20Q: Tinnitus and Hyperacusis - Reassessment of an Old Problem

From the Desk of Gus Mueller

Any of you who see patients regularly are very familiar with the complaint of tinnitus.  Roughly 10-15% of adults experience tinnitus, and the prevalence is considerably higher for older individuals and those who have been exposed to noise.  Even if you don’t see patients, you probably know someone who has tinnitus, or you may have it yourself.

The suggested cures for tinnitus are almost as numerous as the people who have it.  For example, a Google search on “home remedies for tinnitus” reveals over 400,000 results!  In order to treat our patients with tinnitus, we have to understand its origins.  The notion of a poor dying outer hair cell voicing its last cry for help might make an interesting story for our patients, but our counseling probably should be based a little more on research evidence.  Fortunately, there is exciting research in this area that has been emerging in recent years, and we have an expert to tell us about it in this month’s 20Q.  

Richard Salvi, PhD, is Distinguished Professor in the Department of Communicative Disorders and Sciences at SUNY Buffalo.  Dr. Salvi is co-founder—and continues to serve as director—of UB’s Center for Hearing and Deafness, one of the nation’s foremost hearing research groups.

Dr. Salvi has published more than 300 articles in the leading professional journals, is a member of numerous editorial boards, serves on the boards of national and international organizations, and has been named a Fellow of the Acoustical Society of America. Over the years his research has involved the study of noise and ototoxic drug-induced hearing loss, inner-ear physiology, central auditory plasticity and reorganization, hair cell regeneration and the use of stem cells to treat hearing loss.  His recent research efforts have provided new insights into how tinnitus and the sometimes co-occurring hyperacusis might develop and be sustained.  In this month’s 20Q, Dr. Salvi discusses his findings suggesting that the neural network responsible for tinnitus is considerably more expansive than we have previously believed. 

Finally, I do have to mention that Dick and I attended undergraduate classes together at NDSU in the late 1960s—Go Bison.  One glance at his resume, however, clearly shows that he got a lot more out these classes than I!
 

Gus Mueller, PhD
Contributing Editor
February 2016

 

To browse the complete collection of 20Q with Gus Mueller CEU articles, please visit www.audiologyonline.com/20Q

 

20Q: Tinnitus and Hyperacusis - Reassessment of an Old Problem
 

Richard Salvi

1.  I seem to be hearing more and more about tinnitus research.  Is there really that much more to learn?

It’s certainly true that tinnitus has been studied for some time, but yes, there still is much more to learn and much that we already know, but perhaps forgotten.  Patients with tinnitus react in a complex manner involving many brain regions with different functions.  The brain networks responsible for tinnitus and their relative weights create unique characteristics for each patient.  The better we understand this relationship, the better we can offer assistance and treatment strategies.

2.  You mention brain networks, but aren’t there some basic categories of tinnitus that clinicians encounter?

Yes, there are, but often clinicians fail to investigate.  At the most basic level, it is important to distinguish between objective tinnitus and subjective tinnitus.  In cases of objective tinnitus, an acoustic signal generated somewhere in the body is causing the patient to hear an unwanted sound.  Objective tinnitus is often caused by turbulence in a blood vessel that is propagated and picked up by the ear; the pulsation are synchronized with the heart rate and a stethoscope can sometimes be used to grossly locate the source.  In other cases, a clicking sound is heard caused by rapid myoclonus contractions of the soft palate or middle ear muscles.  In rare cases, patients have spontaneous otoacoustic emissions that we can hear.  At the other end of the spectrum, subjective tinnitus encompasses cases in which there is a phantom auditory sensation in the absence of an acoustic signal. 

3.  How common is subjective tinnitus?

Roughly 12% of adults experience subjective tinnitus, but it is the 1% with troubling and disruptive tinnitus that seek treatment from an otologist or audiologist that have been the focus of much clinical and scientific study.

