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Tinnitus
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Tinnitus P J Jastreboff, Emory University School of Medicine, Atlanta, GA, USA
people with tinnitus just experience it without any negative consequences.
ã 2009 Published by Elsevier Ltd.
General Description of Tinnitus Perception Introduction and Definitions Tinnitus is defined as a perception of a sound that is not related to an acoustic source or electrical stimulation of the auditory pathways. As such it is a phantom auditory perception, that is, a perception of a sound without any corresponding vibratory activity within the inner ear. In this respect it is similar to the phenomena of phantom limb and phantom pain. Perception of phantom sound must last for at least 5 min to be classified as tinnitus since more than 90% of the population occasionally experiences a short perception of a phantom sound that disappears within seconds. Somatosounds (sounds produced by a body) are sometimes classified as ‘objective tinnitus,’ in contrast to ‘subjective tinnitus,’ perceived without corresponding sound. Use of this classification has been criticized because detection of somatosound depends heavily on the equipment used. In this article, the term tinnitus is used to denote a phantom auditory perception. Tinnitus is not a disease but a symptom triggered by variety of factors. It seems that in the majority of cases, it is linked to a dysfunction of the periphery of the auditory system, and only in approximately 1% of cases it can be associated with some medical problem. Indirect results, however, suggest that the inner ear (the cochlea) does not directly generate the tinnitus signal. For example, cutting the auditory nerve is not an effective method of alleviating tinnitus, and sometimes the perception of tinnitus does not even change. Moreover, in spite of many years of intensive study, there is no compelling evidence of any specific neuronal activity recorded from the auditory nerve of animals which can be clearly linked to tinnitus. This discrepancy could be explained by discordant dysfunction theory, discussed in the section titled ‘Models of tinnitus.’ It is important to differentiate two subpopulations of people who have tinnitus. For only a small proportion of people with tinnitus is it bothersome and affects their lives, evoking anxiety, annoyance, panic, problems with concentration, sleep, and so forth. Consequently, it is labeled clinically significant tinnitus as these people need professional help. The effects of tinnitus may reach a profound level, to the point of totally controlling patients’ lives and contributing to suicidal tendencies. On the other hand, the majority of
Tinnitus can be perceived as a wide variety of sounds. The most typical descriptions are ringing, hissing, cycads, escaping steam, and roaring. Tinnitus can be intermittent or continuous and may fluctuate in volume or change pitch. It can be perceived in one ear, in both ears, or in the head. The perceived loudness may vary significantly over a period of days. Examples of tinnitus and somatosounds are presented here. The sounds of tinnitus have been recreated by Dr. Jonathan Hazell, who used a musical synthetizer and interacted with patients until patients stated that the synthesized sound is very close to their tinnitus. In addition, a somatosound recorded in the ear canal of a patient and probably caused by jugular venous flow in the middle ear cavity is included, along with a somatosound from a patient diagnosed with palatal myoclonus.
Epidemiology Continuous tinnitus is perceived by 10–20% of the general population, with bothersome tinnitus affecting 3–8%. It is estimated that highly debilitating tinnitus exists in about 0.5% of the general population. Tinnitus occurs in all age groups. Recent data show that prevalence of tinnitus in children is similar to that observed in adults and that when children are bothered by tinnitus, it affects them to the same extent as it does adults. The prevalence of tinnitus perception increases significantly with aging; however, prevalence of the bothersome tinnitus declines for people 65 and older. As prevalence of hearing loss increases systematically with aging and prevalence of bothersome tinnitus decreases for older age groups, this observation argues against a simplistic link between bothersome tinnitus and hearing loss.
Medical Conditions Related to Tinnitus and Somatosounds Traumatic noise exposure, hearing loss, and head trauma are typically associated with tinnitus. The majority of cases of vestibular schwannoma exhibit tinnitus, and for Me´nie`re’s disease, low-pitch roaring, (tinnitus) is an obligatory symptom for diagnosis.
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Tinnitus accompany hyperacusis (defined as abnormally strong reactions to sound occurring within the auditory pathways) is present in more than 85% of cases, and hyperacusis is present in 25–30% of tinnitus cases. It appears that hormonal changes such as those that occur during pregnancy, menopause, or thyroid dysfunction promote tinnitus. Permanent damage of the inner ear typically produces permanent tinnitus, while transient impairment of inner ear function (e.g., resulting from moderate noise overexposure) may yield temporary tinnitus (called ‘disco tinnitus’). A long list of medications presumably inducing tinnitus is widely propagated; however, a critical review of the literature reveals that only aminoglycosides and quinine in high doses, some anticancer drugs, and withdrawal from benzodiazepines evoke tinnitus. Tinnitus could be a first indication of ototoxicity and emerges before hearing loss when patients are treated with ototoxic drugs. Salicylates (e.g., aspirin) reliably induce tinnitus in humans, and salicylates are used in animal models to produce tinnitus. As very high doses are needed to induce tinnitus, aspirin is not a significant factor clinically. Contrary to common belief, there are no clear data proving that any dietary manipulation evokes or relieves tinnitus. Smoking has been associated with increased prevalence of tinnitus, and alcohol in moderation offers some protective effect. Disorders of the somatosensory system (e.g., temporomandibular joint disorder) have been linked with tinnitus. Indeed, many patients can modulate their tinnitus by performing manipulations of the head and neck areas. Moreover, it is possible to evoke short temporal tinnitus by such manipulations in a significant proportion of people without tinnitus. Recent systematic neurophysiological studies have revealed strong somatosensory input to low levels of the auditory pathways such as the ventral and dorsal cochlear nuclei. It is possible to envision chronic tinnitus resulting predominantly from somatosensory input, but the data supporting such a possibility are limited. Currently, somatosensory modulation is used for research purposes (e.g., in imaging studies) as it offers a possibility of time-locked modulation of tinnitus. Somatosounds have a variety of sources. Frequently they are related to the cardiovascular system, typically abnormalities of blood flow in the head area that are pulsatile in synchrony with the heartbeat. Nonpulsatile somatosounds could be related to palatal or middle ear myoclonus or a constantly open eustachian tube, resulting in the perception of air flow over its opening. Another interesting case is the rare perception of spontaneous otoacoustic emissions generated in the inner ear.
