Tag Archives: hearing loss

Permanent hearing loss may not be so permanent after all — in mice, for now

Credit: Pixabay.

Once we damage sensory cells in the inner ear, either due to some accident or simply growing old, this damage is irreversible, leading to hearing loss. However, there may be a way to regenerate some of these cells. In a remarkable new study, researchers at the University of Southern California have identified a molecular pathway that, when activated, may trigger the regeneration of lost sensory cells, thereby restoring hearing. Although the findings apply to mice, targeted therapy may also work on other mammals, including humans.

Approximately one in three people between the ages of 65 and 74 has hearing loss, and nearly half of those older than 75 have difficulty hearing.  The most common type is sensorineural hearing loss caused by the degradation and loss of sensory hair cells in the cochlea (the auditory part of the inner ear).

Hair cells are the sensory receptors for both the auditory system and the vestibular system in our ears — and the ears of all vertebrates. These hair-like projections play a big part in both our hearing and our balance, transforming the sound vibrations in the cochlea into electrical signals which are fed to auditory nerves and sent up to the brain.

But there’s a second type of sensory cell in the cochlea called “supporting cells”. As the name suggests, these cells play a secondary role in hearing by supporting important structural and functional processes.

Previously, scientists were stunned to find that lab mice who had suffered damage to their cochlea transformed supporting cells into hair cells through a process known as “transdifferentiation”, recovering some of their hearing. However, this only happened in mice who were only a few days old. Once they grew older, they lost this ability.

Credit: Developmental Cell.

Scientists think that humans may also possess this regenerative capacity but likely only while still developing as an embryo. By the time humans are born, this ability is probably long gone.

Starting from these observations, lead authors Litao Tao and Haoze “Vincent” Yu zoomed in on the molecular mechanisms that support transdifferentiation in mouse pups and the neonatal changes that block this process.

According to the investigation, the transdifferentiation of supporting cells is mediated by hundreds of genes that are normally turned off but which get switched on in the presence of activating molecules. Conversely, these genes can be turned off by the presence of repressive molecules. These alterations are known as “epigenetic modifications” and play a huge role in regulating gene activity and controlling the properties of the genome.

In experiments with supporting cells from newborn mouse cochleas, the scientists found that hair cell genes were suppressed by both the lack of an activating molecule, H3K27ac, and the presence of the repressive molecule, H3K27me3. However, juggling these molecules alone is not enough to convert supportive cells into hair cells. An additional molecule H3K4me1 primes these genes for activation and hair cell development.

Due to the aging process, the H3K4me1 priming molecule is lost. But when the scientists introduced a drug that prevents the loss of H3K4me1, the supporting cells stayed primed for transdifferentiation despite the advanced age of the cells, as reported in the journal Developmental Cell.

“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing,” said Segil in a statement. “Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart.”

Elsewhere, researchers at the University of Rochester tweaked a group of epidermal growth factor (EGF) receptors that are known to be responsible for activating support cells in the auditory organs of birds. Through a combination of drugs originally developed to stimulate stem cell activity and genetic modification, they were able to activate the same molecular pathway in mice. This led to the proliferation of cochlear support cells, triggering neighboring stem cells to develop into new sensory hair cells.

Repairing hearing is a complex problem. Not only do hair cells require regeneration, but they also have to connect properly to the necessary network of neurons. But these promising studies show that at some time in the future, growing old may not necessarily mean bad hearing anymore. 

Difficulties hearing speech over noise? That may be an early sign of dementia, new study says

Researchers at the University of Oxford found evidence that elderly people showing difficulty hearing spoken conversations in relatively noisy environments, such as a bustling street or pub, may face an up to 91% increased risk of dementia later in life.

Credit: Pixabay.

According to the World Health Organization (WHO), up to 1.5 billion individuals suffer from some form of hearing impairment. Approximately 30 percent of adults aged 65 and older, and 55 percent older than 80 years show some degree of hearing loss. Besides affecting their quality of life, this disability may also contribute to the risk of dementia.

In a 2015 study, researchers at Johns Hopkins found that mild hearing loss doubled dementia risk and moderate loss tripled the risk. People with a severe hearing impairment were five times more likely to develop dementia.

