Estrogen’s Role in Hearing and Protecting Against Hearing Loss

By Christopher Geissler, Ph.D.

While the anatomy of the inner ear does not vary much among individuals, differences in hearing and hearing loss in men and women are well documented. A recent review of these differences by Benjamin Z. Shuster, Didier A. Depireux, Ph.D., Jessica A. Mong, Ph.D., and Ronna Hertzano, M.D., Ph.D., a member of the Hearing Health Foundation’s Hearing Restoration Project, appeared in the June 2019 issue of the Journal of the Acoustical Society of America. 

Surveying the existing literature, the authors summarize what is known about estrogen’s role in protecting against or lessening the effects of hearing loss. Estrogen is a hormone present in all human beings but in higher levels generally in individuals who identify as female. 

Documented sex differences include better outer hair cell function and more prominent auditory brainstem response in women. Women also have lower rates of hearing loss than men, and men also experience declines in hearing more rapidly than their female counterparts. 

There is substantial evidence that estrogen plays a role in these differences, which is unsurprising, given that sex hormones are often behind physiological differences between the sexes. Studies demonstrate that estrogen helps determine hearing ability and can protect hearing over time. 

But despite ample evidence of estrogen’s role in hearing, scientists are still not entirely sure how it works. Further research on estrogen and hearing will help scientists develop treatments for age-related and noise-induced hearing loss. 

A better understanding of estrogen’s role in hearing and differences between the sexes is also important because, as the authors point out, “a large sex bias still exists in many aspects of hearing research,” which means that studies that involve only men or that do not account for sex at all could lead to the development of treatments that will be less effective for women.

Christopher Geissler, Ph.D. is Hearing Health Foundation (HHF)’s director of program and research support. Ronna Hertzano, M.D., Ph.D., is a member of HHF’s Hearing Restoration Project consortium based at University of Maryland School of Medicine.

A Newly Identified Neuron in a Brain Region Tied to Hearing

By Michael T. Roberts, Ph.D.

Most of our auditory experience requires extensive and precise computations in the brain. While the neural circuitry underlying these computations has become increasingly clear over the past several decades, there has remained a big gap in our understanding of the neural circuitry in an important brain region called the inferior colliculus (IC).

Located in the midbrain, the IC is the hub of the brain’s auditory pathway. Like an airport hub that processes travelers moving among farflung airports, the IC receives and processes most of the output of lower auditory centers and provides the major source of auditory input to higher brain centers.

Although the IC plays important roles in most auditory functions, including speech processing and sound localization, it has proven difficult to identify the types of neurons (nerve cells) that make up the IC. This has hampered progress because the ability to identify neuron types is a prerequisite for determining how specific neurons interconnect and function within the broader auditory circuitry.

Recently, my lab at the University of Michigan tackled this long-standing problem and successfully identified a novel neuron type called VIP neurons. VIP neurons make a small protein called vasoactive intestinal peptide. Despite its name, previous studies have shown that VIP is made by specific types of neurons in several other brain regions.

Sections of the inferior colliculus, the hub of the brain’s auditory pathway. A newly identified neuron type called VIP neurons, which make a small protein called vasoactive intestinal peptide, have been dyed magenta.

Our team, led by postdoctoral fellow David Goyer, Ph.D., hypothesized that VIP is a marker for a class of neurons in the IC. To test this hypothesis, we used a genetically engineered mouse to label VIP neurons with a red fluorescent protein. This made it possible to use fluorescence microscopy to target experiments to VIP neurons in the IC.

These experiments revealed that VIP neurons in the IC have internally consistent anatomical and physiological features, supporting the conclusion that IC VIP neurons constitute a distinct neuron type. Examination of the neuronal processes of VIP neurons further revealed that individual VIP neurons likely receive input from a range of sound frequencies. Work by collaborators in the Schofield Lab at Northeast Ohio Medical University showed that VIP neurons also send output to several brain regions, including to higher and lower auditory centers and to a brain region involved in visual processing.

