Noise-Induced Brain Inflammation May Result in Painful Hearing
By Drs. Senthilvelan Manohar, Kelly Radziwon, and Richard Salvi
What do jet engines, sirens, and rock bands have in common? The sounds they emit are so intense that they are not only loud, but also painful, sometimes evoking a painful sensation around the external ear. The acoustic threshold for pain, 130-140 dB SPL, is intense enough to destroy or damage the delicate sensory hair cells, supporting cells and auditory nerve fibers in the inner ear. The axons from the auditory nerve deliver their messages to neurons located in the cochlear nuclei in the brainstem.
In a recent paper published in Molecular and Cellular Neuroscience, Drs. Baizer and Manohar at the University at Buffalo were surprised to find that intense noise exposures that destroyed the sensory hair cells in the rat inner ear led to a prolonged period of auditory nerve fiber degeneration in the cochlear nucleus in the brainstem (Bazier et al., Neuroscience 303 (2015) 299–311). Nerve fiber degeneration was still occurring 6-9 months post-exposure, nearly a third of the rat’s lifespan. In brain regions where the fibers were degenerating, there was robust upregulation of brain immune cells (microglia), indicative of long-term neuro-inflammation triggered by the release of inflammatory molecules in the brain. Since sensory nerve fibers (e.g., pain, touch) from the face, head, neck and shoulders (facial, trigeminal and spinal nerves) enter the cochlear nucleus, the long-term neuro-inflammation occurring in this region could lower pain thresholds (hyperalgesia). If this were to occur, much lower, moderate-intensity sounds (60-80 dB) might be sufficient to cause hyperacusis (loudness intolerance) with ear pain.
With funding from the Hearing Health Foundation obtained by Drs. Radziwon* and Manohar to identify pain-related molecules in the auditory pathway as a result of noise exposure, Drs. Manohar, Adler, and Salvi carried out a second study in which they measured noise-induced changes in the expression (amount) of genes involved in the synthesis of proteins known to be involved in neuropathic pain and neuro- inflammation. Interestingly, the researchers found that intense noise exposure significantly altered the expression of six genes (Ccl12, Tlr2, Oprd1, II1b, Ntrk1 & Kcnq3) in the cochlear nucleus (Manohar et al., Molecular and Cellular Neuroscience 75 (2016) 101–112). These results suggest that noise-induced inflammation in the parts of the central auditory pathway that also processes sensory information related to pain might, in turn, activate the central pain pathway thus producing ear pain. Determining whether neuro-inflammation is directly responsible for ear pain will open the door for novel interventions to treat hearing loss and hyperacusis.
*Kelly Radziwon, Ph.D., is a 2015 Emerging Research Grants recipient. Her grant was generously funded by Hyperacusis Research Ltd. Learn more about Radziwon and her work in “Meet the Researcher.”
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.
The Les Paul Foundation Funds Music Camps, Classroom Projects, Museums, Hearing Health Programs and Veterans' Recovery
New York, New York – July 11, 2016 - The Les Paul Foundation, whose mission is to honor the legacy of Les Paul, has continued its commitment to provide funding to projects that share Les Paul’s spirit. In 2016, the recipient organizations represent issues that were important to Les Paul and share Les Paul’s vision and innovation with their programs.
“Les Paul encouraged all of us to be innovative and create opportunities so the world would become a better place,” said Michael Braunstein, Executive Director of the Les Paul Foundation. “The organizations that have received grants perpetuate many of his philosophies and ideas. This allows us at the foundation to continue his legacy and show support for his values.”
Organizations that have benefitted from recent Les Paul Foundation grants include:
Birch Creek Music Performance Center of Egg Harbor, WI offers a summer guitar master class that includes Les Paul’s inventions, experiments and recording technique.
The Bonaroo Works Fund of Nashville, TN coordinated with the Les Paul Foundation to present the first ever Les Paul Spirit Award. The Bonaroo Works Fund supports education, music and arts programs for children or communities, protection of the environment and environment sustainability, and the arts/humanities in middle Tennessee.
The Boys & Girls Clubs of Martin County of Hobe Sound, FL weaves Les Paul’s contribution to rock and roll into their Les Rock program. Youth, ages 8 – 18, learn about Les’ contribution to music production including multi-tracking.
Camp Spin Off Foundation of Las Vegas, NV, provides 13-17 year olds an opportunity to learn about music production, remixing, music business and how to DJ. Campers learn how crucial Les Paul’s recording innovations were to how music is produced today.
Discovery World in Milwaukee, WI is reinforcing its Les Paul House of Sound exhibit with two new Les Paul-based school programs.