Measurements Separate methods are needed for evaluation of tinnitus severity and for delineation of its perception. For tinnitus severity, a variety of questionnaires are used. Psychoacoustic properties of tinnitus are described by pitch match, loudness match, maskability (i.e., minimal level of white noise required to suppress its perception), and postmasking effects (disappearance of tinnitus for a certain time or increase in its loudness). Perceived pitch covers the full range of hearing, and in the majority of cases, tinnitus is perceived in the higher frequency ranges (above 4 kHz). The loudness match determined by psychoacoustic methods is stable for a given patient, disregarding subjective loudness perception. For the majority of patients, tinnitus loudness match is within 15 dB of their hearing threshold for the frequency corresponding to tinnitus pitch. Notably, there is no relation between psychoacoustic characterization of tinnitus and its severity. A number of physiologic measurements have been tried for objective detection of tinnitus. Evaluation of the specifics of cochlear sound transduction, function of the olivocochlear efferent system, spontaneous activity of the auditory nerve, auditory brain stem responses, and late cortical potentials have failed to provide clear correlates with the presence of tinnitus. Substantial progress has been achieved, however, with positron emission tomography, functional magnetic resonance imaging, voxel-based morphometry, and magnetoencephalography. Strongest results were obtained with magnetoencephalography, which demonstrated changes in tonotopic organization of the auditory cortex in frequency areas corresponding to tinnitus pitch match. Furthermore, the extent of tonotopic map modification correlates with subjectively perceived strength of tinnitus. Results of imaging studies regarding activation of various parts of the auditory system have frequently been inconsistent with one other. The majority of these studies, however, have shown significant activation of nonauditory structures, particularly the limbic system. Specifically, the auditory thalamus, various parts of the limbic system, the nucleus accumbens, the reticular formation, and the cerebellum have been shown to have changed activity in relation to tinnitus.
Differentiation between Experiencing Tinnitus and Being Bothered by Tinnitus As tinnitus is a perception of a sound, the auditory system has to be involved. At the same time, there is a lack of correlation between psychoacoustic characterization of tinnitus and its severity or treatment outcome. These observations suggest a need to identify
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two different classes of mechanisms: The first is those mechanisms related to generation to tinnitus-related neuronal activity (referred to, for brevity, in this article as the tinnitus signal) and tinnitus perception, which would be common to all people perceiving tinnitus regardless of whether they have a problem with it. The second class of mechanisms, specific to bothersome tinnitus, addresses the issue of how the tinnitus signal evokes negative reactions in the brain and body, resulting in tinnitus’ being a problem. Potential Generators of Tinnitus-Related Neuronal Activity
There is a consensus that in the majority of cases, the peripheral auditory system is involved in tinnitus generation. There is a small percentage of purely central tinnitus, such as occurs after cutting of the auditory nerve or in cases of auditory imagery or musical hallucinations. On the other hand, there is no consensus regarding other aspects of tinnitusrelated neuronal activity. A dominant view is that tinnitus perception results from detection of an increase of the spontaneous activity within the auditory pathways. There are data, however, strongly pointing out that actually modification in temporal patterns of discharges, specifically bursting activity, is related to tinnitus and that the increase of spontaneous activity is rather linked to hearing loss, which typically accompanies tinnitus. The synchronization of the activity between neurons has been proposed as well, and although absent at the lower level of the auditory system, it might play some role in the auditory cortex. The list of main proposed mechanisms of generation of tinnitus-related neuronal activity covers a wide variety of structures and dysfunctions, including hypoxia and ischemia in the cochlea; abnormal neurotransmitter release from the inner hair cells; abnormalities in transduction processes within the cochlea; damage of the auditory nerve; decreased activity of the cochlear efferent system; somatosensory–auditory interaction; neuronal plasticity, cortical reorganization of tonotopic maps, and hypersynchrony of neuronal discharges; enhanced sensitivity of the auditory pathways after decrease of the auditory input; and discordant damage or dysfunction of outer and inner hair cells. It is expected that for various types of tinnitus, different mechanisms are responsible for tinnitus emergence. Until now none has been proven. While other postulates might be correct, there is growing evidence supporting the last two hypotheses. Until the late 1980s there was no accepted animal model of tinnitus, and it was difficult to validate proposed hypotheses because of inherent limitations
of research on humans. A number of animal models are available now, allowing study of the physiological aspects of tinnitus perception. Enhanced Sensitivity of the Auditory Pathways and Emergence of Tinnitus after Decreased Auditory Input
It is possible to induce temporary tinnitus in a majority of people just by placing them in a very quiet environment. Moreover, tinnitus gets louder under such conditions. One of the mechanisms potentially involved in both these observations is enhanced sensitivity and increased amplification within the auditory pathways after decreased auditory input. Behavioral data argue that the auditory system (as other sensory systems) works as an automatic gain control system, that is, when input signal is low, then amplification increases, and when input signal is higher, then gain of the system is lowered. In an anechoic chamber, participants hear weak, normally unnoticeable sound, such as heartbeat or the movement of clothes caused by breathing, with all these sounds perceived as being quite loud. Recordings of single-unit activity from various centers of the auditory pathways have shown that the sensitivity of the neurons does indeed increase under conditions of low auditory input or when the inner ear is damaged. Opposite behavioral effects are observed when participants are in noisy environments. Enhanced amplification within the auditory pathways may happen as a result of various reasons and evoke or enhance tinnitus or induce hyperacusis. Models of Tinnitus
A challenge to modeling tinnitus is the lack of abundant neurophysiological data and the fact that there are likely to be several types of tinnitus, each generated by a different underlying mechanism. A starting point for models is the apparent paradox of a lack of tinnitus-related activity in the cochlea coupled with the presence of sound perception, pointing to a central origin for the generation of tinnitus. The observation that tinnitus often accompanies hearing loss focuses attention on the central auditory pathway. One simple model would propose that a normal balance of excitatory and inhibitory input to some center in the pathway is disrupted by hearing loss. If the disruption is to the inhibitory input, the resulting excitatory input is unbalanced and could lead to tinnitus. This discordant dysfunction theory has been applied to the dorsal cochlear nucleus, a cochlear nucleus subdivision that has abundant interneurons, many of which are inhibitory. Indeed, experimental evidence in animals shows abnormally high ‘spontaneous’ activity in this center accompanying hearing loss. The particular neural pathways involved remain obscure. The auditory nerve
