For several decades damage from noise-induced hearing loss has been monitored using threshold sensitivity measurements recorded on the conventional pure tone audiogram; and more recently, measuring damage to the delicate outer hair cells in the cochlea using otoacoustic emissions. However, new research into noise-induced cochlear synaptopathy — which by insidiously causing auditory dys-synchrony places it squarely in the auditory neuropathy spectrum disorder (ANSD) “spectrum” — threatens to up-end everything we know about noise-induced hearing loss measurement and treatment due to the temporal resolution damage it silently causes to speech discrimination, while barely affecting threshold measurements. In an upcoming article, we’ll lay out how this new information affects the diagnostic tools the clinician uses, and the technologies recommended.
July 2018 Update: Two weeks after we published this article, crackerjack audiologist Doug Beck published Invisible Hearing Loss:9
…Invisible hearing loss (IHL) refers to people who present with essentially normal hearing acuity (as demonstrated by their pure tone thresholds) and who present with listening disorders (including auditory neuropathy spectrum disorder, spatial hearing disorders, auditory and other processing disorders, attention disorders…). In many respects, IHL acknowledges that hearing and listening occur in the brain (not the ear) and there are a multitude of hearing and listening disorders in which the peripheral auditory nervous system presents as normal.
In my opinion, the audiogram is an excellent tool to understand someone’s ability to hear (limited) pure tones and to reflect a small portion of hearing ability. However, the audiogram is a poor measure and an insufficient “gold standard” to reflect or estimate listening ability (i.e. making sense of sound10 [Emphasis added ~DLS]. Indeed, people who present with normal (or nearly normal) audiograms are often dismissed with not much more than a brief discussion about “the good news is your hearing is normal…” and “preferential seating” and “better lighting” and other apparently reasonable strategies which in isolation, fail to address or incorporate a 21st century understanding of how humans hear and listen.
However, for many children and adults with normal hearing, invisible hearing loss may be (and often is) present in tandem with normal audiograms. That is, if we were to test deeper and challenge the entire auditory system (two ears and the brain working together as a true binaural system) in realistic acoustic environments, we might (more often) detect auditory neuropathy spectrum disorder11 (ANSD) [Berlin et al reference added ~DLS], and/or auditory processing disorders (APDs) and/or spatial hearing disorders (SHDs) — all of which (most often) co-exist with normal hearing.10
July 2018 Comment on Doug’s statement: The conventional definition of auditory neuropathy spectrum disorder11 generally does not include “hidden hearing loss,” as the typical adult-onset auditory dys-synchrony presents itself on the conventional pure tone audiogram as “pseudo thresholds” of 20 to 60 dBHL, even though the unsynchronized X‘s & O‘s jotted down do not convey the profoundness of the loss, i.e. the lack of information content in the scratchy sound conveyed to the patient.12 [UK NHS CI Centers: Pay Attention to this!]
However, as we made the case two weeks before Doug’s 2015 article, we at The Hearing Blog believe that the “Invisible Hearing Loss” manifestation of noise-induced cochlear synaptopathy falls squarely into the auditory dys-synchrony portion of the ANSD “spectrum” as the source of the lesion produces what we identified as lag-only cyclic phase jitter — Please see figure 2 and Reference 7.
And now, back to our original 2015 article:
Noise-induced cochlear synaptopathy is the loss of neural firing synchrony causing loss of temporal resolution at the dorsal cochlear nucleus because of excitotoxic synaptic damage at the inner hair cell — spiral ganglion synapse, with subsequent gradual neural degeneration occurring, adversely affecting fine speech structure decoding hence speech perception, especially in noise.1 And Yes, this puts this form of noise-induced hearing damage squarely inside the ANSD “spectrum” (called until 2008 auditory neuropathy/dys-synchrony (AN/AD)).2 Now at this point, your eyeballs are probably starting to glaze over and you’re wondering what this all means.