In another set of experiments, we combined electrical recordings from VIP neurons with a technique called optogenetics, which allows scientists to stimulate specific populations of neurons using brief flashes of light. These experiments revealed that VIP neurons receive input from the dorsal cochlear nucleus, one of the first brain regions in the auditory pathway. The path from the cochlea to VIP neurons is therefore quite short, passing through only three synapses.

This study, which combined both sets of experiments and was published in eLife on April 18, 2019, showed that VIP neurons are a distinct and readily identifiable class of IC neurons. Based on their features, we hypothesize that VIP neurons play a broadly influential role in sound processing. We and the Schofield lab are currently testing this hypothesis, with a particular emphasis on determining how VIP neurons contribute to speech processing in the IC. 

A 2017 Emerging Research Grants scientist, Michael T. Roberts, Ph.D., heads the Roberts Laboratory and is an assistant professor at the Kresge Hearing Research Institute, University of Michigan.

CT Imaging as a Diagnostic Tool for Ménière’s Disease

By Ngoc-Nhi Luu, M.D., Dr. med.

Ménière’s disease is an inner ear condition with symptoms including vertigo, hearing loss, and tinnitus, and may be associated with an accumulation of fluid in the inner ear, termed endolymphatic hydrops. Diagnosis of Ménière’s is entirely based on clinical characteristics, and to date, no classification has been established that can predict the onset or course of the disease. Patients with Ménière’s can have varying degrees of symptoms, so defining subtypes within the Ménière’s population may help establish a classification to improve diagnoses and treatments.

Our previous analysis of cadaveric ears of patients with Ménière’s revealed striking differences within the endolymphatic sac in the inner ear, which regulates endolymph fluid. We had found two different aberrations of the endolymphatic sac—its underdevelopment or its degeneration—among Ménière’s patients, suggesting that the loss of endolymphatic sac cell function and the possible impairment of endolymphatic fluid regulation may lead to Ménière’s. In addition, these two pathologies may be associated with differing clinical traits of the disease.

In our prior work, we examined sections of human cadaveric inner ears with Ménière’s and found differences in the angular trajectory of the vestibular aqueduct (ATVA), the bony canal in which the endolymphatic sac is located. These differences resembled either the trajectory of typical adults, or the trajectory of early developmental, fetal vestibular aqueducts. ATVA similar to other adults without Ménière’s were associated with late onset of the condition, whereas Ménière’s patients with “fetal” ATVA experienced early onset.

A 3D reconstruction of the endolymphatic space of a typical human adult inner ear. In Ménière’s disease patients, the anatomy of the endolymphatic sac differs, suggesting that the impairment of the sac’s function to regulate fluid may lead to Ménière’s. (LSC, lateral semicircular canal; PSC, posterior semicircular canal; SCC, superior semicircular canal.)

For our paper published in the journal Otology & Neurotology in April 2019, we hypothesized that this difference can be detected with a CT scan (computerized tomography) in patients with early or late onset Ménière’s.

We used a custom-made, open-source web application for angle measurements and applied this technique on high resolution CT imaging of patients with Ménière’s. Comparing the angle measurements of the ATVA, we confirmed the results of the cadaveric study. There was a strong correlation between late onset Ménière’s with a typical “adult” course of the vestibular aqueduct, while early onset Ménière’s was associated with a more straight, “fetal” course of the vestibular aqueduct.

As such our study aims to develop a radiographic screening tool, such as a CT scan of the inner ear, to classify different Ménière’s subtypes. It appears that early onset Ménière’s patients have a different anatomy of the vestibular aqueduct compared with late onset Ménière’s patients.

We want to better understand if these findings also correlate with additional clinical factors, such as specific symptoms or a positive family history for Ménière’s. Ultimately, this may help to further characterize different Ménière’s subtypes in order to better diagnose, predict the course of, and treat the condition.

Ngoc-Nhi Luu, M.D., Dr. med., is a postdoctoral fellow at Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Harvard Medical School, and an ENT resident at University Hospital Zurich. Luu’s 2017 ERG grant was generously funded by The Estate of Howard F. Schum. Coauthors on the paper include Judith Kempfle, M.D. (a 2010 ERG scientist), Steven Rauch, M.D. (1990 ERG), and Joseph Nadol, M.D. (1976–77 ERG).

