Lost in the Midst People with “hidden” hearing loss can ace a standard hearing test but still struggle to hear in a noisy room. The search is on to better understand it—and diagnose it. Features
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Features  |   July 01, 2017
Lost in the Midst
Author Notes
  • Haley Blum is a former writer/editor for The ASHA Leader. hblum@asha.org
    Haley Blum is a former writer/editor for The ASHA Leader. hblum@asha.org×
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Hearing Disorders / Features
Features   |   July 01, 2017
Lost in the Midst
The ASHA Leader, July 2017, Vol. 22, 48-55. doi:10.1044/leader.FTR1.22072017.48
The ASHA Leader, July 2017, Vol. 22, 48-55. doi:10.1044/leader.FTR1.22072017.48
For something so out-of-sight, so undetected for so long, hidden hearing loss is turning out to be, well, kind of a big deal.
The more technical term for the condition is cochlear synaptopathy, and it’s associated with difficulty understanding speech in noisy environments. Its discovery less than a decade ago has launched labs across the globe into action, as researchers try to understand more about this condition in animals and, hopefully, humans. For good reason, too—if hidden hearing loss is as prevalent in humans as it’s been observed in animals, it could permanently change the way audiologists assess and think about hearing loss.
But there’s an issue: Standard pure-tone audiometry does not pick up this type of hearing loss (that’s where “hidden” comes in). So what can?
That, of course, is the “million-dollar question,” says Sharon Kujawa, associate professor of otolaryngology at Harvard Medical School and director of audiology research and senior scientist at Massachusetts Eye and Ear’s Eaton-Peabody Laboratories.

Patients with hidden hearing loss are likely to struggle with understanding conversation in a noisy environment.

Uncovering what’s ‘hidden’
Even with the research still in its infancy, Kujawa says, hidden hearing loss (HHL) warrants the attention of audiologists now.
The classic view of sensorineural hearing loss has focused on inner-ear hair cells as the primary targets of noise exposure, causing threshold elevation visible on an audiogram. The neurons connecting the hair cells to the auditory nerve had been thought to die largely as a secondary result of hair-cell degeneration.
But a 2009 landmark study in the Journal of Neuroscience by Kujawa and her colleague Charles Liberman threw this notion into question. The team found in mice that loud noise exposure—even though it caused only a temporary threshold shift that kept hair cells ultimately intact—could permanently interrupt their synaptic communication with cochlear neurons. Kujawa and Liberman speculated the loss could contribute to speech-in-noise difficulties and might cause changes that result in abnormal perceptions like tinnitus and hyperacusis.
Suddenly, it was apparent that temporary thresholds shifts may lead to some not-so-temporary consequences.
The term “hidden hearing loss” itself was coined two years later, in another Journal of Neuroscience paper, by Roland Schaette and David McAlpine. In patients, HHL is thought to present as just that—hidden on audiograms, which could mistakenly suggest to audiologists that either there’s no deficit, despite patients’ self-described perceptual issues, or that a patient has another condition such as central auditory processing disorder.
“I’ve heard of too many patients with a normal audiogram who were told, ‘Your hearing is normal. You don’t have any problem,’” says Stéphane Maison, assistant professor of otolaryngology at Harvard Medical School and principal investigator at Eaton-Peabody. “That’s not [always] true.”
Patients with HHL and a normal audiogram are likely to struggle with understanding conversation in a noisy environment—the loss in synaptic connections and fibers of the cochlear nerve terminals is associated with diminished speech-perception abilities. “If you go to a crowded bar or a restaurant … you need those fibers to be able to understand speech in that noise,” Maison says.
It’s not that the audiogram is incorrect in this situation—rather, it doesn’t tell the whole story. Audiograms aren’t sensitive enough to detect the loss of higher threshold fibers, Maison says. “When you measure the audiogram, you estimate the softest sounds the patient can detect. If the patient is missing fibers that will only respond to loud sounds [higher threshold fibers], you can still obtain a normal audiogram.”
So when people who have HHL sit in an audiometric booth listening in quiet, they don’t struggle. (Many audiologists use speech-in-noise tests, but far more do speech testing in quiet.) But, “underneath that audiogram,” Kujawa says, “there can be large variability in the amount of injury to the ear. … You can have massive neural degeneration, massive cochlear synaptopathy, and have normal thresholds.”
That may also be one reason, she adds, that two people with the same audiograms can differ so dramatically in their perception of how difficult listening is.
Maison says audiologists, including himself, can’t dismiss patient concerns that don’t seem to match the audiogram. “If a patient comes to you, it’s because there is an issue,” he says. “Audiologists know how important it is to listen.”
HHL is also “hidden” in the sense that these synapses are not visible through standard light microscopy; uncovering their loss has required new immunostaining and quantification techniques. And it’s impossible to directly observe synaptic changes in any living being’s temporal bones, which house the inner ear, until after death.
But from animal models, researchers have learned that noise exposure may speed up a process that otherwise gradually proceeds with age. “You can lose 50 percent of your synapses in minutes after a noise exposure, but it might take you a full lifetime to lose that number with aging,” says Kujawa.
The synapses “actually seem to be more vulnerable to the aging process and to noise exposure than the sensory cells themselves, which was a pretty big surprise,” says Naomi Bramhall, a researcher at the National Center for Rehabilitative Auditory Research within the Department of Veterans Affairs (VA) in Portland, Oregon, where she focuses on HHL. But “until we have a good way of determining who exactly has loss of synapses and who doesn’t, it’s hard to say exactly what the perceptual consequences are.”