Harvard Medical School professor Sharon G Kujawa writes in Putting the ‘Neural’ Back in Sensorineural Hearing Loss:1A, 1B
…Recent work in noise and aging, however, has revealed a much more insidious process that progressively interrupts [synaptic] communication between sensory hair cells and auditory neurons, ultimately leading to death of the neurons themselves. These neurodegenerative changes are likely very common, occurring even in ears with normal threshold sensitivity and a full complement of hair cells [Emphasis added]. As a result, they challenge our traditional approaches to diagnosis and management.
The inner hair cell–cochlear nerve fiber synapse is the primary conduit through which information about the acoustic environment is transmitted to the auditory nervous system. In ears that age normally—without noise exposure, for example—synapses are lost gradually throughout life. Such losses are seen in the cochlea long before the age-related decline of threshold sensitivity or hair cells.3
Noise produces similar, but immediate, synaptic losses and then accelerates aging, even for exposures that produce reversible threshold shifts and no hair cell loss.4, 5A, 5B
A good way of looking at what happens to the neural firing synchrony is to relate it to signal jitter;6A or a bit more closely, cyclic phase jitter,6B which are “rapid, repeated phase perturbations that result in the intermittent shortening or lengthening of signal elements,” which in the case of cochlear synaptopathy is lengthening only, as you can see in the grey arrows, which yield a lower and longer action potential (AP) on the electrocochleogram (ECochG), and hence ABR wave I:
The questions for researchers to answer become:
- What exactly does this noise-induced cyclic phase jitter sound like;
- What is the demonstrable effect on speech perception in quiet and in noise;
- And, how do we measure it?
On this last item, in private correspondence between your humble editor, Prof Kujawa, and our friend Prof Brian CJ Moore at Cambridge, synaptopathic damage that occurs not severe enough to appear on the pure tone audiogram may still be detected on the threshold equivalent noise (TEN) test, but only at a level of TEN thresholds elevated by maybe 5 dB; and importantly, below the 10 dB elevation to diagnose a cochlear dead zone.
Professor Kujawa sounds the alarm in her final 3 paragraphs:
These sobering findings have important implications for public health. One question is, once an ear has been exposed to noise, can the noise insult influence future changes in the ear and hearing, such as those that accrue with age?
Traditionally, the focus has been on thresholds, and an absence of delayed threshold shifts after exposure has been taken as evidence that noise effects will not occur later. Recent work using powerful new tools provides clear evidence that delayed effects can happen, though.
The current goal of federal noise exposure guidelines aims to protect against permanent threshold shifts, assuming that reversible threshold shifts are associated with cochlear recovery and a safe exposure. Accumulating evidence suggests that this assumption is unwarranted.
In order to clarify what damage occurs where and the effects, we have taken Figure 1A from Review of Hair Cell Synapse Defects in Sensorineural Hearing Impairment 7 and annotated it:
For more on the “nuts and bolts” please see Perspectives on Auditory Neuropathy: Disorders of Inner Hair Cell, Auditory Nerve, and Their Synapse.7
Also, from Review of Hair Cell Synapse Defects in Sensorineural Hearing Impairment:8
Abstract/Objective: To review new insights into the pathophysiology of sensorineural hearing impairment. Specifically, we address defects of the ribbon synapses between inner hair cells and spiral ganglion neurons that cause auditory synaptopathy.
Noise-Induced and Age-Related Hearing Loss
Recent findings indicate that cochlear synaptic mechanisms may contribute to these 2 most common forms of hearing impairment. Changes in synapse number and structure have been implied in noise-induced and age-dependent hearing loss. Interestingly, a human association study suggests polymorphisms in the gene coding for the metabotropic glutamate receptor mGluR7 to contribute to susceptibility for age-dependent hearing loss. Excitotoxic synaptic and neural damage is a key candidate mechanism for noise-induced and age-dependent hearing loss (Fig. 5A). It may result from excessive presynaptic release of glutamate, which has long been discussed for noise-induced hearing loss (see below) and has recently been implied for a human progressive hearing loss caused by mutations in the gene GIPC3. Susceptibility to excitotoxic damage could also arise from abnormally high numbers or sensitivity of postsynaptic glutamate receptors, alterations of efferent innervation and from interference with glutamate uptake, 5 but the relevance of these mechanisms for human disease has not yet been demonstrated.