“Brain scans show us that hearing loss may contribute to a faster rate of atrophy in the brain,” said Frank Lin, the director of the Cochlear Center for Hearing and Public Health at Johns Hopkins . “Hearing loss also contributes to social isolation. You may not want to be with people as much, and when you are you may not engage in conversation as much. These factors may contribute to dementia.”

Although the exact association between hearing loss and dementia is unclear, emerging research suggests that poor hearing may impact memory care drastically in the coming years.

A hallmark of hearing impairment is difficulty understanding speech in noisy environments, which scientists refer to as speech-in-noise hearing impairment. However, up until very recently, it was unclear if this particular facet of hearing impairment was associated with developing dementia. Turns out it is, according to researchers at the University of Oxford’s Nuffield Department of Population Health.

“Difficulty hearing speech in background noise is one of the most common problems for people with age-related hearing impairment. This is the first study to investigate its association with dementia in a large population,” said Dr. Jonathan Stevenson, lead author of the new study.

Stevenson and colleagues surveyed 82,000 men and women aged 60 years or older who enrolled in the UK Biobank program. The participants had to identify certain spoken words against a background of white noise. Based on their scores, they were divided into three distinct groups: normal, insufficient, and poor speech-in-noise hearing.

Over 11 years of follow-up, 1,285 participants developed or were in the course of developing dementia. When the researchers modeled their hearing loss scores and adjusted for other factors, they were stunned to find insufficient and poor speech-in-noise hearing were associated with a 61% and 91% increased risk of developing dementia, compared to normal speech-in-noise hearing, respectively.

In order to explain how hearing impairment may lead to dementia, some have suggested that hearing impairment could lead to social isolation and depression, and it is these factors that actually later contribute to dementia. However, this new research found no such evidence.

“While most people think of memory problems when we hear the word dementia, this is far from the whole story. Many people with dementia will experience difficultly following speech in a noisy environment – a symptom sometimes called the ‘cocktail party problem’. This study suggests that these hearing changes may not just be a symptom of dementia, but a risk factor that could potentially be treated,” Dr. Katy Stubbs from Alzheimer’s Research UK said in a statement.

The good news is that speech-in-noise hearing impairment is very easy to diagnose, so it could provide people with an early warning sign that dementia may be looming. Although there is no cure for dementia, it can be postponed and managed as long as precautions are taken years in advance.

“Dementia affects millions of individuals worldwide, with the number of cases projected to treble in the next few decades. However, there is growing evidence that developing dementia is not inevitable and that the risk could be reduced by treating pre-existing conditions. Whilst preliminary, these results suggest speech-in-noise hearing impairment could represent a promising target for dementia prevention,” said Dr. Thomas Littlejohns, senior epidemiologist in the Nuffield Department of Population Health(NDPH), and senior author of the study.

The findings appeared in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association..

How a deaf Beethoven discovered bone conduction by attaching a rod to his piano and clenching it in his teeth

On May 7, 1824, the legendary 9th Symphony premiered in the Theater am Kärntnertor in Vienna. When the masterful performance ended, 54-year-old Beethoven, who was stone deaf at this time, was still conducting along with the “official conductor” from the front row when he had to be turned around to face the thunder of an applauding audience.

Whilst Beethoven’s career was the stuff of genius, his personal life was marked by a struggle against deafness and constant suffering caused by an armada of afflictions. The German composer first noticed that his hearing was fading around the age of 28. By this time he was already an established figure in the Vienna musical scene and regarded as a rising star rivaling Wolfgang Amadeus Mozart, which only made everything worse.

One can only imagine how cruel a fate that must have felt like to such a musical mind. He, the great Beethoven, of all people, was going deaf! It’s as if Picasso lost his eyesight or Rodin had his arms cut off.

But Beethoven was a strong-willed spirit who didn’t give up easily. One of his celebrated phrases is: “I will choke on the throat of fate, it will never make me succumb.”

He was true to his word. Despite his rapidly deteriorating hearing, from 1803 to 1812, Beethoven composed an opera, six symphonies, four solo concerti, five string quartets, six-string sonatas, seven piano sonatas, five sets of piano variations, four overtures, four trios, two sextets, and 72 songs.

Beethoven… the inventor?