“You can lose 50 percent of your synapses in minutes after a noise exposure, but it might take you a full lifetime to lose that number with aging.”

A search for diagnostics
As researchers tackle HHL-related topics across the spectrum, the search for a way to diagnose the condition in humans is one of the most pressing. Because if the standard audiogram isn’t cutting it, what’s an audiologist to do instead?
“There are lots of labs out there looking at these synaptic losses,” Kujawa says, “either in aging or after noise.”
Most studies have been in animal models, and many have looked at wave-I amplitude. Auditory brainstem response (ABR) testing—also commonly used in clinical settings for things such as threshold sensitivity testing and neurodiagnostic evaluations in specific cases—measures wave I. This wave, the first produced in a series, indicates a response from the auditory nerve and can show if neural output from the cochlea is reduced.
In the animal models of noise and aging, Kujawa and her colleagues have shown a strong correlation between wave-I amplitude measurements and the number of surviving synapses.
Another measurement, the SP/AP ratio, is obtained through electrocochleography. It incorporates an initial bump in wave peaks generated by hair cells (known as “summating potential,” or SP) and a wave-I measure of neural response (known as “action potential,” or AP). (The SP/AP ratio might be useful to standardize responses, because absolute amplitudes can vary from person to person.)
A study led by Maison that incorporated the SP/AP ratio introduced hidden hearing loss into mainstream discussion last fall, with write-ups in major publications like The Wall Street Journal. The paper, published in PLOS ONE, further linked difficulty understanding speech in noise to cochlear synaptopathy, this time in human participants.
The researchers split 34 college-age students into two groups (22 studying music at local Boston schools who self-reported higher noise exposure and less use of hearing protection than the control group, and 12 students enrolled in communication sciences and disorders programs). Although both groups passed audiograms with no indication of hearing loss, the musicians were more likely to perform poorly on a speech-in-noise test than the control participants who regularly use hearing protection.
Using an electrophysiological measurement of auditory nerve health, Maison says they also found a “correlation between the difficulty hearing or repeating words in noise and nerve damage.”
In the paper, Maison and his colleagues note that their data suggest that “a combination of ear-canal electrocochleography, high-frequency audiometry and word-recognition tasks can possibly identify the earliest signs of noise damage to hair cells and neurons.”
While Maison and his colleagues work on a larger follow-up study this summer to replicate their results and to try additional tests and controls, definitively identifying cochlear synaptopathy in humans remains challenging.
“The hidden aspects of hidden hearing loss make it really difficult to study in humans,” Bramhall says. “In animal models we look at the temporal bone after life. When they’re no longer alive, we can open up the temporal bone and actually count the number of remaining synapses. Obviously, we can’t do that in humans while they’re alive—we can’t just open up their temporal bone and count those synapses.”
However, based on the research that’s already been completed on animals—all types of them—Kujawa says the evidence points heavily toward the possibility that humans are not immune to the types of hidden hearing loss found in animals.
“We and others have found noise-induced synaptopathy in every mammal we have ever looked for it in,” she says. “It’s been demonstrated in mouse and guinea pig, in rat, gerbil and chinchilla, and even in nonhuman primates. Age-progressive loss of synapses or nerve terminals has been observed in human temporal bones [post-mortem], so it’s very unlikely that humans will be spared from this synaptopathy after noise. The details, of course, are going to vary from one species to another, but the general phenomenon is pretty clear.”
Beyond a reliable diagnosis tool, researchers are also looking a step further to the possibility of the reversal of HHL. With synapses damaged, the cell body of the auditory nerve fiber still may take months—or even years—to die. “That delay is a window of opportunity for treatment,” Kujawa says.