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does provide two types of input to the dorsal cochlear nucleus: type I fiber inputs from the inner hair cells and type II fiber inputs from the outer hair cells. Inner hair cells are contacted by 95% of afferent fibers of the auditory nerve (which are type I, thick, fast, and myelinated), and these cells act as a transducer, converting the vibration of the basilar membrane of the cochlea into electrical impulses within the auditory nerve. Total deafness occurs if all these cells are damaged, even with untouched outer hair cells. Outer hair cells function as a mechanical amplifier, enhancing vibration for the lower half of the range of perceived sound levels by about 60 dB. It is possible to have normal hearing even if 30% of outer hair cells are damaged. Rapid decrease of their function has been associated with an emergence of tinnitus in humans. They are contacted by about 5% of auditory nerve fibers (type II, thin, slow, and unmyelinated). Outer hair cells are preferentially damaged by intense sound exposure. However, both type I and type II inputs are likely to excite their targets in the brain, and thus further inhibitory interneurons, perhaps to one of these pathways within the dorsal cochlear nucleus, would need to be involved to generate unbalanced excitation. Specifically, the discordant dysfunction theory proposes that when an imbalance of functional properties of outer and inner hair cells occurs, it yields the disinhibition of spontaneous neuronal activity in the dorsal cochlear nucleus, causing a general increase of the spontaneous activity and emergence of bursting, epileptic-like activity, which after further processing within the auditory pathways is perceived as tinnitus. Therefore, while there is no vibratory activity related to tinnitus in the cochlea, the cochlea still may serve as a source of the tinnitus neuronal signal. The Neurophysiological Model of Tinnitus
Disregarding specifics of mechanisms yielding the presence of the tinnitus signal in the auditory pathways, there is consensus that once it is detected, it is perceived as a sound. Little attention has been given to mechanisms involved in converting tinnitus from benign perception of a sound to a significant problem affecting people’s lives. In the past, the dominant approach was through psychology, with no attempt to identify specific neurophysiological structures and mechanisms involved. The neurophysiological model of tinnitus, which attempts to approach tinnitus from the point of view of neuroscience, points out the inherent involvement of the central nervous system (CNS) in tinnitus, and attempts to indicate systems, structures, and the role of specific mechanisms of the brain function in clinically significant tinnitus.
The observation that tinnitus pitch, maskability, and loudness are not correlated at all with tinnitus severity for the population of patients strongly supports the postulate that the auditory system is secondary in clinically significant tinnitus. The neurophysiological model of tinnitus postulates that in the case of bothersome tinnitus, systems other than the auditory system of the brain have to be involved. The limbic and autonomic nervous systems play the major role, and other systems, such as prefrontal cortex and cerebellum, may be involved as well. Furthermore, the model stresses strongly the importance of subconscious processing of the information and the importance of the principles of conditioned reflexes in governing the connections between auditory and other brain systems. Briefly, tinnitus-related neuronal activity which originates in the auditory system starts to activate other brain systems because of both cognitive assessment of tinnitus and subconscious connections created as the result of one of the principles of conditioning. Temporal association of signal (tinnitus) and reinforcement (annoyance, strong emotional upheaval due to any reason) are sufficient to produce this conditioned reflex. Indeed, a study performed to identify factors most frequently linked to the emergence of clinically significant tinnitus revealed that in a majority of cases, it develops as the result of factors totally irrelevant to hearing, such as retirement, losing a job, divorce, and so forth. The diagram of the main systems and connections involved in clinically significant tinnitus is presented in Figure 1(a). In cases when people experience tinnitus but are not bothered by it, only the auditory system is activated. Once tinnitus-related neuronal activity spreads to the limbic and the sympathetic part of the autonomic nervous systems, the new functional connections are created, enhanced, and governed to a large extent by the principles of conditioned reflexes. The autonomic nervous system consists of two reciprocally antagonistic parts, the sympathetic and the parasympathetic systems. Activation of the sympathetic system prepares people for physical or mental action, and activation of the parasympathetic system sets the stage for rest and relaxation. Overactivation of the sympathetic system yields stress, anxiety, panic attacks, and the fight-or-flight reaction. All behavioral reactions exhibited by tinnitus patients, such as anxiety, annoyance, panic, decreased ability to enjoy life activities, problems with attention, and problems with sleep, are consistent with activation of the sympathetic system. When the term ‘autonomic nervous system’ is used in this discussion, it denotes the sympathetic system unless otherwise specified. According to the neurophysiological model of tinnitus, problems
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Auditory and other cortical areas Perception and evaluation (consciousness, memory, attention)
Auditory subconscious Detection/processing
Limbic system Emotions
Auditory periphery Source
Reactions
Autonomic nervous system
a Auditory and other cortical areas Perception and evaluation (consciousness, memory, attention)
HP Auditory subconscious Detection/processing
Limbic system Emotions
HER
Reactions
HAR
Auditory periphery Source
Autonomic nervous system
b Figure 1 The neurophysiological model of tinnitus. (a) The block diagram outlining structures and connections involved in clinically significant tinnitus. The tinnitus signal, typically generated at the periphery of the auditory system, is detected and processed in subconscious pathways of the auditory system and finally perceived at the auditory cortex. If tinnitus is classified as an important negative stimulus, self-enhancing loops, governed by principles of conditioned reflexes, develop. Note existence of two loops: high, involving consciousness, and low, the subconscious loop. (b) Specific functional connections at which habituation of tinnitus occurs. HER, habituation of emotional reactions; HAR, habituation of reactions evoked by the autonomic nervous system; HP, habituation of tinnitus perception. The primary goal of tinnitus retraining therapy is to achieve habituation of reactions; habituation of perception will follow automatically.
arise from proper reaction of the brain to an inappropriate stimulus, that is, the reactions would be appropriate to a life-threatening stimulation, but tinnitus perception results from compensatory action of the auditory system to a situation which does not indicate danger. The activation of the limbic and autonomic nervous systems by tinnitus signal occurs via two pathways: conscious and subconscious, or high and low loops, respectively (Figure 1(a)). The conscious loop involves high cortical areas, perception, cognition, and verbalization. During the process of development of clinically significant tinnitus, this path is created first.