Excitotoxic synaptic damage due to excessive presynaptic release of glutamate has long been indicated to contribute to noise-induced hearing loss. Immunohistochemical quantification of ribbon synapse number has now been used to establish the loss of ribbon synapses during noise exposures. Strikingly, even noise exposures that caused only temporary threshold loss were accompanied by a permanent loss of approximately 50% of the hair cell synapses and subsequent slow degeneration of spiral ganglion neurons in the high frequency region of the cochlea (Fig. 5C, D, F, G). The morphologic damage was reflected by a reduced spiral ganglion compound action potential. Measured as Jewett wave I of the auditory brainstem responses, a permanent reduction was found (Fig. 5E), despite full recovery of the physiologic threshold (Fig. 5B). One possible hypothesis explaining this discrepancy of functional findings is that the noise-induced insult hits the low-sensitivity spiral ganglion neurons, which signal loud sounds, but spares the high-sensitivity neurons, which are responsible for sound perception near threshold. This hypothesis can well explain the finding of poor speech recognition in noisy background. Not surprisingly synaptic insult occurs also during noise exposures that cause a permanent threshold increase.5
Current research aims to understand the presynaptic and postsynaptic changes that occur during noise damage. Moreover, studies explore the reasons why excitotoxic synapse loss is not followed by de novo synapse formation during the weeks after the insult when the disconnected inner hair cells and spiral ganglion neurons are still present. The extent, irreversibility, and functional consequences of excitotoxic synapse loss had not yet appreciated and now require studies of the relevance of this disease mechanism for human noise-induced hearing loss. If comparable to the animal findings, which is likely the case, noise exposure is much more dangerous than we have assumed. We will then have to acknowledge that noise induces synapse and progressive neuron loss and thereby impairs speech reception in noisy environments. We will need to revise noise exposure guidelines, diagnostic procedures and clinical evaluation of occupational hearing loss. In summary, excitotoxic synaptic damage is likely a disease mechanism of noise induced and possibly also of age-dependent hearing loss.
To cap it off, authors Predoehl, Moser, and Starr conclude on the first page:
Abstract/Conclusion: Hair cell ribbon synapses are highly specialized to enable indefatigable sound encoding with utmost temporal precision. Their dysfunctions, which we term auditory synaptopathies, impair audibility of sounds to varying degrees but commonly affect neural encoding of acoustic temporal cues essential for speech comprehension. Clinical features of auditory synaptopathies are similar to those accompanying auditory neuropathy, a group of genetic and acquired disorders of spiral ganglion neurons. Genetic auditory synaptopathies include alterations of glutamate loading of synaptic vesicles, synaptic Ca influx or synaptic vesicle turnover. Acquired synaptopathies include noise-induced hearing loss because of excitotoxic synaptic damage and subsequent gradual neural degeneration. [Emphasis added] Alterations of ribbon synapses likely also contribute to age-related hearing loss.
Last Minute Addendum:
Connecting The Dots: As our loyal readers know well, we at The Hearing Blog are Big Fans of FM assistive listening systems. [Balance of this section deleted June 14, 2015.]