Despite living in pain, Beethoven did not give up. However, he had a helping hand. In order to continue composing and playing music, Beethoven stumbled across a physical phenomenon that is central to hearing: bone conduction.

At the time, scientists understood very little about how human hearing works. But despite the fact that his ears left him, he could still hear himself playing music by placing one end of a wooden stick onto his piano and clenching on the other end with his teeth. When notes were struck, the vibrations from the piano were transferred to his jaw, and from there directly to his inner ear. Miraculously, he could hear again! Bone conduction was born.

Sound is nothing more than acoustic vibration in the air. These juggling atoms vibrating at certain frequencies cause the eardrum to vibrate, which are transformed into a different kind of vibration that the cochlea, also known as the inner ear, can interpret. The cochlea then transmits the information about the sound to the brain via the auditory nerve where it is processed as hearing.

But there’s a second way that humans can hear besides air conduction. If the inner ear is directly exposed to acoustic vibration in the bones, then a person can still hear although the eardrum is bypassed. This is one of the reasons you can still hear your own voice if you plug your ears. It’s also how whales hear while diving deep in the ocean or how male elephants can listen for mating calls by stomping females several kilometers away.

Beethoven’s clever bone-conducting solution is used in some hearing devices today. A bone conducting hearing device, or BAHA, converts the sound picked up by its microphone into vibrations that are transmitted through the bones of the skull to the cochlea of the inner ear. Essentially, the bone conducting device fills the role of a defective eardrum.

Bone conduction hearing devices are also used by people with perfect hearing in certain applications. For instance, military headsets allow soldiers to hear orders relayed through a bone conduction device, sometimes integrated into the helmet, despite the background noise of enemy gunfire. Special bone conduction hearing devices also allow divers to both hear and talk underwater.

Beethoven’s final struggles with deafness

The way Beethoven dealt with his deafness is one of the great stories of humanity. The cause of his deafness, though, remains something of a mystery.

His diagnosis is made all the more challenging since he suffered from a plethora of other illnesses. The list includes chronic abdominal pain and diarrhea that might have been due to an inflammatory bowel disorder, depression, alcohol abuse, respiratory problems, joint pain, eye inflammation, and cirrhosis of the liver. 

This last item, a consequence of his prodigious drinking, may have ultimately killed Beethoven, who died in 1827. An autopsy showed signs of severe cirrhosis, but also dilatation of the auditory and other related nerves in the ear.

As a common custom of the time, a young musician by the name of Ferdinand Hiller snipped off a lock of hair from Beethoven’s head as a keepsake. The lock stayed in the Hiller family for nearly a century until it somehow made its way into the hands of a Danish physician called Kay Fremming. The physician is famous for saving thousands of Jews during the occupation of Denmark by Nazi forces by helping them escape to Sweden, whose border was closeby to a tiny fishing village Fremming called home. Some speculate that one of the Jewish refugees gave Dr. Freeming the lock of Beethoven’s hair in gratitude for saving their lives.

What we know for sure is that the lock of hair, consisting of 582 strands, was passed down to Fremming’s daughter, who put it up for auction in 1994. It was purchased by Alfredo Guevara, an Arizona urologist, for a modest $7,000. Guevara kept a few strands and donated the rest to the Ira F. Brilliant Center for Beethoven Studies at San Jose State University in California.

At this point, scientists at the university thought of examining DNA from the great composer’s hair in order to look for clues as to how Beethoven became deaf.

The hair was put through a barrage of DNA, chemical, forensic, and toxicology tests. What immediately stood out was an abnormally high level of lead. During Beethoven’s time, people weren’t aware of lead poisoning and it was quite common to use plates for food and goblets for drinking made out of the toxic metal. Even the wine of that era, Beethoven’s favorite drink, often contained lead as a sweetener. This severe lead poisoning may have contributed to the composer’s lost hearing.

For a long time, Beethoven tried to conceal his deteriorating hearing, fearing that this may ruin his career if the word was out. But he couldn’t keep it up for too long. It was common for composers to also conduct and even perform their own music, and Beethoven’s condition eventually became noticeable. After watching one of Beethoven’s piano rehearsals in 1814, fellow composer Louis Spohr said “…the music was unintelligible unless one could look into the pianoforte part. I was deeply saddened at so hard a fate.”

