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Loss of Auditory Nerve Fibers Uncovered in Individuals With Tinnitus

A new study from Mass Eye and Ear investigators shows that individuals who report tinnitus are experiencing auditory nerve loss that is not picked up by conventional hearing tests, known as cochlear synaptopathy, which is commonly referred to as “hidden hearing loss.”

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The results from this study provide a better understanding on the origins of tinnitus, or experiencing ringing in the ears and affecting more than one out of 10 adults worldwide, and were published in Scientific Reports in November 2023.

“Beyond the nuisance of having persistent ringing or other sounds in the ears, tinnitus symptoms are debilitating in many patients, causing sleep deprivation, social isolation, anxiety, and depression, adversely affecting work performance, and reducing significantly their quality of life,” says senior author Stéphane F. Maison, Ph.D., CCC-A, a principal investigator at Mass Eye and Ear, a member of Mass General Brigham, and clinical director of the Mass Eye and Ear Tinnitus Clinic.

“We won’t be able to cure tinnitus until we fully understand the mechanisms underlying its genesis. This work is a first step toward our ultimate goal of silencing tinnitus,” Maison continues. The paper’s coauthors include 2018 Emerging Research Grants (ERG) scientist David Jung, M.D., Ph.D.

Many individuals with hearing loss report a buzzing, humming, ringing, or even roaring sound in their ears. It’s been a longstanding idea that these symptoms, known as tinnitus, arise as a result of a maladaptive plasticity of the brain. In other words, the brain tries to compensate for the loss of hearing by increasing its activity, resulting in the perception of a phantom sound, or tinnitus. Until recently though, this idea was disputed as some tinnitus sufferers have typical hearing test results.

However, the discovery of cochlear synaptopathy in 2009 by Mass Eye and Ear investigators, including Hearing Health Foundation board member Sharon Kujawa, Ph.D., brought back to life this hypothesis as it was evidenced that patients with typical hearing can have a significant loss to the auditory nerve.

In view of this paradigm shift in the way researchers and clinicians think about hearing loss, Maison and team sought to determine if such hidden damage could be associated with the tinnitus symptoms experienced by a cohort of typical hearing participants.

By measuring the response of their auditory nerve and brainstem, the researchers found that chronic tinnitus was not only associated with a loss of auditory nerve but that participants showed hyperactivity in the brainstem.

Animal studies show the middle ear muscle reflex (MEMR) may be a good way to measure hidden hearing nerve damage, since this reflex especially relies on low-threshold nerve fibers. These charts show exemplar data from one subject. By gauging middle ear muscle contractions through sound cues, the researchers found chronic tinnitus tied to reduced MEMR sensitivity and strength. This adds evidence that tinnitus involves selective damage of low-threshold nerve fibers important for driving the MEMR. Credit: Vasilkov et al./Scientific Reports

“Our work reconciles the idea that tinnitus may be triggered by a loss of auditory nerve, including in people with [typical] hearing,” Maison says.

In terms of future directions, the investigators aim to capitalize on recent work geared toward the regeneration of auditory nerve via the use of drugs called neurotrophins. “The idea that, one day, researchers might be able to bring back the missing sound to the brain and, perhaps, reduce its hyperactivity in conjunction with retraining, definitely brings the hope of a cure closer to reality,” Maison adds.

This is adapted from a Mass Eye and Ear press release. This work was supported by a grant from the National Institute on Deafness and Other Communication Disorders (P50 DC015857) and the Lauer Tinnitus Research Center at Mass Eye and Ear.

The paper’s coauthors include past Emerging Research Grants (ERG) scientist David Jung, M.D., Ph.D., whose 2018 project plan was titled “Mechanisms and development of novel small molecule treatments for cochlear synaptopathy.”

In addition, HHF board member Sharon Kujawa, Ph.D., a 1999 ERG scientist and a member of HHF’s Council of Scientific Trustees, presented on hidden hearing loss for HHF’s April 2022 research webinar.


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