Lasting Effects From Head and Brain Injury

By Elliott Kozin, M.D.

Traumatic brain injury (TBI) is a major public health issue and contributes to injury-related morbidity and mortality worldwide. The estimated economic cost of TBI is estimated to be in excess of $76 billion per year in the United States. Unfortunately, the health effects of TBI are profound. TBI can lead to chronic and debilitating physical and psychosocial symptoms, such as loss of cognitive, sensory, and psychological function. Auditory and vestibular dysfunction has long been recognized as a consequence of head injury, including TBI. 

In our research “Patient‐Reported Auditory Handicap Measures Following Mild Traumatic Brain Injury,” published in The Laryngoscope, we examined auditory complaints following traumatic brain injury, as well as changes that occur to the peripheral vestibular system in the postmortem setting. In patients with mild traumatic brain injury (mTBI), we used patient-reported outcome measures to assess auditory complaints. The team found that auditory symptoms and associated handicap were common in patients with non-blast mTBI. 

For another paper in The Laryngoscope, “Peripheral Vestibular Organ Degeneration After Temporal Bone Fracture: A Human Otopathology Study,” we evaluated postmortem specimens from the National Temporal Bone Pathology Registry with head injury. In a cohort of patients with temporal bone fractures, there were distinct peripheral vestibular changes. Collectively, these findings have implications for the pathophysiology and management of symptoms in this patient population.

Elliott Kozin, M.D., is a neurotology fellow at Eaton Peabody Laboratories, Massachusetts Eye and Ear/Harvard Medical School, and a 2018 Emerging Research Grants recipient generously funded by the General Grand Chapter Royal Arch Masons International.

Making Sense of Sound

Rush College of Health Sciences

In most auditory testing, the emphasis is on accuracy in speech recognition, since speech is our primary means of communication. But myriad sounds beyond language are key to our understanding of the world around us.

“A car honking, a baby crying, a fire alarm — recognizing these sounds can be important to our safety,” explained Valeriy Shafiro, Ph.D. “And there are also lots of nonlinguistic environmental sounds we enjoy listening to: the sound of the ocean, the wind in the trees when we walk in the woods.” Shafiro, an associate professor of communication disorders and principal investigator in the Rush Auditory Research Laboratory, conducts research in hearing and speech perception that focuses on finding new ways to diagnose auditory deficits and improve communication abilities in adults. These new diagnostic techniques have the potential to improve the quality of life of a variety of audiology patients — even well beyond the groups Shafiro is currently studying.

Addressing a rehab deficit 

Much of Shafiro’s lab’s past work, which has been funded by the National Institutes of Health (NIH), the American Speech-Language-Hearing Foundation (ASHFoundation) and the Hearing Health Foundation, formerly known as the Deafness Research Foundation, has assessed the ability of people with cochlear implants to recognize a variety of nonspeech sounds — a particularly useful means of auditory assessment in a large, urban medical center that treats many non-English speakers.

A recent study tested listeners’ ability to recognize those sounds with or without the contextual clues present in everyday life. For example, an ambiguous sound can be perceived as a burning fuse when preceded by the sound of a match being struck and followed by the sound of an explosion, but it may be perceived as bacon frying when surrounded by other kitchen sounds.

Credit: Rush University

“Compared with people with normal hearing, people with cochlear implants show some pretty clear deficits in identifying environmental sounds as well as speech,” Shafiro said. “Research from several labs, including ours, shows the possibility for cochlear implant users to improve if they work on it. But there are few readily available opportunities for these patients to obtain rehabilitation, for reasons including travel difficulties, health care reimbursements and scope of practice.”

Shafiro is now evaluating the usefulness of Internet-based environmental sound and speech training for people who rely on cochlear implants in daily life. “A Randomized Controlled Trial to Evaluate the Benefits of an Internet-Based Auditory Training Program for Cochlear Implant Patients,” a two-year grant from the ASHFoundation, aims to help fill the rehabilitation deficit for adults who receive cochlear implants.

“With Internet access now widely available, patients can do the auditory exercises online, at their own pace and without having to travel,” Shafiro said. When completed, the study will give him and his colleagues a deeper understanding of the benefits and challenges of computerized auditory training.