“If a patient comes to you, it’s because there is an issue. Audiologists know how important it is to listen to patients.”

Rethinking what we thought we knew
The Occupational Safety and Health Administration’s (OSHA) permissible exposure level for noise in the workplace is an average of 90 dBA over eight hours—around the level, the hearing industry has generally agreed, that can begin to cause permanent hearing loss.
But based on research about HHL, lower levels of noise seem to cause damage, even if it doesn’t show up as hearing loss on an audiogram. So what are the responsibilities of OSHA and other federal agencies, such as the National Institute for Occupational Safety and Health, for re-evaluating their limits and recommendations?
The answer is already clear to Maison, even though he acknowledges that finding a way to diagnose HHL is necessary before anything will officially change. “Noise is way more dangerous than we thought,” he says. “All those federal guidelines are outdated.”
For Kujawa, the data at least point toward the need to rethink what has previously been accepted as fact.
“We don’t have all the information yet, but I think we know enough at this point to be concerned,” she says. “We know that this injury occurs for a really broad range of exposures, including many exposures that only produce temporary threshold shifts. And we know that the synaptic loss is permanent. So to me, that signals a need for caution.
“Are we going to run out and change the [recommendation] levels tomorrow based on this?” she asks. “No, because we don’t know what is necessary in a human to cause this kind of synapse loss. But, we know a lot. We really need to start re-examining what we think we know.”
However, VA researcher Bramhall points out that, based on her study on veterans and firearm exposure published earlier this year in the journal Ear and Hearing, the situation may not be “as worrisome as we originally thought.”
She says her work suggests that exceptionally loud exposures, like those from blasts and firearms, are the type of high-intensity noises that seem to be the issue. She also cites a February 2017 study by University of Manchester’s Chris Plack and colleagues published in the journal Hearing Research, which looked at wave-I amplitude in humans (ages 18–36) with a wide range of lifetime noise exposure, but found no evidence of decreasing wave-I amplitude with increasing noise exposure.
The Plack study was conducted in England, where firearm use is less than in the United States, so participants were unlikely to have had firearm exposure, Bramhall says. Together, she adds, this study and studies of her own point toward the likelihood that HHL may be associated only with high-level exposures.
“People definitely need to be careful about firearm use,” Bramhall says, “but I’m not sure that we necessarily need to make a lot of changes to our noise exposure regulations.” However, she adds that with firearm use popular in the United States, people need to understand that a single exposure could result in damage that doesn’t show up on a hearing test.
And while the causes and extent of HHL in humans and its implications for public health are still up for debate, the notion that it could soon be time for audiologists to expand their standard assessment arsenal beyond pure-tone audiometry in quiet is less controversial.
Maison predicts diagnosing HHL will most likely involve more than a single test, including speech-perception performance in noise. But for now, predictions and hypotheses are as close to an answer as the researchers have.
In labs working on this problem, it’s important for scientists to keep clinicians in mind as they look to develop diagnostic tools, Kujawa says. “It will be important in the translational process to not only identify the best [identifiers of HHL], but to then develop them into a procedure that someone can implement in the clinic.”
Regardless, says Maison, the more scientists can find out about hidden hearing loss, the more audiologists can help patients. And there’s a long road ahead.
“We haven’t solved all the problems,” he says. “There’s always more space to investigate, more discoveries to be made.”
Hearing Research Symposium Debuts at 2017 ASHA Convention

Hidden hearing loss is the focus of two sessions at ASHA’s inaugural Research Symposium in Hearing, to be held Friday, Nov. 10, at the 2017 ASHA Convention in Los Angeles.

The symposium has been organized by Ravi Krishnan, professor of speech, language and hearing sciences at Purdue University, who is the hearing and balance science topic chair for the 2017 Convention.

Sharon Kujawa (associate professor of otolaryngology at Harvard Medical School and director of audiology research at Massachusetts Eye and Ear) and Hari Bharadwaj (assistant professor in Purdue University’s Department of Speech, Language and Hearing Sciences) will present on hidden hearing loss. Qian-Jie Fu (director of the Signal Processing and Auditory Research Laboratory at UCLA) will present on the benefits of cochlear implantation for single-sided deafness.

The symposium is open to all convention attendees without separate registration or fee.

1 Comment
July 7, 2017
Shimon Neuman
How is HHL different than APD
This sounds like a classic description of APD, why was the new term HHL coined?
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July 2017
Volume 22, Issue 7