4. Are there specific events that trigger or provoke subjective tinnitus?

There are several, which again adds to the complexity.   Surveys indicate that there is an upsurge of tinnitus as individuals age, with a high prevalence among those 40 years or older.  Since most of these individuals have some hearing loss, age-related hearing loss seems to be a trigger or causal factor, but since many individuals in that age range often acquire other health problems (e.g., diabetes), age-related hearing loss per se may not be the sole factor.  Tinnitus frequently appears immediately after an intense noise exposure.  In cases such as this where there is an immediate tinnitus onset, the hearing loss in the noise-damaged ear is considered the likely trigger or causal event. However, in the case of repeated exposure to low-level noise, the tinnitus may suddenly emerge months or many years after the exposure.  In this example, tinnitus could be due to age-related hearing loss, noise-exposure, the combination of the two or other comorbid health difficulties.

5.  I’ve certainly seen many tinnitus patients with the noise-induced history.  What about tinnitus following certain drug use? 

Tinnitus often develops after a prolonged course of treatment with certain ototoxic drugs such as cisplatin and aminoglycoside antibiotics that damage the sensory hair cells and neurons in the cochlea.  In cases, such as this tinnitus emerges along with hearing loss a few weeks after the start of therapy.  While cochlear hearing loss is likely a major contributing factor, the systemic toxicity of these drugs (e.g., nephrotoxicity, systemic inflammation) could be significant contributing cofactors.  High doses of aspirin (active ingredient is acetylsalicylic acid), once commonly used to treat rheumatoid arthritis, causes rapid onset of tinnitus and cochlear hearing loss, but since aspirin, a pain reliever, readily crosses the blood-brain barrier it most likely exerts numerous effects on the CNS.

6.  Are there other disorders, factors or non-ototoxic drugs associated with tinnitus?

Yes, this list of conditions is long.  Tinnitus is associated with Meniere’s disease, multiple sclerosis, diabetes, head trauma, middle ear disorder, vestibular schwannomas, temporal mandibular joint disturbances and a host of other medical conditions.  Many therapeutic drugs that do not cause hearing loss have been linked to tinnitus, although in most cases the percentage of individuals that are affected is very low (e.g., antidepressants, antimalarial drugs, NSAID and steroids).  While the rush to judgment is to presume that hearing loss triggers or causes tinnitus, this assumption is clouded by the fact that many individuals with hearing loss do not experience tinnitus.  Like an “and gate” in a computer circuit, the onset of tinnitus may require hearing loss plus some other factor(s).  Tinnitus is likely a multifactorial disorder making it difficult to understand and treat. 

7. If a patient has subjective tinnitus, how can one characterize the phantom sound?

Like many other clinical disorders, subjective tinnitus expresses itself in many forms, although there seem to be some common features.  Because of their experiences with real sounds, patients are able to provide verbal descriptions of their phantom sensations.  Subjective tinnitus is often labeled as a ringing, buzzing or hissing sensation although the spectral and temporal features can be more complex, sounding like chips or cicadas.  Tinnitus loudness varies; in some cases, it is described as loud and intrusive while others describe it as moderately loud or barely audible.  Some patients with hearing loss claim their tinnitus originates within their damaged ear, a feature reminiscent of phantom limb pain.  However, others localize their tinnitus within, or less commonly outside the head.  The tinnitus features remain constant in some individuals while in others the loudness and spectral features change over the course of the day or between days and weeks.  The between-subject diversity suggests that subjective tinnitus is a very complex neurological problem, that likely does not have a singular characterization.

8. How would you suggest that I evaluate a patient’s tinnitus?

There are some relatively straightforward methods that can be used.  If a patient has tonal tinnitus in one ear, you can present a series of different frequencies or narrow band noises to the opposite ear and ask the patient which stimulus most closely matches the tinnitus pitch.  The procedure could be modified so that the sound is presented to the same ear as the tinnitus is perceived in.  In most cases, the tinnitus pitch is matched to a real tone located in the region of hearing loss or near the edge of the hearing loss. The next step would be to ask the patient to match the intensity of the sound to their tinnitus.  If the sound is presented at the tinnitus frequency, then the intensity of the matching sound is typically 5-15 above threshold (5-15 dB SL) in the tinnitus ear.  If the tinnitus pitch is located in the region of hearing loss, say 60 dB HL, the intensity may be quite high, 65-75 dB HL.  If the patient consistently matches the frequency and intensity of the external stimulus to the pitch and loudness of their tinnitus, then the clinician can be fairly confident that the patient has tinnitus.  Such information is important in compensation and legal cases.