First Stage Milwaukee in Milwaukee, WI is sharing Les Paul’s stories of perseverance and innovation with elementary students. Through the dramatic process, students explore Les Paul’s inventions, his influence on the music industry, his creativity and his ability to overcome life’s challenges.
Hearing Education and Awareness for Rockers located in San Francisco, CA continues to include Les Paul in its presentations to music and sound arts schools and in its on-line presence. The organization focuses on encouraging youth to handle the power of sound in a safe manner.
The Hearing Health Foundation, headquartered in New York, NY, is the largest nonprofit supporter of hearing research. The Les Paul Foundation Award for Tinnitus Research is awarded annually to the most promising researcher studying the cause of ringing in the ears. This year’s recipient is Julia Campbell, Ph.D, Au.D, CCC-A, F-AAA, Assistant Professor, Communication Sciences and Disorders at The University of Texas at Austin.
“I am deeply honored to have received a grant award from the Les Paul Foundation to study brain function in the perception of tinnitus. Tinnitus is a disorder that affects millions of people around the world, and yet we still have no way to measure this disorder or a cure for it. Les Paul was an innovator, a dreamer, and a doer who loved to bring new sound into people’s lives. I believe that his legacy is an inspiration to not only better understand tinnitus, but to use this knowledge to improve the quality of life in those it affects,” said Campbell.
Legacy Music Alliance in Salt Lake City, UT uses Les Paul’s story from the Les Paul Foundation website in guitar programs, which are taught in Utah’s schools. Musical instruments are purchased and provided to Utah schools for use by students.
Litchfield Music Alliance of Litchfield, CT hosts Nicki Parrott of the Les Paul Trio at its master classes. Nicki tells Les’ story and includes his music in her classes.
Mahwah Museum Society of Mahwah, NJ will be integrating digital technology into its permanent Les Paul exhibit to increase visitors’ access to documents, photos and videos of Les Paul.
Six String Heroes of Jefferson Barracks in O’Fallon, MO use music to help injured veterans heal physical and mental wounds. The group shares Les’ story of perseverance and how Les experienced the healing power of music.
VHI Save the Music of New York, NY receives funding for its program to reintroduce music into public schools across the United States through its supply of musical instruments to schools in need. Each school will receive copies of a student-friendly biography of Les Paul for use by students.
Waukesha Community Art Project of Waukesha, WI will relay Les Paul’s love of music and his unending curiosity and relentless search for answers to inspire students to ask their own questions and make their own discoveries.
Wisconsin School Music Association of Madison, WI will guide student musicians through the maze of music business so that they can succeed and protect their work. Les Paul’s story will illustrate for students how success comes from never giving up.
Women’s Audio Mission of San Francisco, CA focuses on advancing women in music production and technology. Les Paul’s story inspires students in their hands-on electronics projects. The organization aims to cultivate the female version of Les Paul.
For more information on the Les Paul Foundation go to www.lespaulfoundation.org. Join the conversation at www.facebook.com/lespaulfoundation or www.twitter.com/lespaulfoundation
Grant applications are accepted twice a year. http://www.lespaulfoundation.org/programs/.
PRESS CONTACT
Caroline Galloway
(440) 591-3807 caroline@m2mpr.com
Neural sensitivity to binaural cues with bilateral cochlear implants
By Massachusetts Eye and Ear/Harvard Medical School
Many profoundly deaf people wearing cochlear implants (CIs) still face challenges in everyday situations, such as understanding conversations in noise. Even with CIs in both ears, they have difficulty making full use of subtle differences in the sounds reaching the two ears (interaural time difference, [ITD]) to identify where the sound is coming from. This problem is especially acute at the high stimulation rates used in clinical CI processors.
A team of researchers from Massachusetts Eye and Ear/Harvard Medical School, including past funded Emerging Research Grantee, Yoojin Chung, Ph.D., studied how the neurons in the auditory midbrain encode binaural cues delivered by bilateral CIs in an animal model. They found that the majority of neurons in the auditory midbrain were sensitive to ITDs, however, their sensitivity degraded with increasing pulse rate. This degradation paralleled pulse-rate dependence of perceptual limits in human CI users.
This study provides a better understanding of neural mechanisms underlying the limitation of current clinical bilateral CIs and suggests directions for improvement such as delivering ITD information in low-rate pulse trains.
The full paper was published in The Journal of Neuroscience and is available here. This article was republished with permission of the Massachusetts Eye and Ear/Harvard Medical School.
Dr. Yoojin Chung, Ph.D. was a 2012 and 2013 General Grand Chapter Royal Arch Masons International award recipient through our Emerging Research Grants program. Hearing Health Foundation would like to thank the Royal Arch Masons for their generous contributions to Emerging Research Grantees working in the area of central auditory processing disorders (CAPD). We appreciate their ongoing commitment to funding CAPD research.