At age 45, Beethoven’s hearing was completely gone, and so was his public life. In the final stretch of his life, the German composer became a reclusive, insular person who allowed only a select few friends to visit him. The music he composed during this time, which includes the famous Sixth Symphony, reflects Beethoven’s love for nature and his life in total silence in the countryside. Describing the Sixth Symphony, Beethoven said it is “more the expression of feeling than painting”, a point underlined by the title of the first movement. While completely deaf, Beethoven also composed Missa Solemnis, the solemn mass for orchestra and vocalists, and the opera Fidelio, among other major works.

It’s not clear if Beethoven’s inner ear was still functional in his later days so that he could continue using his bone-conducting stick to hear his compositions on the piano. Many experts believe he didn’t need to hear his pieces anyway since he was a master composer who knew all the rules of how music is made. Even in deafness, Beethoven was an unparalleled master of the language of music and an inspiration for resilience.

Credit: Pixabay.

Scientists regrow hair cells in mice, suggesting hearing loss is reversible after all

Credit: Pixabay.

Credit: Pixabay.

Hearing loss affects millions of people worldwide — a common health problem caused by noise, aging, disease, and heredity. Once a person loses part or all of their hearing, they cannot restore it. But is hearing loss really permanent? Not so fast, says a new study, which found that activating a certain signaling pathway caused mice to regrow hair cells.

Approximately one in three people between the ages of 65 and 74 has hearing loss, and nearly half of those older than 75 have difficulty hearing.  The most common type is sensorineural hearing loss caused by the degradation and loss of sensory hair cells in the cochlea (the auditory part of the inner ear).

Hair cells are the sensory receptors for both the auditory system and the vestibular system in our ears — and the ears of all vertebrates. They play a big part in both our hearing and our balance, transforming the sound vibrations in the cochlea into electrical signals which are fed up to auditory nerves and sent up to the brain.

If you’re a bird or frog, then you are able to regenerate hair cells. Unfortunately for humans, and all other mammals, we don’t have this ability.

“We’re the only vertebrates that can’t do it,” said Jingyuan Zhang, a researcher at the biology department at the University of Rochester, and co-author of the new study published in the European Journal of Neuroscience.

Zhang and colleagues wanted to find out whether they could treat the mammalian body into growing hearing cells, just like all other non-mammals can. They zoomed in on a group of epidermal growth factor (EGF) receptors that are known to be responsible for activating support cells in the auditory organs of birds. Once these cells are activated, they foster the generation of new sensory hair cells.

Mice, and likely all other mammals, express EGF receptors throughout their lives but are, nevertheless, unable to regenerate hair cells. The researchers at the University of Rochester have a hunch that during mammalian evolution, the expression of intracellular regulators of EGF receptors changed somehow, altering the signaling pathway. What if they could switch this pathway? That’s the million dollar question.

The team tested their theory by targeting a specific receptor called ERBB2 in cochlear support cells. In experiments, researchers used different methods to target the receptor, including a virus, drugs originally developed to stimulate stem cell activity but which are also known to activate ERBB2 signaling, and genetic modification of the mice themselves.

Activating the ERBB2 pathways unleashed a cascade of cellular events which eventually led to the proliferation of cochlear support cells, triggering neighboring stem cells to develop into new sensory hair cells.

“This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing,” said says lead author Patricia White, research associate professor in the University of Rochester Medical Center (URMC) Del Monte Institute for Neuroscience.

Repairing hearing is a complex problem. Not only do hair cells require regeneration, but they also have to connect properly to the necessary network of neurons. But the findings are definitely promising, suggesting that sometime in the future, growing old may not necessarily mean you’ll have bad hearing anymore.

 

Hearing loss and memory loss might go hand in hand

People suffering from a specific type of hearing loss might also be more prone to memory loss, a new study concludes.

Image credits: mike krzeszak / Flickr.

Hearing loss can have many causes. Instant or temporary loss can be caused by earwax, infections, injuries or other diseases, but the more common hearing loss is chronic. Gradual hearing degradation is usually caused by aging or repeated exposure to loud noises. Hearing loss is one of the most common disabilities for the elderly, with one in three people 65 and over suffering from it. Now, a new study raises even more concerns about this health issue, as researchers conclude that a certain type of hearing loss is associated with mild cognitive impairment.