Tinnitus attracts attention, thoughts, concerns, and fears, which activate the limbic and autonomic nervous systems. If these initial thoughts are properly addressed by demystification of tinnitus and its categorization as a neutral stimulus, initial activation of the limbic and autonomic nervous systems is extinguished, and tinnitus does not become a problem. If, however, these thoughts are not addressed properly or, even worse, are enhanced by negative counseling, these connections become stronger, and problems caused by tinnitus are enhanced. The presence of reciprocal connections – signals from the auditory subcortical and cortical areas activating the limbic system and evoking
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(negative) emotions – in turn changes reactivity of the auditory centers, causes enhancement of initial connections, and finally results in establishment of strong reactions of the limbic and autonomic nervous systems. These reactions act as negative reinforcement for a conditioned reflexes arc which links the tinnitusrelated neuronal activity within the auditory system (conditioned stimulus) with reactions. They enhance cognitive concerns as well as further worsening the problem. Note that the outlined processes by definition involve neuronal plasticity. At a subconscious level, the tinnitus signal is going through strong functional connections between the medial geniculate body and the lateral nucleus of the amygdala, which is one of the crucial components of the limbic system. This low loop develops after the high loop, it is governed by principles of conditioned reflexes, and it might become dominant in chronic tinnitus. Therefore, because of the presence of the low loop, the activation of the limbic and autonomic nervous systems might occur even without conscious perception of tinnitus. Notably, a signal conveyed via this route cannot be directly modified by conscious thinking, and a method appropriate for retraining of conditioned reflexes would be more appropriate.
Treatments Treatment of tinnitus is a challenging problem at both the theoretical and the clinical level. Observations of what works and what does not provide some insight into mechanisms of tinnitus. Thousands of years of attempts at treatment (tinnitus was first described in Babylonian clay tablets) have not brought consistently positive results. Only selected treatment methods are outlined. Suppression or Weakening the Tinnitus Signal
The first class of approaches is aimed at suppressing tinnitus perception temporarily (masking) or partially decreasing it. In neurophysiological terms, total suppression of tinnitus perception would mean that detection of tinnitus-related neuronal activity is prevented by providing the auditory system with another stimulation which would make detection of the tinnitus signal impossible. Attempts to apply this method have revealed that clinically relevant suppression of tinnitus perception in practice can be achieved in only a small percentage of cases. Direct stimulation of the auditory nerve via a cochlear implant increases the effectiveness by about 50%, but this method can be used only by the very small proportion of tinnitus patient who are profoundly deaf. Electrical
stimulation applied outside the cochlea has failed to be substantially effective. Direct electrical stimulation of the auditory cortex is under investigation but has failed so far to show superior results. A weakening of tinnitus-related neuronal activity can be achieved via a variety of methods. The simplest, and the most popular, is by enriching auditory background stimulation, and it is implemented in a wide variety of sound therapy. Two neurophysiological mechanisms are bases for decreasing the strength of the tinnitus signal (i.e., tinnitus-related neuronal activity). First, the strength of any signal depends on its difference with background rather than on its absolute physical value. Second, the sensitivity to sensory signals depends on longer-term average input. Consequently, by an increase of the auditory background, the tinnitus signal is decreased due to the combined action of both mechanisms. The type of sound is in this respect secondary; however, it plays a role because of other factors (e.g., ease of habituation, inherent preference for certain sound levels, emotional and cognitive connotations). Another class of treatments attempts to modify the tinnitus signal at the central level rather than by stimulation of the periphery. In addition to direct electrical stimulation of the auditory cortex, transcranial magnetic stimulation has been tried recently. Strong pulses of the magnetic field are applied to the skull outside the cortical area to be stimulated. Magnetic field crosses the skull easily and evokes a strong electrical field in the cortex, which in turn stimulates cortical fibers. The effects on the brain function depend on the frequency of stimulation. High frequency evokes direct inhibitory action on the cortical activity, while low-frequency stimulation appears to induce plastic changes in organization of cortical networks and potentially their interaction with subcortical centers. While it is not clear what specific reorganizations occur, this approach has been shown to attenuate tinnitus. The effects are mild, however, and it is not clear whether they are long lasting. Nevertheless, observation that transcranial magnetic stimulation has some impact on tinnitus supports the importance of the modification of the CNS in tinnitus treatment. Psychological Approaches
Psychological treatments cover a variety of approaches, from simple attempts to distract attention from tinnitus to improved coping and up to behavioral cognitive therapy. Behavioral cognitive therapy seems to be most effective in the class of psychological treatment and is based on the assumption that because thoughts evoke emotions, it is possible by changing thoughts to
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modify emotions evoked by tinnitus. There are wellestablished, effective methods to achieve this goal, and this method is effective in a significant proportion of patients. According to the neurophysiological model of tinnitus, behavioral cognitive therapy nullifies the high loop and therefore decreases stimulation of the limbic and autonomic nervous systems. Medications
Pharmacological approaches have been tried for a long time and, in spite of their lack of success, are still among the most popular. Some medications aim at the periphery of the auditory system, others at the limbic and autonomic nervous systems to decrease anxiety and annoyance and improve coping. Trials of new pharmacological candidates are ongoing, but so far research has failed to show any drug to be consistently effective for tinnitus. Tinnitus Retraining Therapy
All treatment methods presented so far aim at modification of tinnitus perception or signal or alleviation of tinnitus-evoked reactions. Tinnitus retraining therapy (TRT) differs in this respect as it aims to retrain the brain to extinguish specific, tinnitus-related functional connections between the auditory and the limbic and autonomic nervous systems and through this mechanism to decrease or remove tinnitus-evoked reactions (Figure 1(b)). TRT attempts to modify neither the source of the tinnitus signal nor the brain centers involved in reacting to it. As a consequence, TRT is independent of the source of the tinnitus signal (tinnitus etiology) and can be used to treat any type of tinnitus. Briefly, TRT consists of counseling and sound therapy, both strictly based on the neurophysiological model of tinnitus. The goal is to achieve habituation of the tinnitus-evoked reactions, which will be followed automatically by habituation of tinnitus perception (Figure 1(b)). Habituation of reactions is basically identical to the passive extinction of conditioned reactions. TRT uses a modified version of passive extinction of conditioned reflexes in which both the reactions and the stimulus are decreased simultaneously. Habituation of tinnitus can be achieved by a variety of methods. TRT’s approach is easily implemented and works on both the tinnitus and the decreased sound tolerance (hyperacusis and misophonia) that frequently coexists with tinnitus. The role of counseling is to reclassify the tinnitus signal into the category of neutral stimuli, as habituation of any stimulus is difficult when the stimulus has negative connotations and impossible when these associations are very strong. It effectively disrupts the higher loop and decreases stimulation of the limbic
and autonomic nervous systems by cognitive processes. In this respect it is similar to behavioral cognitive therapy but uses a different counseling approach. Sound therapy is the second part of TRT. It aims to decrease the strength of the tinnitus signal through application of a number of guides provided by the neurophysiological model of tinnitus (e.g., use of sound during the night and avoiding annoyance and suppression of tinnitus perception).