We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.
Brain and Alzheimer's Disease Awareness Month
By Morgan Leppla
Bodies are complex systems, composed of many minute details. The human anatomy serves to remind us of the intricacies of our world. This June for Brain and Alzheimer’s Awareness Month, Hearing Health Foundation (HHF) invites you to join us in celebrating one of the most mysterious and fascinating part of the body: the brain.
For one to grasp the physiological complexity of being human, one ought to understand how their body’s many systems work in tandem. For example, each person’s brain depends on stimulation to keep it in tip-top shape and and their bodies depend on their brains to function as they are intended to.
This is clearly a stripped down explanation of the role brains play. Of course an organism’s structure can be broken down into smaller and smaller parts, so let’s focus on one of special importance to us here at HHF, hearing.
Frank Lin, M.D., Ph.D., from Johns Hopkins University reports in 2014 that hearing loss affects brain structure, and specifically accelerates brain tissue loss. The study was conducted over a 10-year period with a sampling of people which included those with substantial hearing loss and those with normal hearing. After analyzing years of magnetic resonance imaging scans, his conclusions suggest people with substantial hearing loss show higher rates of brain atrophy. Lin explains brain shrinkage could be the result of an “‘impoverished’ auditory cortex” since there is reduced brain stimulation in that area.
"If you want to address hearing loss well," Lin says, "you want to do it sooner rather than later. If hearing loss is potentially contributing to these differences we're seeing on an MRI, you want to treat it before these brain structural changes take place."
The human brain contains some of the most challenging biological mysteries in science (and always has). Unlocking those takes perseverance, so HHF thanks brain and hearing researchers for the time and energy devoted to rigorous research and ultimately revealing information critical to improving brain health.
Parts really do affect the health of the whole. So for the brain and beyond, please make an appointment with your hearing healthcare professional for your annual checkup and, if you are diagnosed with a hearing loss, managing it. More than just your hearing will benefit! Untreated hearing loss has been linked to dementia, depression, diabetes, falls, and heart disease.
Want to learn more about brain health? Check out last year’s blog here: Your Brain Is a Muscle: Use It or Lose It
NEWS UPDATE: Report on Hearing Health Care Released
By Morgan Leppla
Did you know it is estimated that 67 to 86 percent of people who might benefit from hearing aids do not have them? In a much-anticipated National Academies of Sciences, Engineering, and Medicine (NAS) report, published on June 2, 2016, NAS addresses the areas of hearing healthcare that currently prevent many of the 48 million Americans with hearing loss from seeking treatment, and provide 12 recommendations for improvement.
The NAS report recognizes that hearing loss detracts from individuals’ participation in family life, school, and work, and can affect anyone, young or old. People deserve the ability to communicate effectively, live healthily, and enjoy a high quality of life.
Specifically, the report recommends “key institutional, technological, and regulatory changes that would enable consumers to find and fully use the appropriate, affordable, high-quality services, technologies, and support they need.”
Currently, hearing healthcare is not focused on the consumer. However, through implementing the report’s recommendations, it would improve:
The quality and affordability of hearing healthcare
Access to accurate information that should be readily available to the public
Increasing the number of options for consumers to choose from, in order to best fit individual needs
Reducing stigma and bettering education
Ending governmental measures that create obstacles to easy access
The NAS report further explains that this is everyone’s responsibility to manage their hearing health: Cross-sector, sustained collaboration is crucial to successful implementation of the report’s blueprint.
"Hearing Health Foundation (HHF) recommends everyone talk to their doctors to identify any hearing loss as well as to find the best hearing loss treatment for them. HHF is dedicated to funding research to cure and treat hearing loss and tinnitus and is proud to play a role in pushing hearing and balance research forward,” says Nadine Dehgan, HHF CEO.
HHF would like to thank the NAS and its expert committee for their hard work in preparing this report, including the committee’s Judy R. Dubno, Ph.D., a member of HHF’s Board of Directors, and Debara L. Tucci, M.D., a member of HHF’s Council of Scientific Trustees.
Hearing Aid Use Is Associated with Improved Cognitive Function in Hearing-Impaired Elderly
By Columbia University Medical Center
A study conducted by researchers at Columbia University Medical Center (CUMC) found that older adults who used a hearing aid performed significantly better on cognitive tests than those who did not use a hearing aid, despite having poorer hearing.
The study was published online in the American Journal of Geriatric Psychiatry.
The researchers also found that cognitive function was directly related to hearing ability in participants who did not use a hearing aid.