9.  What about using masking?

That also can be used to provide additional information.  In the simplest case, you can determine the intensity of a broadband noise that is needed to mask or cover up the patient’s tinnitus, the so-called minimal masking level (MML).  Generally, the noise is increased in the ipsilateral ear in small steps (e.g., 2 or 5 dB) until the patient reports that the tinnitus is no longer audible.  In many cases, the tinnitus can be masked by relatively low-intensity maskers.  In patients such as this, a masker, or a hearing aid that includes masking signals or sound therapy generator, would like to be an effective treatment option. 

10. If there is a moderately severe hearing loss in the tinnitus ear, the use of a high-level masker could be problematic? Any recommendations? 

In normal hearing listeners, it is difficult to mask a real sound presented to one ear with a masking sound presented to the opposite ear.  So you might think that unilateral tinnitus might be difficult to suppress by presenting a sound to the opposite ear.  However, in many cases relatively low-intensity maskers presented to the contralateral ear can suppress tinnitus.  Surprisingly, low-intensity maskers presented to the better ear are sometimes effective in suppressing tinnitus in the opposite ear with severe or profound hearing loss.

11. You indicated that most patients with tinnitus have hearing loss.  What if the patient has tinnitus, but clinically normal hearing?

I have had many 60-70-year-old tinnitus patients call me up to tell me that they have high-pitched tinnitus, but that they have completely normal hearing.  When I hear this, I immediately suspect that the patient has a hearing loss above 8000 Hz, frequencies often overlooked with the conventional clinical audiogram.  More often than not, when these individuals are re-tested over the full range of hearing, they are found to have an elevated threshold between 10-16 kHz; thresholds in this frequency region are typically quite high.  When tinnitus pitch matching is subsequently carried out, the matching frequency is generally in the 10-16 kHz range.  For tinnitus patients, a recommend testing over the full range of hearing.

12.  What if the patient really does have normal hearing from 125 to 16000 Hz?

The pure tone audiogram and distortion product otoacoustic emission are highly effective tools for detecting threshold shifts associated with outer hair cell damage, probably the most frequent cause of sensorineural hearing loss.  However, these measurements fail to detect cochlear pathologies that are confined to the inner hair cells or type I afferent nerve fibers that make synaptic contact with a single inner hair cell.

13.  Confined to the inner hair cells?

Yes, here is an example.  A few years ago, Dr. Lobarinas and I measured pure-tone audiograms in chinchillas that had been treated with carboplatin, an anticancer drug that selectively thins out and destroys the inner hair cells and type I neurons in this species (Lobarinas, Salvi, & Ding, 2013).  Despite the massive loss of inner hair cells and type I nerve fibers, all of the outer hair cells were present and functionally intact.  When we measured the pure-tone thresholds, we found virtually no hearing loss in these animals until the inner hair cell lesions exceeded 80-85%.  The pure-tone audiogram was abysmal at detecting damage to the IHC and type I auditory nerve fibers. Other reports out of the Liberman and Kujawa lab (Kujawa & Liberman, 2009) show that certain noise exposures that cause ~50 dB temporary threshold shifts can cause the type I afferent terminals that connect to inner hair cells to slowly degenerate leading to the subsequent degeneration of a large number of spiral ganglion neurons.  Otoacoustic emissions and ABR thresholds in these rodents are relatively normal, but the wave I amplitude of the ABR is greatly reduced due to the loss of type I neurons.  Cases such as this are sometimes referred to as “Hidden Hearing Loss” because these sensory-neural pathologies go undetected by the audiogram and otoacoustic emission.

The take-home message here is that the audiogram, otoacoustic emissions and later component of the ABR fail to detect damage to the inner hair cell-type I neural pathway.  The absence of hearing loss does not necessarily mean there is absence of damage to the inner hair cells and type I nerve fibers, pathological changes that could ignite or trigger tinnitus in some patients.