Future Goals It has been argued that tinnitus is a phantom auditory perception and should be analyzed from the point of view of neuroscience rather than by ear-oriented (e.g., otolaryngological or audiological) or mind-oriented (e.g., psychological) approaches. Significant progress in understanding mechanisms of tinnitus and its treatment has been achieved in large part because of the shift from earcentric or black-box approaches to neuroscience. A number of important neurophysiological questions remain, however. Significant efforts focus on delineating structures in the brain which are involved in the phenomenon of tinnitus. Imaging studies are consistent in indicating involvement of the limbic system and parts of the brain involved in anxiety, but data from the auditory system are much more variable and unclear. Researchers still debate what tinnitus-related neuronal activity looks like. The dominant belief, that it takes the form of increased spontaneous activity, has been challenged, and it has been proposed that changes in temporal patterns of neuronal dischargers, involving high-frequency, bursting, epileptic-type activity, is in reality a neuronal correlate of tinnitus. There is even less clarity on the neurotransmitters and receptors involved. Gamma-aminobutyric acid, glutamate, serotonin, and other systems, as well as N-methyl-D-aspartate receptors, have been implicated. There are, however, no data proving clear involvement of any of these systems, and drug trials for tinnitus so far argue against a dominant involvement of any of these systems in tinnitus. Due to obvious limits on research on humans, animal models of tinnitus are extremely important. Since the mid-1980s, when the first valid animal model of tinnitus was introduced, a variety of models have emerged, including most recently a model based on prepulse inhibition of the startle reaction. By acknowledging the crucial involvement of the CNS in tinnitus and combining animal and human research, it should be possible to achieve better understanding of this elusive phenomenon and to find more effective methods for its alleviation.
1008 Tinnitus See also: Auditory System: Central Pathway Plasticity; Auditory System: Central Pathways; Auditory/ Somatosensory Interactions; Deafness; Hair Cells: Sensory Transduction.
Further Reading Chen G-D and Jastreboff PJ (1995) Salicylate-induced abnormal activity in the inferior colliculus of rats. Hearing Research 82: 158–178. Eggermont JJ and Roberts LE (2004) The neuroscience of tinnitus. Trends in Neurosciences 27: 676–682. Jastreboff PJ (1990) Phantom auditory perception (tinnitus): Mechanisms of generation and perception. Neuroscience Research 8: 221–254.
Jastreboff PJ, Brennan JF, Coleman JK, and Sasaki CT (1988) Phantom auditory sensation in rats: An animal model for tinnitus. Behavioral Neuroscience 102: 811–822. Jastreboff PJ and Hazell JWP (2004) Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. Cambridge: Cambridge University Press. Jastreboff PJ and Jastreboff MM (2006) Tinnitus retraining therapy: A different view on tinnitus. ORL: Journal for Oto-RhinoLaryngology and Its Related Specialties 68: 23–29. Jastreboff PJ and Jastreboff MM (in press) Tinnitus and hyperacusis. In: Ballenger JJ, Snow JB Jr., and Ashley WP (eds.) Ballenger’s Otorhinolaryngology Head and Neck Surgery, 17th edn., ch. 31. San Diego, CA: Singular Publishing. Snow JB (2004) Tinnitus: Theory and Management. London: BC Decker.
Tinnitus P J Jastreboff, Emory University School of Medicine, Atlanta, GA, USA
people with tinnitus just experience it without any negative consequences.
ã 2009 Published by Elsevier Ltd.
General Description of Tinnitus Perception Introduction and Definitions Tinnitus is defined as a perception of a sound that is not related to an acoustic source or electrical stimulation of the auditory pathways. As such it is a phantom auditory perception, that is, a perception of a sound without any corresponding vibratory activity within the inner ear. In this respect it is similar to the phenomena of phantom limb and phantom pain. Perception of phantom sound must last for at least 5 min to be classified as tinnitus since more than 90% of the population occasionally experiences a short perception of a phantom sound that disappears within seconds. Somatosounds (sounds produced by a body) are sometimes classified as ‘objective tinnitus,’ in contrast to ‘subjective tinnitus,’ perceived without corresponding sound. Use of this classification has been criticized because detection of somatosound depends heavily on the equipment used. In this article, the term tinnitus is used to denote a phantom auditory perception. Tinnitus is not a disease but a symptom triggered by variety of factors. It seems that in the majority of cases, it is linked to a dysfunction of the periphery of the auditory system, and only in approximately 1% of cases it can be associated with some medical problem. Indirect results, however, suggest that the inner ear (the cochlea) does not directly generate the tinnitus signal. For example, cutting the auditory nerve is not an effective method of alleviating tinnitus, and sometimes the perception of tinnitus does not even change. Moreover, in spite of many years of intensive study, there is no compelling evidence of any specific neuronal activity recorded from the auditory nerve of animals which can be clearly linked to tinnitus. This discrepancy could be explained by discordant dysfunction theory, discussed in the section titled ‘Models of tinnitus.’ It is important to differentiate two subpopulations of people who have tinnitus. For only a small proportion of people with tinnitus is it bothersome and affects their lives, evoking anxiety, annoyance, panic, problems with concentration, sleep, and so forth. Consequently, it is labeled clinically significant tinnitus as these people need professional help. The effects of tinnitus may reach a profound level, to the point of totally controlling patients’ lives and contributing to suicidal tendencies. On the other hand, the majority of
Tinnitus can be perceived as a wide variety of sounds. The most typical descriptions are ringing, hissing, cycads, escaping steam, and roaring. Tinnitus can be intermittent or continuous and may fluctuate in volume or change pitch. It can be perceived in one ear, in both ears, or in the head. The perceived loudness may vary significantly over a period of days. Examples of tinnitus and somatosounds are presented here. The sounds of tinnitus have been recreated by Dr. Jonathan Hazell, who used a musical synthetizer and interacted with patients until patients stated that the synthesized sound is very close to their tinnitus. In addition, a somatosound recorded in the ear canal of a patient and probably caused by jugular venous flow in the middle ear cavity is included, along with a somatosound from a patient diagnosed with palatal myoclonus.