More than half of adults over age 75 have hearing loss, yet less than 15 percent of the hearing impaired use a hearing aid device. Previous studies have shown that the hearing-impaired elderly have a higher incidence of fall- and accident-related death, social isolation, and dementia than those without hearing loss. Studies have also demonstrated that hearing aid use can improve the social, functional, and emotional consequences of hearing loss.
“We know that hearing aids can keep older adults with hearing loss more socially engaged by providing an important bridge to the outside world,” said Anil K. Lalwani, MD, professor of otolaryngology/head and neck surgery at Columbia and otolaryngologist at NewYork-Presbyterian/CUMC and NewYork-Presbyterian/Morgan Stanley Children’s Hospital. “In this study, we wanted to determine if they could also slow the effects of aging on cognitive function.”
The study included 100 adults with hearing loss between the ages of 80 and 99. Of the participants, 34 regularly used a hearing aid. Audiometry tests were performed to measure the degree of hearing loss. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE), in which participants give vocal responses to verbal commands. Executive function was also assessed with the Trail Making Test, Part B (TMT-B), which does not have a verbal or auditory component.
Hearing aid users, who had worse hearing than non-users, performed significantly (1.9 points) better on the MMSE. Among non-users, participants with more hearing loss also had lower MMSE scores than those with better hearing. Although hearing aid users performed better than non-users on the TMT-B, the difference was not statistically significant. In addition, TMT-B scores were not correlated with hearing level.
“Our study suggests that using a hearing aid may offer a simple, yet important, way to prevent or slow the development of dementia by keeping adults with hearing loss engaged in conversation and communication,” said Dr. Lalwani.
This blog was reposted with the permission of Columbia University Medical Center.
Anil K. Lalwani, M.D. is the Head of Hearing Health Foundation's Council of Scientific Trustees and sits on our Board of Directors.
We need your help in funding the exciting work of hearing and balance scientists.
To donate today to support HHF's groundbreaking research,
please visit hhf.org/donate.
Unraveling Genes Critical for Inner Ear Development
By Albert Edge, Ph.D., and Alain Dabdoub, Ph.D
The goal of the Hearing Restoration Project (HRP) is to determine how to regenerate inner ear sensory cells in humans to eventually restore hearing for millions of people worldwide. These sensory cells, called hair cells, in the cochlea detect and turn sound waves into electrical impulses that are sent to the brain. Once hair cells are damaged or die, hearing is impaired, but in most species, hair cells spontaneously regrow and hearing is restored. The HRP is aiming to enable this ability in humans.
All cells develop through a chain of events triggered by chemical signals (proteins) from outside the cell. The signals kick off responses inside the cell that can change the cell’s ability to proliferate (grow and divide) and differentiate (take on specialized functions).
The Wnt signaling pathway, a sequence of events triggered by the Wnt protein, helps guide inner ear cell development, including the proliferation of cells that differentiate into the hair cells and supporting cells necessary for hearing and balance. But in mice and other mammals, inner ear cell proliferation does not continue past newborn stages.
Underscoring their importance in evolutionary terms, Wnt signals occur across species, from fruit flies to humans—the “W” in Wnt refers to “wingless”—and Wnt signaling is guided by dozens of genes. Albert Edge, Ph.D., Alain Dabdoub, Ph.D., and colleagues performed a comprehensive screen of 84 Wnt signaling-related genes and identified 72 that are expressed (turned on) during mouse inner ear development and maturation. Their results appeared in the journal PLoS One this February.
The Wnt signaling network has three primary pathways. Two are known to be integral to the formation of the mammalian inner ear, including the determination of a cell’s “fate,” or what type of cell it ultimately turns into. This is particularly significant because the inner ear’s sensory epithelium tissue is a highly organized structure with specific numbers and types of cells in an exact order. The precise arrangement and number of hair cells and supporting cells is essential for optimal hearing.
The relationship between the Wnt-related genes, the timing of their expression, and the various signaling pathways that act on inner ear cells is extremely complex. For instance, the composition of components inside a cell in addition to the cell’s context (which tissue the cell is in, and the tissue’s stage of development) will influence which pathway Wnt signaling will take. It is known that inhibiting the action of Wnt signaling causes hair cells to fail to differentiate.
The new research complements previous chicken inner ear studies of Wnt-related genes as well as a recent single-cell analysis of the newborn sensory epithelium in mice (conducted by HRP scientist Stefan Heller, Ph.D., and colleagues). Comprehensively detailing these 72 Wnt-related genes in the mouse cochlea across four developmental and postnatal time periods provides a deeper understanding of a critical component of hair cell development, bringing the HRP closer to identifying genes for their potential in hair cell regeneration.