Hearing-dementia link

Measuring listeners’ recognition of nonlinguistic sounds was also a component of a recent study from the Rush Auditory Research Laboratory in collaboration with the Rush Alzheimer’s Disease Center.

“Hearing, Speech and Episodic Memory in Older African-American and White Adults,” funded with a grant from the NIH, examined a topic of wide current interest: the relationship between aging, hearing loss and cognitive deficits. As Baby Boomers age, research like this has major implications for the health and well-being of older adults. “Some recent research has reported that people with a greater rate of age-related hearing loss also have a greater rate of cognitive decline,” Shafiro explained.

“Typical tests of working memory are based on retaining words or numbers, but we wanted to explore this further by measuring both nonspeech and speech perception.” 

Using tests previously designed by Stanley Sheft, senior researcher at the Rush Auditory Research Laboratory and principal investigator on the study, the team measured the ability of a cohort of community-dwelling older adults without known dementia to discriminate brief nonlinguistic sound patterns.

The addition of nonlinguistic sounds produced somewhat different results than those yielded by previous research. Although other studies have associated speech perception with cognitive performance, the Rush study did not find this correlation when measuring hearing thresholds or the ability to recognize speech in noise.

However, “We found a relationship between working memory and the ability to discriminate brief auditory patterns,” said Shafiro, who hopes to revisit the study cohort in the future to see whether the tests may be predictive of the trajectory of cognitive decline.

This article was repurposed with permission from Rush University Medical Center, and originally appeared in the Rush College of Health Sciences magazine Impact. Valeriy Shafiro, Ph.D., is a 2008 Emerging Research Grants recipient.

Moving Beyond Wnt and Notch Pathways for Hair Cell Regeneration

By Christopher Geissler, Ph.D.

There are several active human clinical trials evaluating the safety of inner ear hair cell regeneration therapies, but these therapies’ target mechanisms may be insufficient to stimulate hair cell growth in the adult mammalian cochlea. These approaches rely on the canonical Wnt and Notch signaling pathways and the Atoh1 molecule, which is necessary for hair cell regeneration and is regulated by these pathways. 

However, a report published in Molecular Therapy in May 2019 by Anshula Samarajeewa, Bonnie E. Jacques, Ph.D., and Alain Dabdoub, Ph.D., a member of Hearing Health Foundation (HHF)’s Hearing Restoration Project (HRP) consortium, notes that there has been very limited success thus far in regenerating hair cells in adult mammalian cochlea using these signaling pathways. This likely means, the authors write, that researchers will need combined approaches that also use epigenome-editing techniques to address changes to the genetic material and activity that occurs with age. 

Both the Wnt and Notch pathways play a role in determining how inner ear cells develop into specific types of cells and multiply, and they are also important in the development of the cochlea as a whole. Activating Wnt pathways and inhibiting Notch pathways can turn supporting cells into hair cells in fetuses and newborn mammals, making these key targets for hair cell regeneration. But both become much less effective as the body ages. Manipulating these pathways in adult animals has led to some success in regenerating hair cells, but these new hair cells tend not to develop fully, do not form necessary connections with auditory neurons, or even survive.  

This lack of success is not because these pathways no longer exist in adults; researchers have found that they are still functional. This suggests that there are epigenetic changes that occur as a result of aging to make the adult cochlea less receptive to regeneration. Targeting epigenetic enzymes in addition to the Wnt and Notch signaling pathways may therefore prove more successful, but researchers still need to determine which part of the chromosome to target. This process would involve gene-editing techniques like CRISPR. This type of epigenome editing has slowed hearing loss in newborn mice, but it has yet to be tried in adult mice. If successful, this technique has the potential to treat hereditary and acquired forms of hearing loss.

HRP consortium member Alain Dabdoub, Ph.D., is a senior scientist, biological sciences at Sunnybrook Research Institute, University of Toronto. For more, see hhf.org/hrp.

