Roland Schaette – r.schaette@ucl.ac.uk
UCL Ear Institute
332 Gray’s Inn Road
London WC1X 8EE
Popular Version of Paper 4pPP8
Presented Thursday afternoon, June 6, 2013
ICA 2013 Montreal
Tinnitus is the perception of a phantom sound, e.g. ringing, whistling or hissing, in the absence of a corresponding acoustic stimulus. Tinnitus is a frequent phenomenon, it is estimated that 5-10% of the population experience chronic tinnitus, and that for 1-2% of the population the symptoms are so severe that their quality of life is greatly reduced.
The exact mechanisms of tinnitus development have not been clarified yet, but several lines of evidence indicate that there is causal relation between hearing loss and tinnitus: The majority of tinnitus patients also have a hearing loss, the prevalence of tinnitus rises with hearing impairment, and tinnitus patients have more hearing loss on average than age-matched people without tinnitus. Also, up to 90% of patients with otosclerosis (a form of conductive hearing loss) experience tinnitus. Moreover, phantom sounds can also develop when hearing loss is simulated through an earplug. In a recent study where 18 normal-hearing volunteers wore an earplug in one ear for 7 days, 14 reported hearing phantom sounds, and 11 perceived a stable phantom sound at day 7. After removing the earplug (“curing the hearing loss”), the phantom sounds disappeared within a few hours (Schaette et al., 2012).
On the one hand, hearing loss might therefore be a major trigger for the development of tinnitus. On the other hand, hearing loss does not always lead to tinnitus; in fact the majority of people with hearing loss do not have tinnitus. The question of which factors determine the development of tinnitus after hearing loss is therefore central to tinnitus research. We have addressed this question in theoretical studies using computer models. An advantage of these models is that we can integrate knowledge about different kinds of hearing loss and of plasticity in the brain, and then theoretically evaluate a variety of scenarios for the development of tinnitus. Our simulations illustrate that hearing loss reduces the activity of auditory nerve fibres and of neurons in the central auditory system. In the central auditory system, such a reduction of neuronal activity could activate a mechanism called homeostatic plasticity. This mechanism stabilizes the mean activity of neurons on long time scales and thus sets the basic operating point of nerve cells, ensuring that they are neither inactive nor too active. When homeostatic plasticity tries to restore neuronal activity to its target level after hearing loss, it increases neuronal response gain, i.e. it makes the neurons respond stronger to input. A stronger response to the remaining input from the auditory nerve boosts activity levels in the auditory brain and can often restore the overall activity to the pre-hearing loss level. However, this compensation comes at a cost, as the overly excitable neurons then also start amplifying neuronal noise, like for example the spontaneous activity of the auditory nerve. It should be noted that a certain level of spontaneous, random neuronal activity is always present in the healthy auditory system. However, this neuronal activity is normally not perceived, but rather represents the neural code for silence. When neuronal gain is pathologically increased after hearing loss to restore normal activity levels, the resulting amplification of meaningless spontaneous input activity can increase spontaneous activity to such a degree that it starts resembling sound-evoked activity. If such a change happens in one of the first stages of auditory processing in the brain, the higher stages might erroneously deduce that a sound is present, leading to the perception of a phantom sound in the absence of a sound source. The model thus demonstrates how hearing loss could lead to tinnitus, and its predictions of tinnitus frequencies from the audiograms of tinnitus patients closely match the patients’ tinnitus pitch matching results.
We have also utilized the model for a detailed evaluation of a variety of different kinds of hearing loss, to study which of them could lead to the development of tinnitus in the brain through the mechanism of homeostatic plasticity. We found that not every kind and pattern of damage to the hearing apparatus triggers the development of tinnitus in the model. It turned out to be important how the mean sound-evoked activity of the auditory nerve, i.e. the input signal to the auditory brain, was altered in comparison to the level of spontaneously active inputs. A significant decrease in the ratio between sound-evoked and spontaneous input activity favoured the development of tinnitus through an increase in neuronal gain in the model. This condition can for example occur for conductive hearing loss, where the hearing apparatus loses sensitivity without any further damage to the neural elements of the inner ear and auditory nerve. Indeed, the prevalence of tinnitus amongst patients with otosclerosis, which is a common form of conductive hearing loss, is extremely high, up to 90% of them experience phantom sounds. Also, more than 60% of the participants of our earplug study (see above) reported phantom sounds while their ear was plugged. Interestingly, such a tinnitus-promoting change in auditory nerve activity can even occur without apparent hearing loss: when we modelled a loss of responsiveness of a fraction of the auditory nerve fibres, a kind of cochlear damage that can occur without an increase in hearing thresholds, as recently demonstrated in mice (Kujawa and Liberman, 2009), the model developed tinnitus activity patterns. This model predictions is consistent with our auditory brainstem response measurements suggesting that this “hidden hearing loss” is present in tinnitus patients with normal audiograms (Schaette and McAlpine, 2011).
The model result that not all kinds of cochlear damage are equally likely to trigger tinnitus suggests that tinnitus might be reduced through specific acoustic or electric stimulation of the auditory system. Hopefully, this will give rise to new tinnitus treatments.
References
(1) Kujawa SG, Liberman MC (2009) Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss. J Neurosci 29:14077-14085.
(2) Schaette R, McAlpine D (2011) Tinnitus with a normal audiogram: physiological evidence for hidden hearing loss and computational model. J Neurosci 31:13452-13457.
(3) Schaette R, Turtle C, Munro KJ (2012) Reversible induction of phantom auditory sensations through simulated unilateral hearing loss. PLoS One 10.1371/journal.pone.0035238.