Your Support Is Needed!
Hair cell regeneration is a plausible goal for eventual treatment of hearing and balance disorders.
The question is not if we will regenerate hair cells in humans, but when.
However, we need your support to continue this vital research and find a cure!
Please make your gift today.
Are Hair Cell Regeneration Genes Blocked?
By Yishane Lee
On March 8, 2016, Hearing Health Foundation hosted a live-video research briefing, as part of an ongoing effort to provide regular updates on our research programs and progress. Through these briefings, our goal is for our attendees to learn new information and achieve a greater understanding of hearing loss, prevention, and to o develop effective therapies for hearing loss and tinnitus.
Peter Barr-Gillespie, Ph.D., the scientific director of the Hearing Restoration Project (HRP), began the webinar with announcing the newest HRP consortium member, Ronna Hertzano, M.D., Ph.D., from the University of Maryland. Ronna is a clinician as well as a research scientist, a rare combination and an asset for the HRP. She also developed a bioinformatics platform, gEAR, that the HRP is using to efficiently compare large, complex genetic datasets between species.
Dr. Barr-Gillespie went on to outline a year in the life of the HRP—how the investigators collaborate, discuss, and develop research projects. He then provided an overview of a currently funded project focused on examining whether genes can be manipulated to overcome a block to hair cell regeneration in mammals, including humans. The advancements in technologies, such as CRISPR gene modification, provides the HRP with the ability to study hair cell regeneration in different species and at a level of detail and manipulation unheard of before.
We invite you to watch the video with captioning, or read the presentation with summary notes. We are excited to share this discussion of the HRP’s progress to date and our plans for 2016 and beyond.
Your Support Is Needed!
Hair cell regeneration is a plausible goal for eventual treatment of hearing and balance disorders.
The question is not if we will regenerate hair cells in humans, but when.
However, we need your support to continue this vital research and find a cure!
Please make your gift today.
Defining Auditory-Visual Objects
By Molly McElroy, PhD
If you've ever been to a crowded bar, you may notice that it's easier to hear your friend if you watch his face and mouth movements. And if you want to pick out the melody of the first violin in a string quartet, it helps to watch the strokes of the players' bow.
I-LABS faculty member Adrian KC Lee and co-authors use these examples to illustrate auditory-visual objects, the topic of the researchers' recently published opinion paper in the prestigious journal Trends in Neurosciences.
Lee, who is an associate professor in the UW Department of Speech & Hearing Sciences, studies brain mechanisms that underlie hearing. With an engineering background, Lee is particularly interested in understanding how to improve hearing prosthetics.
Previous I-LABS research has shown that audio-visual processing is evident as early as 18 weeks of age, suggesting it is a fundamental part of how the human brain processes speech. Those findings, published in 1982 by the journal Science, showed that infants understand the correspondence between sight and the sound of language movements.
In the new paper, Lee and co-authors Jennifer Bizley, of University College London, and Ross Maddox, of I-LABS, discuss how the brain integrates auditory and visual information—a type of multisensory processing that has been referred to by various terms but with no clear delineation.
The researchers wrote the paper to provide their field with a more standard nomenclature for what an audio-visual object is and give experimental paradigms for testing it.
“That we combine sounds and visual stimuli in our brains is typically taken for granted, but the specifics of how we do that aren’t really known," said Maddox, a postdoctoral researcher working with Lee. “Before we can figure that out we need a common framework for talking about these issues. That’s what we hoped to provide in this piece.”
Trends in Neurosciences is a leading peer-reviewed journal that publishes articles it invites from leading experts in the field and focuses on topics that are of current interest or under debate in the neuroscience field.
Multisensory, especially audio-visual, work is of importance for several reasons, Maddox said. Being able to see someone talking offers huge performance improvements, which is relevant to making hearing aids that take visual information into account and in studying how people with developmental disorders like autism spectrum disorders or central auditory processing disorders (CAPD) may combine audio-visual information differently.
"The issues are debated because we think studying audio-visual phenomena would benefit from new paradigms, and here we hoped to lay out a framework for those paradigms based on hypotheses of how the brain functions," Maddox said.
Read the full paper online. This article was republished with permission of the Institute for Learning & Brain Sciences at the University of Washington.
Ross Maddox, Ph.D. was a 2013 General Grand Chapter Royal Arch Masons International award recipient. Hearing Health Foundation would like to thank the Royal Arch Masons for their generous contributions to Emerging Research Grantees working in the area of central auditory processing disorders (CAPD). We appreciate their ongoing commitment to funding CAPD research.
We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.