Outsmarting the Most Common Military Injury: How One Veteran Is Helping Future Generations

By Imani Rodriguez

After 26 years of military service, Hearing Health Foundation (HHF) Board Chair Col. John Dillard (U.S. Army, Ret.) lives with tinnitus and noise-induced hearing loss. Tinnitus is one of the most prevalent war injuries among American veterans—and hearing loss is equally common—and Dillard is dedicated to improving the lives of millions through the advancement of tinnitus research that will lead to more reliable treatments and, eventually, permanent relief through cures. Tinnitus is the perception of ringing or buzzing in the ears without an external sound source.

In addition to supporting the advancement of more viable treatments and cures for tinnitus through HHF’s groundbreaking research, Dillard is a U.S. Department of Defense consumer reviewer for the Peer Review Medical Research Program (PRMRP), part of the U.S. government’s Congressionally Directed Medical Research Programs. 

Dillard is actively serving as a tinnitus consumer reviewer for the fourth consecutive year after again meeting qualifications through a rigorous application process. As a senior lecturer for systems acquisition management at the Naval Postgraduate School in Monterey, California, he is well connected with members of the military community, many who also live with tinnitus. He is a valuable contributor to discussions about tinnitus with scientists and the general public alike.

As a tinnitus consumer reviewer for the PRMRP, Dillard is responsible for evaluating and scoring tinnitus research proposals based on their potential for scientific and clinical impact. His academic experience as a military researcher has allowed him to assist with the critical thinking and reasoning aspects of each proposal. And from his own military experience, Dillard is keenly aware of how vital this research is for those returning from combat.

Tinnitus is a chronic condition without an existing reliable treatment, although certain products on the market claim otherwise. “There are no nutritional, pharmacological, surgical, deep brain or transdermal electrical stimulation, sound, transcranial magnetic, or other therapies proven efficacious for tinnitus,” Dillard says. “There are many treatments marketed to the naive consumer or patient/sufferer, but none of them are truly effective. Most folks who know me understand my extreme cautions against what I consider ‘snake oil’ treatments. People should spend no money on these products.”

Dillard says one exception using sound therapy is Tinnitus Retraining Therapy (TRT), currently considered the gold standard in coping with—but not eliminating or curing—disruptive levels of tinnitus. “I have personally benefited from TRT,” he says. TRT involves wearing ear-level devices that work to deliver masking noise to the brain, with or without hearing amplification; the therapy can typically be incorporated into hearing aids. 

Dillard is confident progress will continue to be made by both HHF and the Department of Defense. “We know now that tinnitus is more of a ‘brain problem’ that usually starts from damage to the ear in the form of noise-induced hearing loss,” he says. 

“We need to help the brain heal itself and correct what is actually an auditory ‘hallucination’ of hyperactive neuronal activity. It’s a very resilient, maladaptive feedback loop that works much like learned pain,” Dillard adds “We also hope for various pharmacological approaches being tried that can help tamp down this hyperactivity. I’m hopeful that we will see progress on treating tinnitus in our lifetimes.”

Col. John Dillard (U.S. Army, Ret.) was appointed Chair of Hearing Health Foundation’s Board of Directors July 1, 2019, after joining the Board in February 2018. He wrote about his experience in the military and how it affected his hearing as the Fall 2017 Hearing Health cover story. HHF marketing and communications intern Imani Rodriguez studied communications and public relations at Rutgers University. 

2019-2020 Emerging Research Grantees Announced

By Christopher Geissler, Ph.D.

Hearing Health Foundation (HHF) is proud to announce the recipients of Emerging Research Grants (ERG) for the upcoming year (July 1, 2019 — June 30, 2020). Following a rigorous review process, our Scientific Review Committee and Council of Scientific Trustees, comprised of senior expert scientists and physicians from across the US, have chosen fourteen especially meritorious projects to fund, covering a broad range of hearing and balance science. We are pleased to be able to support the work of these promising researchers and look forward to learning about the advances they will undoubtedly make in the coming year and beyond.