Epidemiology Continuous tinnitus is perceived by 10–20% of the general population, with bothersome tinnitus affecting 3–8%. It is estimated that highly debilitating tinnitus exists in about 0.5% of the general population. Tinnitus occurs in all age groups. Recent data show that prevalence of tinnitus in children is similar to that observed in adults and that when children are bothered by tinnitus, it affects them to the same extent as it does adults. The prevalence of tinnitus perception increases significantly with aging; however, prevalence of the bothersome tinnitus declines for people 65 and older. As prevalence of hearing loss increases systematically with aging and prevalence of bothersome tinnitus decreases for older age groups, this observation argues against a simplistic link between bothersome tinnitus and hearing loss.
Medical Conditions Related to Tinnitus and Somatosounds Traumatic noise exposure, hearing loss, and head trauma are typically associated with tinnitus. The majority of cases of vestibular schwannoma exhibit tinnitus, and for Me´nie`re’s disease, low-pitch roaring, (tinnitus) is an obligatory symptom for diagnosis.
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Tinnitus accompany hyperacusis (defined as abnormally strong reactions to sound occurring within the auditory pathways) is present in more than 85% of cases, and hyperacusis is present in 25–30% of tinnitus cases. It appears that hormonal changes such as those that occur during pregnancy, menopause, or thyroid dysfunction promote tinnitus. Permanent damage of the inner ear typically produces permanent tinnitus, while transient impairment of inner ear function (e.g., resulting from moderate noise overexposure) may yield temporary tinnitus (called ‘disco tinnitus’). A long list of medications presumably inducing tinnitus is widely propagated; however, a critical review of the literature reveals that only aminoglycosides and quinine in high doses, some anticancer drugs, and withdrawal from benzodiazepines evoke tinnitus. Tinnitus could be a first indication of ototoxicity and emerges before hearing loss when patients are treated with ototoxic drugs. Salicylates (e.g., aspirin) reliably induce tinnitus in humans, and salicylates are used in animal models to produce tinnitus. As very high doses are needed to induce tinnitus, aspirin is not a significant factor clinically. Contrary to common belief, there are no clear data proving that any dietary manipulation evokes or relieves tinnitus. Smoking has been associated with increased prevalence of tinnitus, and alcohol in moderation offers some protective effect. Disorders of the somatosensory system (e.g., temporomandibular joint disorder) have been linked with tinnitus. Indeed, many patients can modulate their tinnitus by performing manipulations of the head and neck areas. Moreover, it is possible to evoke short temporal tinnitus by such manipulations in a significant proportion of people without tinnitus. Recent systematic neurophysiological studies have revealed strong somatosensory input to low levels of the auditory pathways such as the ventral and dorsal cochlear nuclei. It is possible to envision chronic tinnitus resulting predominantly from somatosensory input, but the data supporting such a possibility are limited. Currently, somatosensory modulation is used for research purposes (e.g., in imaging studies) as it offers a possibility of time-locked modulation of tinnitus. Somatosounds have a variety of sources. Frequently they are related to the cardiovascular system, typically abnormalities of blood flow in the head area that are pulsatile in synchrony with the heartbeat. Nonpulsatile somatosounds could be related to palatal or middle ear myoclonus or a constantly open eustachian tube, resulting in the perception of air flow over its opening. Another interesting case is the rare perception of spontaneous otoacoustic emissions generated in the inner ear.
Measurements Separate methods are needed for evaluation of tinnitus severity and for delineation of its perception. For tinnitus severity, a variety of questionnaires are used. Psychoacoustic properties of tinnitus are described by pitch match, loudness match, maskability (i.e., minimal level of white noise required to suppress its perception), and postmasking effects (disappearance of tinnitus for a certain time or increase in its loudness). Perceived pitch covers the full range of hearing, and in the majority of cases, tinnitus is perceived in the higher frequency ranges (above 4 kHz). The loudness match determined by psychoacoustic methods is stable for a given patient, disregarding subjective loudness perception. For the majority of patients, tinnitus loudness match is within 15 dB of their hearing threshold for the frequency corresponding to tinnitus pitch. Notably, there is no relation between psychoacoustic characterization of tinnitus and its severity. A number of physiologic measurements have been tried for objective detection of tinnitus. Evaluation of the specifics of cochlear sound transduction, function of the olivocochlear efferent system, spontaneous activity of the auditory nerve, auditory brain stem responses, and late cortical potentials have failed to provide clear correlates with the presence of tinnitus. Substantial progress has been achieved, however, with positron emission tomography, functional magnetic resonance imaging, voxel-based morphometry, and magnetoencephalography. Strongest results were obtained with magnetoencephalography, which demonstrated changes in tonotopic organization of the auditory cortex in frequency areas corresponding to tinnitus pitch match. Furthermore, the extent of tonotopic map modification correlates with subjectively perceived strength of tinnitus. Results of imaging studies regarding activation of various parts of the auditory system have frequently been inconsistent with one other. The majority of these studies, however, have shown significant activation of nonauditory structures, particularly the limbic system. Specifically, the auditory thalamus, various parts of the limbic system, the nucleus accumbens, the reticular formation, and the cerebellum have been shown to have changed activity in relation to tinnitus.