14.  Your comments seem to suggest that the neural generator for subjective tinnitus is in the cochlea?

That certainly was the prevailing opinion in the past; since many patients localized their tinnitus to the damaged ear, this assumption seemed plausible.  However, a number of clinical and scientific observations have challenged this view.  First, tinnitus perceived in one ear is often easily masked by stimuli presented to the opposite ear, a finding at odds acoustic masking patterns (i.e., central masking).  Second, tinnitus is a common symptom in the ear of patients with a vestibular schwannoma pressing on the auditory nerve. During surgical removal of the tumor, the auditory nerve is sometimes completely severed.  Despite the fact that the cochlea is no longer connected to the brain, tinnitus persists or worsens in many of these patients.  Third, electrophysiological recording from the auditory nerve of animals with large inner and outer hair cell lesions show a large decrease in spontaneous activity, i.e., hypoactivity as opposed to the hyperactivity that was previously predicted. 

15.  Are you saying that the cochlea is not the neural generator for tinnitus?

Collectively, the results I just reviewed suggest that in the majority of cases the neural generator for tinnitus resides in the central nervous system.  The prevailing view is that cochlear damage may induce aberrant neuroplastic changes in the central nervous system that leads to the perception of a phantom sound.  While we once thought that tinnitus originated from spontaneous hyperactivity in the cochlea, the pendulum has swung in the opposite direction and the current view is that the tinnitus generator(s) reside in the brain. 

16. This is not what I learned in graduate school.  When did this viewpoint become popular? 

Evidence in support of a central generator for tinnitus began to emerge in the mid-1990s with advances in human brain imaging.  In 1998, Alan Lockwood and I published a groundbreaking study in which we used PET imaging to identify regions of the brain that were intimately linked to the perception of tinnitus (Lockwood et al., 1998).  In order to recruit patients into our PET brain imaging study, I went to a tinnitus support group meeting in Buffalo to seek volunteers. After telling them about our study, one person at the meeting told me that she could make her tinnitus louder or quieter by moving her jaw, or sticking her tongue out.  My initial reaction was one of disbelief.  However, several more people got up at the meeting and reported that they could do the same thing.  All of sudden I realized that we had a powerful new way to investigate the neural origins of tinnitus.

17.  How did this discovery change your research direction?

Instead of comparing brain images from a group of normal subject versus tinnitus patients, we could compare brain images from the same subject before and after they made an oral-facial movement caused their tinnitus to become louder or quieter, a condition we now refer to as somatic tinnitus.  This within-subject experimental design eliminated many of the experimental confounds such as age, gender and other biological variables that plague between-subject experimental design.  When the subjects in our study made their tinnitus louder or quieter by making an oral-facial maneuver that modulated the person’s tinnitus, we were able to identify aberrant neural activity in the left auditory cortex, right medial geniculate body, and the left hippocampus, part of the limbic system.  The activation we observed in the left auditory cortex suggested that tinnitus was originating in the brain, not the cochlea because when a real sound is presented to the cochlea it activates both the left and right auditory cortex.  The activation we observed in our tinnitus patients was just in the left auditory cortex unlike a real sound passing through the cochlea which would have active both left and right auditory cortex.

18.  Do these findings relate to the Jastreboff tinnitus model?

To some extent, yes.  Because tinnitus often has emotional overtones (e.g., fear, anxiety and depression), Jastreboff (Jastreboff, Hazell, & Graham, 1994) proposed a neurophysiological model of tinnitus that not only included the auditory pathway but also links to the limbic structures such as the hippocampus, a structure implicated in memory of past events (e.g., tinnitus started when I was stressed out) and the location of an object in space (e.g., where is the sound coming from). 