- A: Putting the ‘Neural’ Back in Sensorineural Hearing Loss, by Sharon G Kujawa PhD; The Hearing Journal: November 2014 – Volume 67 – Issue 11 – p 8; doi: 10.1097/01.HJ.0000457006.94307.97 | Mirror copy
B: AudiologyOnline recorded course #25214: Putting the ‘Neural’ Back in Sensorineural: Cochlear Neurodegeneration in Noise and Aging, presented in partnership with American Auditory Society;
- Management of Individuals with Auditory Neuropathy Spectrum Disorder, by Charles Berlin PhD (2008; Lake Como Conference proceedings. | Mirror copy
- Age-Related Cochlear Synaptopathy: An Early-Onset Contributor to Auditory Functional Decline, by Yevgeniya Sergeyenko, Kumud Lal, M Charles Liberman, and Sharon G Kujawa; The Journal of Neuroscience, 21 August 2013, 33(34): 13686-13694; doi: 10.1523/JNEUROSCI.1783-13.2013. | Mirror copy
- Acceleration of Age-Related Hearing Loss by Early Noise Exposure: Evidence of a Misspent Youth, by Sharon G Kujawa, and M Charles Liberman; The Journal of Neuroscience, 15 February 2006; 26(7): 2115-2123; doi: 10.1523/JNEUROSCI.4985-05.2006 | Mirror copy
- A: Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss, by Sharon G Kujawa, and M Charles Liberman; The Journal of Neuroscience, 11 November 2009, 29(45): 14077-14085; doi: 10.1523/JNEUROSCI.2845-09.2009 | Mirror copy of article
B: Mirror copy of Supplemental Data
- A: Definition of jitter
B: Definition of phase jitter
- Perspectives on Auditory Neuropathy: Disorders of Inner Hair Cell, Auditory Nerve, and Their Synapse, by Arnold Starr, Fan-Gang Zeng, H J Michalewski, and Tobias Moser (2008) | Mirror copy
- Review of Hair Cell Synapse Defects in Sensorineural Hearing Impairment, by Tobias Moser, Friederike Predoehl, and Arnold Starr (2013) | Mirror copy
- Invisible Hearing Loss. American Academy of Audiology Opinion Editorial by Douglas L Beck AuD;
- Douglas L Beck AuD: Issues and Considerations Regarding Musicians, Music, Hearing and Listening. Hearing Review, July 29th, 2014;
- Multi-site diagnosis and management of 260 patients with Auditory Neuropathy-Dys-synchrony (Auditory Neuropathy Spectrum Disorder), by Chuck Berlin, Linda Hood, Ben Russell, Thierry Morlet, et al (2010);
- For a truly frightening simulation of what ANSD sounds like to your child, please listen to this sequence of profound, severe, moderate, mild, and then no ANSD samples created in Chuck Berlin’s lab at Kresge (post-Katrina called LSU Health Sciences Center) and vetted with several unilateral ANSD patients . When you play that sample, if the patient wears hearing aids, use earbuds and turn up the volume all the way — That is their life. [Window opens into your media player for the .MP3 file.]
- If you don’t own Professor Brian CJ Moore’s Threshold Equivalent Noise test CD’s, drop a $72 money order into the mail to him and you’ll have your copy of both versions in about a week;
- AudiologyOnline.com is perhaps the very best resource for audiologists, hearing aid professionals, and the hearing impaired community in general. Their articles and webinars are all free to view (free site registration required); and if you need professional CEU’s their $99 annual “all you can eat” price is the best bargain in hearing healthcare. If you haven’t registered with them yet, here’s the link to do it now;
- We also highly recommend viewing these three AudiologyOnline.com webinars, in this order:
- Linda Thibodeau & Cheryl DeConde Johnson: Wireless Technology to Improve Communication in Noise;
- Jace Wolfe: Cochlear Implants and Remote Microphone Technology;
- Erin Schafer: Use of Wireless Technology for Children with Auditory Processing Disorders, Attention-Deficit Hyperactivity Disorder, and Language Disorders.
- Somebody wrote this line which we stuck on the pasteboard as part of the editing process, as a comment on pure tone audiograms, but Google doesn’t cough up the source: We often measure the wrong things, but we convince ourselves that the precision of the measure is indicative of its diagnostic value. Do any of our readers recognize who wrote this gem?
- The paragraphs quoted from the Hearing Journal have been reformatted to conform to the Chicago Manual of Style notes and bibliography method, moving the references from inline with the body copy text down to numbered footnotes in the References section;