tinnitus, creating constant irritation for some and severe anxiety for others. New research by scientists at OHSU shows why a common antidepressant medication may actually worsen the condition.

The study, published Aug. 22 in the journal Cell Reports, focused on the action of serotonin, an important neuromodulator in the brain. Researchers examined brain tissue in mice, specifically the dorsal cochlear nucleus where sensory integration occurs and tinnitus is believed to develop. Researchers discovered that neurons known as fusiform cells within this portion of the brain become hyperactive and hypersensitive to stimuli when exposed to serotonin.

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“We saw that the activity of those neurons went through the roof,” said senior author Laurence Trussell, Ph.D., a professor of otolaryngology in the OHSU School of Medicine and scientist in the Vollum Institute.

The study could have implications for a common class of antidepressants known as selective serotonin reuptake inhibitors. SSRIs can alleviate symptoms of moderate to severe depression and anxiety by increasing the level of serotonin in the brain. Serotonin is a chemical compound that acts as a neurotransmitter thought to be responsible for maintaining mood balance.

However, the new research suggests that SSRIs prescribed to treat anxiety or depression may worsen patients’ tinnitus. Tinnitus is defined as the chronic perception of sound when there is no internal or external acoustic source.

“If you’re a physician treating a patient with hearing loss or tinnitus, you may want to be careful about prescribing a drug that compounds their feelings of anxiety,” said Trussell, who also suffers from tinnitus and has an appointment in the Oregon Hearing Research Center at OHSU. “The SSRI may be enhancing the thing you’re trying to fix.”

Lead author Zheng-Quan Tang, Ph.D., a senior postdoctoral fellow in Trussell’s lab, noted that a review of existing scientific literature indicated that many patients reported an increase in tinnitus soon after they began taking SSRIs.

“Estimates vary, but at least 10 percent of the U.S. population is affected by tinnitus,” Tang said.

The OHSU scientists are interested in exploring another area of research focused on a type of ion channel in the membrane of neurons that is activated by serotonin. If the scientists can determine a way to deactivate those channels, they may be able to allow the beneficial effects of antidepressants while limiting the severity of tinnitus.

The study was supported by the Hearing Health Foundation and National Institutes of Health grants NS028901 and DC004450.

This research synopsis was republished with permission from the Oregon Health & Science University

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