19.  Did you observe any unusual changes in brain activity in tinnitus patients during sound stimulation?

As you maybe know, tinnitus is often associated with hyperacusis, a condition in which moderate intensity sounds are perceived as being intolerably loud.  From this, you might conclude that sound stimulation might provoke greater activity in the central auditory pathway of tinnitus patients than normal hearing controls.  We tested this hypothesis, by comparing brain activation patterns in our patients with somatic tinnitus versus normal controls.  When 2000 Hz, 80 dB HL tone bursts were presented to just the right ear of normal hearing subjects, we observed neural activity in both the left and right auditory cortex and the left medial geniculate. When the same 2000 Hz stimulus was presented to our tinnitus patients, who had normal hearing at 2000 Hz, but moderate hearing loss at the high frequencies, we were surprised to find that our somatic tinnitus patients showed greater neural activity in the left primary auditory cortex and also the left Brodmann area 38, which is implicated in higher order musical processing.  These results indicate that the left auditory cortex responds more robustly to auditory stimulation despite the fact that our tinnitus subjects had high-frequency hearing loss and therefore less neural activity (hypoactive) flowing from the cochlea into the central auditory pathway.  We refer to this condition as Enhanced Central Gain (Auerbach, Rodrigues, & Salvi, 2014), i.e. conditions in which there is hyperactivity in the central auditory pathway in the face of a reduced neural output from the cochlea.

20.  Is somatic tinnitus common or rare in patients with tinnitus?

One of the criticisms of our PET imaging study was that our patients with somatic tinnitus were a special subpopulation and were not representative of the general population of tinnitus patients.  At the time, there were only a few published reports on somatic tinnitus and its prevalence was unknown.  Subsequent prevalence studies by Levine (Levine, 1999) and our group (Pinchoff, Burkard, Salvi, Coad, & Lockwood, 1998; Simmons, Dambra, Lobarinas, Stocking, & Salvi, 2008) showed that somatic tinnitus is the rule rather than an exception.  Roughly 70% of tinnitus patients can make their tinnitus louder or quieter by movements of the head, neck, jaw, tongue, and shoulders.  Many of the somatic tinnitus patients are unaware that they can modulate their tinnitus until you ask them to listen to their tinnitus while moving their jaw, head neck or shoulder. 

That’s amazing.  I would have never guessed that the prevalence of somatic tinnitus was that high.  I’d like to hear more about it, but I just used up my last question. Can we continue this next month?

Most certainly.  See you then.

Editor's note: Read the March 20Q for further discussion with Dr. Salvi on the topic of tinnitus and hyperacusis.

References

Auerbach, B.D., Rodrigues, P.V., & Salvi, R.J. (2014). Central gain control in tinnitus and hyperacusis. Frontiers in Neurology, 5, 206. doi:10.3389/fneur.2014.00206

Jastreboff, P.J., Hazell, J.W., & Graham, R.L. (1994). Neurophysiological model of tinnitus: dependence of the minimal masking level on treatment outcome. Hearing Research, 80(2), 216-232.  Retrieved from https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7896580

Kujawa, S.G., & Liberman, M.C. (2009). Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss. The Journal of Neuroscience, 29(45), 14077-14085. doi:10.1523/JNEUROSCI.2845-09.2009

Levine, R.A. (1999). Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis. Am. J. Otolaryngol., 20(6), 351-362.  Retrieved from https://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=0010609479

Lobarinas, E., Salvi, R., & Ding, D. (2013). Insensitivity of the audiogram to carboplatin induced inner hair cell loss in chinchillas. Hearing Researcg, 302, 113-120. doi:10.1016/j.heares.2013.03.012

Lockwood, A.H., Salvi, R.J., Coad, M.L., Towsley, M.L., Wack, D.S., & Murphy, B.W. (1998). The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity. Neurology, 50(1), 114-120.  Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9443467

Pinchoff, R.J., Burkard, R.F., Salvi, R.J., Coad, M.L., & Lockwood, A.H. (1998). Modulation of tinnitus by voluntary jaw movements. American Journal of Otolaryngology, 19(6), 785-789.  Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9831155

Simmons, R., Dambra, C., Lobarinas, E., Stocking, C., & Salvi, R. (2008). Head, neck and eye movements that modulate tinnitus. Seminars in Hearing, 29, 361-370.