Differentiation between Experiencing Tinnitus and Being Bothered by Tinnitus As tinnitus is a perception of a sound, the auditory system has to be involved. At the same time, there is a lack of correlation between psychoacoustic characterization of tinnitus and its severity or treatment outcome. These observations suggest a need to identify
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two different classes of mechanisms: The first is those mechanisms related to generation to tinnitus-related neuronal activity (referred to, for brevity, in this article as the tinnitus signal) and tinnitus perception, which would be common to all people perceiving tinnitus regardless of whether they have a problem with it. The second class of mechanisms, specific to bothersome tinnitus, addresses the issue of how the tinnitus signal evokes negative reactions in the brain and body, resulting in tinnitus’ being a problem. Potential Generators of Tinnitus-Related Neuronal Activity
There is a consensus that in the majority of cases, the peripheral auditory system is involved in tinnitus generation. There is a small percentage of purely central tinnitus, such as occurs after cutting of the auditory nerve or in cases of auditory imagery or musical hallucinations. On the other hand, there is no consensus regarding other aspects of tinnitusrelated neuronal activity. A dominant view is that tinnitus perception results from detection of an increase of the spontaneous activity within the auditory pathways. There are data, however, strongly pointing out that actually modification in temporal patterns of discharges, specifically bursting activity, is related to tinnitus and that the increase of spontaneous activity is rather linked to hearing loss, which typically accompanies tinnitus. The synchronization of the activity between neurons has been proposed as well, and although absent at the lower level of the auditory system, it might play some role in the auditory cortex. The list of main proposed mechanisms of generation of tinnitus-related neuronal activity covers a wide variety of structures and dysfunctions, including hypoxia and ischemia in the cochlea; abnormal neurotransmitter release from the inner hair cells; abnormalities in transduction processes within the cochlea; damage of the auditory nerve; decreased activity of the cochlear efferent system; somatosensory–auditory interaction; neuronal plasticity, cortical reorganization of tonotopic maps, and hypersynchrony of neuronal discharges; enhanced sensitivity of the auditory pathways after decrease of the auditory input; and discordant damage or dysfunction of outer and inner hair cells. It is expected that for various types of tinnitus, different mechanisms are responsible for tinnitus emergence. Until now none has been proven. While other postulates might be correct, there is growing evidence supporting the last two hypotheses. Until the late 1980s there was no accepted animal model of tinnitus, and it was difficult to validate proposed hypotheses because of inherent limitations
of research on humans. A number of animal models are available now, allowing study of the physiological aspects of tinnitus perception. Enhanced Sensitivity of the Auditory Pathways and Emergence of Tinnitus after Decreased Auditory Input
It is possible to induce temporary tinnitus in a majority of people just by placing them in a very quiet environment. Moreover, tinnitus gets louder under such conditions. One of the mechanisms potentially involved in both these observations is enhanced sensitivity and increased amplification within the auditory pathways after decreased auditory input. Behavioral data argue that the auditory system (as other sensory systems) works as an automatic gain control system, that is, when input signal is low, then amplification increases, and when input signal is higher, then gain of the system is lowered. In an anechoic chamber, participants hear weak, normally unnoticeable sound, such as heartbeat or the movement of clothes caused by breathing, with all these sounds perceived as being quite loud. Recordings of single-unit activity from various centers of the auditory pathways have shown that the sensitivity of the neurons does indeed increase under conditions of low auditory input or when the inner ear is damaged. Opposite behavioral effects are observed when participants are in noisy environments. Enhanced amplification within the auditory pathways may happen as a result of various reasons and evoke or enhance tinnitus or induce hyperacusis. Models of Tinnitus
A challenge to modeling tinnitus is the lack of abundant neurophysiological data and the fact that there are likely to be several types of tinnitus, each generated by a different underlying mechanism. A starting point for models is the apparent paradox of a lack of tinnitus-related activity in the cochlea coupled with the presence of sound perception, pointing to a central origin for the generation of tinnitus. The observation that tinnitus often accompanies hearing loss focuses attention on the central auditory pathway. One simple model would propose that a normal balance of excitatory and inhibitory input to some center in the pathway is disrupted by hearing loss. If the disruption is to the inhibitory input, the resulting excitatory input is unbalanced and could lead to tinnitus. This discordant dysfunction theory has been applied to the dorsal cochlear nucleus, a cochlear nucleus subdivision that has abundant interneurons, many of which are inhibitory. Indeed, experimental evidence in animals shows abnormally high ‘spontaneous’ activity in this center accompanying hearing loss. The particular neural pathways involved remain obscure. The auditory nerve
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does provide two types of input to the dorsal cochlear nucleus: type I fiber inputs from the inner hair cells and type II fiber inputs from the outer hair cells. Inner hair cells are contacted by 95% of afferent fibers of the auditory nerve (which are type I, thick, fast, and myelinated), and these cells act as a transducer, converting the vibration of the basilar membrane of the cochlea into electrical impulses within the auditory nerve. Total deafness occurs if all these cells are damaged, even with untouched outer hair cells. Outer hair cells function as a mechanical amplifier, enhancing vibration for the lower half of the range of perceived sound levels by about 60 dB. It is possible to have normal hearing even if 30% of outer hair cells are damaged. Rapid decrease of their function has been associated with an emergence of tinnitus in humans. They are contacted by about 5% of auditory nerve fibers (type II, thin, slow, and unmyelinated). Outer hair cells are preferentially damaged by intense sound exposure. However, both type I and type II inputs are likely to excite their targets in the brain, and thus further inhibitory interneurons, perhaps to one of these pathways within the dorsal cochlear nucleus, would need to be involved to generate unbalanced excitation. Specifically, the discordant dysfunction theory proposes that when an imbalance of functional properties of outer and inner hair cells occurs, it yields the disinhibition of spontaneous neuronal activity in the dorsal cochlear nucleus, causing a general increase of the spontaneous activity and emergence of bursting, epileptic-like activity, which after further processing within the auditory pathways is perceived as tinnitus. Therefore, while there is no vibratory activity related to tinnitus in the cochlea, the cochlea still may serve as a source of the tinnitus neuronal signal. The Neurophysiological Model of Tinnitus
Disregarding specifics of mechanisms yielding the presence of the tinnitus signal in the auditory pathways, there is consensus that once it is detected, it is perceived as a sound. Little attention has been given to mechanisms involved in converting tinnitus from benign perception of a sound to a significant problem affecting people’s lives. In the past, the dominant approach was through psychology, with no attempt to identify specific neurophysiological structures and mechanisms involved. The neurophysiological model of tinnitus, which attempts to approach tinnitus from the point of view of neuroscience, points out the inherent involvement of the central nervous system (CNS) in tinnitus, and attempts to indicate systems, structures, and the role of specific mechanisms of the brain function in clinically significant tinnitus.