Researchers recruited 1,604 participants from the Great Age Study, a population-based study conducted in the south of Italy, with an average age of 75, testing their hearing and cognitive skills. Out of the participants, 26 percent had some peripheral hearing loss and 12 percent had central hearing loss, while 33 percent were diagnosed with mild cognitive impairment. Peripheral hearing loss is typically associated with a degradation of the inner and hearing nerves, while central hearing loss is caused by problems in the brain’s ability to process sound.

[alert style=”alert-warning” close=”false”]People suffering from central hearing loss would say things like “I can hear you talking but I can’t understand.” For this reason, some classify it as a learning disability rather than a hearing loss. However, it is nevertheless a deficit located on the neural pattern of the auditory functions, and can therefore be regarded as a hearing disorder.

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Researchers found a significant correlation between central hearing loss and cognitive impairment. Out of the 192 people with central hearing loss, 144 of them — 75%, compared to 60% for people with no hearing loss — had mild cognitive impairment. However, the correlation didn’t carry over to people suffering from peripheral hearing impairment, who weren’t more likely to suffer from any cognitive degradation than people without any hearing loss.

“These preliminary results suggest that central hearing loss may share the same progressive loss of functioning in brain cells that occurs in cognitive decline, rather than the sensory deprivation that happens with peripheral hearing loss,” said study author Rodolfo Sardone AuD, EngD, MPh, at the National Institute of Health and University of Bari in Italy. “It’s a problem with perception. Tests of hearing perception should be given to people who are older than 65 and also to people with cognitive impairment.”

However, this study only established a correlation and didn’t seek to explain any causation. In other words, we don’t know if one is causing the other, or if they are unrelated. Still, Sardone has an idea about the mechanism behind this process. In an email to ZME Science, he wrote:

“Sensory deprivation leads to a weakening of the neural structures of the brainstem and the temporal cortex, very similar to the well-known neuroscientific concept of “use it or lose it.” A peripheral hearing loss increases the effort and therefore the cognitive load, specifically on the executive functions and working memory, precociously damaged in the degenerative processes like AD. This hypothesis does not explain why in about 9% subjects have speech abnormalities with a normal audiometric threshold.”

In the future, the team will try to find associations between central auditory processing disorder and mild memory impairment to back up their findings.

“The difference between our study and the others is that we’re trying to define the association in the very early stage of cognitive decline like mild memory impairment, and next step will be to explore with longitudinal observations the associations between CAPD and the subjective memory complaint,” Sardone told us.

The study hasn’t been yet peer-reviewed and will be presented at the American Academy of Neurology’s 70th Annual Meeting in Los Angeles.

Can Hearing Aids Also Save Your Memory?

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If you’ve ever lived with someone who’s hard of hearing, or have struggled with hearing difficulties yourself, you know it can be a hard condition to live with. Thankfully, modern technology has given us a wide variety of hearing implements that can let us salvage this precious physical sense.

But hearing loss can come with a number of related symptoms that are just as debilitating; those who live with moderate to severe hearing loss may also experience worsening memory and general mental confusion as their hearing slips away.

Scientists have believed for some time that these two conditions, while closely linked, would require different forms of treatment. But a recent study from Johns Hopkins has revealed that a familiar technology—hearing aids—may help to reverse the mental side-effects of hearing loss.

The impetus behind the study was the purported connection between hearing loss and an elevated risk of various cognitive problems. The study’s lead author, Jennifer Deal, has published previous work about this connection, but few studies have sought to study the connection in detail—until now. They’re hopeful that their findings will determine once and for all whether hearing aids are capable of staving off or even reversing a trend of worsening cognitive function.

The answer, so far, is yes they can.

Deal hailed the team’s findings, saying: “This study is important because it focuses on a risk factor that is amenable to intervention in later life and could potentially postpone cognitive decline.”

Deal and her team worked with a total of 253 people for the study, with an average age of 77 years. The patients all exhibited hearing loss described as “mild” to “moderate.” Each one was given a series of memory, learning, and reasoning tests way back in the early 1990’s. To truly test the long-term effects, the team waited until 2013 for a battery of follow-up tests.