This year’s ERG recipients are:

Dunia Abdul-Aziz, M.D.
Massachusetts Eye and Ear
Project: Targeting epigenetics to restore hair cells

Pierre Apostolides, Ph.D.
Regents of the University of Michigan
Project: Novel mechanisms of cortical neuromodulation

Micheal Dent, Ph.D.
University at Buffalo
Project: Noise-induced tinnitus in mice
Generously funded by The Les Paul Foundation

Vijayalakshmi Easwar, Ph.D.
University of Wisconsin Madison
Project: Neural correlates of amplified speech in children with sensorineural hearing loss
Generously funded by The Children’s Hearing Institute

Kristi Hendrickson, Ph.D.
University of Iowa
Project: Neural correlates of semantic structure in children who are hard of hearing
Generously funded by General Grand Chapter Royal Arch Masons

Hao Luo, Ph.D.
Wayne State University
Cochlear electrical stimulation induced tinnitus suppression and related neural activity change in the rat's inferior colliculus
Generously funded by General Grand Chapter Royal Arch Masons

Kristy Lawton, Ph.D.
Washington State University Vancouver
Project: Characterizing noise-induced synaptic loss in the zebrafish lateral line

Anat Lubetzky, P.T., Ph.D.
New York University
Project: A balancing act in hearing and vestibular loss: assessing auditory contribution to multisensory integration for postural control in an immersive virtual environment

David Martinelli, Ph.D.
University of Connecticut Health Center
Project: Creation and validation of a novel genetically-induced animal model for hyperacusis
Generously funded by Hyperacusis Research

Jameson Mattingly, M.D.
The Ohio State University
Project: Differentiating Ménière's disease and vestibular migraine using audiometry and vestibular threshold measurements

Vijaya Prakash Krishnan Muthaiah, P.T., Ph.D.
University at Buffalo
Project: Potential of inhibition of Poly ADP Ribose Polymerase as a therapeutic approach in blast induced cochlear and brain injury.
Generously funded by General Grand Chapter Royal Arch Masons

William “Jason” Riggs, Au.D.
The Ohio State University
Project: electrophysiological characteristics in children with auditory neuropathy spectrum disorder
Generously funded by General Grand Chapter Royal Arch Masons

Gail Seigel, Ph.D.
The Research Foundation of SUNY on behalf of the University at Buffalo
Project: Targeting microglial activation in hyperacusis

Victor Wong, Ph.D.
Burke Medical Research Institute
Project: Targeting tubulin acetylation in spiral ganglion neurons for the treatment of hearing loss

Very High-Frequency Hearing Loss and Tinnitus: Is There a Link?

By Julia Campbell, Au.D., Ph.D.

Tinnitus is theorized to possibly arise from decreased central inhibition related to cochlear damage, or hearing loss. A reduction in inhibition function would allow signals that are normally suppressed to be perceived, resulting in tinnitus. However, many individuals with clinically typical hearing also present with tinnitus.

In our earlier study, results indicated that despite an apparently intact peripheral auditory system, inhibitory function was atypical and significantly related to tinnitus severity among a population reporting mild tinnitus. With central inhibition lowered, signals that are typically dampened are able to be perceived, potentially resulting in tinnitus. Our paper also showed the utility of measuring central inhibition through cortical auditory evoked potentials (CAEPs), which are electrical responses in the brain that reveal levels of central inhibition.

Given the prior study’s results, we thought it is possible that hearing loss within extended high-frequency thresholds (10, 12.5, and 16 kilohertz), which are not typically assessed in the clinic, may negatively impact inhibitory function and subsequent gating measures.

For our follow-up research, published in the American Journal of Audiology on April 22, 2019, we examined the role of both extended high-frequency thresholds and sensory gating dysfunction, a measure of central inhibition abnormality, in typical-hearing adults with and without tinnitus. Results suggest that extended high-frequency thresholds do not correlate with CAEP amplitude gating indices—in other words, high-frequency hearing loss was not associated with decreased central inhibition.

CAEP gating waveforms in A) a typical-hearing subject without tinnitus and B) a typical-hearing subject with tinnitus. The solid line represents the CAEP response to the first stimulus (S1) in a tonal pair, and the dashed the CAEP response to the second stimulus (S2) in a tonal pair. Typical gating is observed when CAEP S2 amplitude is lower compared with CAEP S1 amplitude (A). Atypical gating occurs when CAEP S2 amplitude is equal to or larger than CAEP S1 amplitude (B).