And what did they find? It turns out that those participants who did not wear hearing aids in the intervening years posted the greatest drop in test scores. The ones who did wear hearing aids showed a slowing of their mental deterioration—a triumph both for this team of researchers and for modern hearing aid technology.

Most human beings know only too well that the gift of hearing is too easily squandered or damaged. Experiencing head trauma, listening to music too loud, getting clumsy on the Fourth of July, genetics, or merely growing older can all contribute to hearing loss later in life. But, while a person’s history and habits might give them some advanced warning that their hearing might one day be in danger, it can be tempting to ignore the problem—as well as the potential side-effects that come with it.

According to Dr. Alice Holmes, the study is important because it proves in a new way that hearing loss should not be ignored: “This shows we really should be treating hearing loss. I think treating the hearing loss can really improve someone’s overall quality of life and not only does it improve that quality of life but also others’ around him.”

So if you’re experiencing hearing loss, or know someone who is, now is the time to seek treatment. In addition to losing a part of your connection to the world around you, your mental health may suffer in some unexpected ways if you let your problem go untreated.

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Songbirds inspire next generation hearing aid, faithful to the human ear

Hearing loss can be devastating: you lose friends, become ever trapped inside your head and alienated from society. Yet, only one in five Americans choose to use a hearing aid. Some ignore their problem, others can’t afford treatment or installing a hearing aid, but really a lot of people choose not to wear a hearing aid because it can be just too unbearable. This might change for the better in the future, though. For instance, scientists at University of California are developing a next-generation hearing aid inspired by songbirds that emulates the human ear as realistically as possible.

Was that a chip or a chirp?

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Image credits: Virginia Green (http://virginiagreene.tumblr.com/)

All hearing aids have the same basic parts: a microphone, the tonehook or earhook, the volume control, the on/off switch and the battery door. The microphone picks up sounds and sends them to an amplifier that makes them louder. The hearing aid will make some pitches of sound louder than others, depending on the shape of the hearing loss. But Hearing aids aren’t effective for everyone. Hair cells in the inner ear must pick up the vibrations that the hearing aid sends and convert those vibrations into nerve signals. So, you need to have at least some hair cells in the inner ear for it to work. Moreover, most devices aren’t that well tuned, so must of your environment gets equally amplified – this can drive anyone crazy.

“In a crowded place, it can be very difficult to follow a conversation even if you don’t have hearing deficits,” says UC Berkeley neuroscientist Frederic Theunissen. “That situation can be terrible for a person wearing a hearing aid, which amplifies everything.”

Image your sitting in a crowded bar, at a table with your friends. Despite the racket and rattle around, you have no problem having a conversation with your friends because the human brain and ear work together beautifully to hone in on a particular signal – the rest is just background noise that isn’t processed consciously. With a hearing aid, this sort of differentiation is very difficult. So, the ultimate goal is to build a hearing aid that transmits signals and processes audio much in the way the brain would.

[ALSO SEE] Hearing restored in mice following hair cell regeneration therapy

Humans aren’t the only ones capable of differentiating between audio signals. Among other animals that are very apt at this is the songbird. For the past two years, Theunissen and colleagues have analyzed the brain imagery of songbirds to understand how these can distinguish between the chirp of a mate from dozens if not hundreds of strangers. The team eventually identified the exact neurons involved in this process which tune into a signal and remain tuned indifferent of how noisy the environment is. Theunissen calls this an “auditory spotlight”. Imagine you’re looking for your car keys on the dinner table. You have this particular shape, texture and colour that you’re searching for among plates, breadcrumbs and cats. In a similar way to the eye, the ear searchers and finds particular pitches and frequencies – say the voice of your friends at the bar.

“Our brain does all this work, suppressing echoes and background noise, conducting auditory scene analysis,” Theunissen says.

The “auditory spotlight” process has been reproduced in an algorithm, and now the UC team is working with a company to test whether the company can improve performance if installed on conventional hearing aids. This next generation of hearing aids will detect the features of the signal and separate it from any background noise. Unlike a traditional hearing aid, it will have a variable gain so that signal sounds get a boost without distortion, while background sounds are attenuated without being completely muffled out.

“This hearing aid should not eliminate all of the noise or distort the signal,” Theunissen says. “That wouldn’t sound real, and the real sound is the most pleasant and the one that we want to hear.”