However, we found an unexpected relationship in the tinnitus group: Those with better (lower) thresholds also presented with worse tinnitus. We believe this finding may be due to typical-hearing adults with better high-frequency hearing to be more aware of internal auditory signals, and thus perceive tinnitus. However, further research is needed to investigate this hypothesis.

In addition, atypical gating performance was observed in adults with a Tinnitus Handicap Inventory score over 6, which may demonstrate that tinnitus severity must reach a certain point in order for central gating deficits to be observed, or vice versa. A hierarchical multiple regression showed both extended high-frequency thresholds and atypical gating function to account for a significant 49 percent of tinnitus severity.

Therefore, auditory gating appears to be a useful objective measure for tinnitus severity, at least in adults with clinically typical hearing. It also appears that the testing of extended high-frequency thresholds is warranted in this population, to be used in combination with CAEP amplitude gating indices. Our laboratory is now conducting studies investigating the utility of auditory gating as a clinical tool for the objective assessment of tinnitus severity in adults with hearing loss.

2016 Emerging Research Grants scientist Julia Campbell, Au.D., Ph.D., CCC-A, FAAA, received the Les Paul Foundation Award for Tinnitus Research. She is an assistant professor in communication sciences and disorders in the Central Sensory Processes Laboratory at the University of Texas at Austin. If you are interested in participating in this research, email julia.campbell@austin.utexas.edu.

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

Stability in an Unstable World

By Timothy S. Balmer, Ph.D., and Laurence O Trussell, Ph.D.

Balmer & Trussell traced the direct and indirect pathways that carry vestibular information to the cerebellum for controlling balance and posture. Shown here is a primary afferent axon (green) expressing the light-gated ion channel, Channelrhodopsin. Postsynaptic cells, in this case a unipolar brush cell (magenta), were recorded from during stimulation of the input axons by light flashes. This technique was used to discover how direct and indirect vestibular pathways are processed in the cerebellum.

Mice are helping scientists to understand how the world around us remains looking stable even as we move.

While out jogging, you have no trouble keeping your eyes fixed on objects in the distance even though your head and eyes are moving with every step. Humans owe this stability of the visual world partly to a region of the brain called the vestibular cerebellum. From its position underneath the rest of the brain, the vestibular cerebellum detects head motion and then triggers compensatory movements to stabilize the head, body and eyes.

The vestibular cerebellum receives sensory input from the body via direct and indirect routes. The direct input comes from five structures within the inner ear, each of which detects movement of the head in one particular direction. The indirect input travels to the cerebellum via the brainstem, which connects the brain with the spinal cord. The indirect input contains information on head movements in multiple directions combined with input from other senses such as vision.

Balmer & Trussell traced the direct and indirect pathways that carry vestibular information to the cerebellum for controlling balance and posture. Direct projections from the vestibular inner ear (green) and indirect projections from the brainstem (magenta) were shown to target different populations of neurons in the cerebellum.

By studying the mouse brain, Balmer and Trussell have now mapped the direct and indirect circuits that carry sensory information to the vestibular cerebellum. Both types of input activate cells within the vestibular cerebellum called unipolar brush cells (UBCs). There are two types of UBCs: ON and OFF. Direct sensory input from the inner ear activates only ON UBCs. These cells respond to the arrival of sensory input by increasing their activity. Indirect input from the brainstem activates both ON UBCs and OFF UBCs. The latter respond to the input by decreasing their activity.

The vestibular cerebellum thus processes direct and indirect inputs via segregated pathways containing different types of UBCs. The next step in understanding how the cerebellum maintains a stable visual world is to identify the circuitry beyond the UBCs. Understanding these circuits will ultimately provide insights into balance disorders, such as vertigo.

A 2017 Emerging Research Grants (ERG) scientist who received the Les Paul Foundation Award for Tinnitus Research, Timothy Balmer, Ph.D., is a postdoctoral fellow at the Oregon Hearing Research Center at Oregon Health & Science University (OHSU). Laurence Trussell, Ph.D., a 1991 ERG recipient, is a professor of otolaryngology–head and neck surgery at OHSU.

This research summary was repurposed with permission from eLife with permission.