The observation that tinnitus pitch, maskability, and loudness are not correlated at all with tinnitus severity for the population of patients strongly supports the postulate that the auditory system is secondary in clinically significant tinnitus. The neurophysiological model of tinnitus postulates that in the case of bothersome tinnitus, systems other than the auditory system of the brain have to be involved. The limbic and autonomic nervous systems play the major role, and other systems, such as prefrontal cortex and cerebellum, may be involved as well. Furthermore, the model stresses strongly the importance of subconscious processing of the information and the importance of the principles of conditioned reflexes in governing the connections between auditory and other brain systems. Briefly, tinnitus-related neuronal activity which originates in the auditory system starts to activate other brain systems because of both cognitive assessment of tinnitus and subconscious connections created as the result of one of the principles of conditioning. Temporal association of signal (tinnitus) and reinforcement (annoyance, strong emotional upheaval due to any reason) are sufficient to produce this conditioned reflex. Indeed, a study performed to identify factors most frequently linked to the emergence of clinically significant tinnitus revealed that in a majority of cases, it develops as the result of factors totally irrelevant to hearing, such as retirement, losing a job, divorce, and so forth. The diagram of the main systems and connections involved in clinically significant tinnitus is presented in Figure 1(a). In cases when people experience tinnitus but are not bothered by it, only the auditory system is activated. Once tinnitus-related neuronal activity spreads to the limbic and the sympathetic part of the autonomic nervous systems, the new functional connections are created, enhanced, and governed to a large extent by the principles of conditioned reflexes. The autonomic nervous system consists of two reciprocally antagonistic parts, the sympathetic and the parasympathetic systems. Activation of the sympathetic system prepares people for physical or mental action, and activation of the parasympathetic system sets the stage for rest and relaxation. Overactivation of the sympathetic system yields stress, anxiety, panic attacks, and the fight-or-flight reaction. All behavioral reactions exhibited by tinnitus patients, such as anxiety, annoyance, panic, decreased ability to enjoy life activities, problems with attention, and problems with sleep, are consistent with activation of the sympathetic system. When the term ‘autonomic nervous system’ is used in this discussion, it denotes the sympathetic system unless otherwise specified. According to the neurophysiological model of tinnitus, problems
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Auditory and other cortical areas Perception and evaluation (consciousness, memory, attention)
Auditory subconscious Detection/processing
Limbic system Emotions
Auditory periphery Source
Reactions
Autonomic nervous system
a Auditory and other cortical areas Perception and evaluation (consciousness, memory, attention)
HP Auditory subconscious Detection/processing
Limbic system Emotions
HER
Reactions
HAR
Auditory periphery Source
Autonomic nervous system
b Figure 1 The neurophysiological model of tinnitus. (a) The block diagram outlining structures and connections involved in clinically significant tinnitus. The tinnitus signal, typically generated at the periphery of the auditory system, is detected and processed in subconscious pathways of the auditory system and finally perceived at the auditory cortex. If tinnitus is classified as an important negative stimulus, self-enhancing loops, governed by principles of conditioned reflexes, develop. Note existence of two loops: high, involving consciousness, and low, the subconscious loop. (b) Specific functional connections at which habituation of tinnitus occurs. HER, habituation of emotional reactions; HAR, habituation of reactions evoked by the autonomic nervous system; HP, habituation of tinnitus perception. The primary goal of tinnitus retraining therapy is to achieve habituation of reactions; habituation of perception will follow automatically.
arise from proper reaction of the brain to an inappropriate stimulus, that is, the reactions would be appropriate to a life-threatening stimulation, but tinnitus perception results from compensatory action of the auditory system to a situation which does not indicate danger. The activation of the limbic and autonomic nervous systems by tinnitus signal occurs via two pathways: conscious and subconscious, or high and low loops, respectively (Figure 1(a)). The conscious loop involves high cortical areas, perception, cognition, and verbalization. During the process of development of clinically significant tinnitus, this path is created first.
Tinnitus attracts attention, thoughts, concerns, and fears, which activate the limbic and autonomic nervous systems. If these initial thoughts are properly addressed by demystification of tinnitus and its categorization as a neutral stimulus, initial activation of the limbic and autonomic nervous systems is extinguished, and tinnitus does not become a problem. If, however, these thoughts are not addressed properly or, even worse, are enhanced by negative counseling, these connections become stronger, and problems caused by tinnitus are enhanced. The presence of reciprocal connections – signals from the auditory subcortical and cortical areas activating the limbic system and evoking
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(negative) emotions – in turn changes reactivity of the auditory centers, causes enhancement of initial connections, and finally results in establishment of strong reactions of the limbic and autonomic nervous systems. These reactions act as negative reinforcement for a conditioned reflexes arc which links the tinnitusrelated neuronal activity within the auditory system (conditioned stimulus) with reactions. They enhance cognitive concerns as well as further worsening the problem. Note that the outlined processes by definition involve neuronal plasticity. At a subconscious level, the tinnitus signal is going through strong functional connections between the medial geniculate body and the lateral nucleus of the amygdala, which is one of the crucial components of the limbic system. This low loop develops after the high loop, it is governed by principles of conditioned reflexes, and it might become dominant in chronic tinnitus. Therefore, because of the presence of the low loop, the activation of the limbic and autonomic nervous systems might occur even without conscious perception of tinnitus. Notably, a signal conveyed via this route cannot be directly modified by conscious thinking, and a method appropriate for retraining of conditioned reflexes would be more appropriate.
Treatments Treatment of tinnitus is a challenging problem at both the theoretical and the clinical level. Observations of what works and what does not provide some insight into mechanisms of tinnitus. Thousands of years of attempts at treatment (tinnitus was first described in Babylonian clay tablets) have not brought consistently positive results. Only selected treatment methods are outlined. Suppression or Weakening the Tinnitus Signal
The first class of approaches is aimed at suppressing tinnitus perception temporarily (masking) or partially decreasing it. In neurophysiological terms, total suppression of tinnitus perception would mean that detection of tinnitus-related neuronal activity is prevented by providing the auditory system with another stimulation which would make detection of the tinnitus signal impossible. Attempts to apply this method have revealed that clinically relevant suppression of tinnitus perception in practice can be achieved in only a small percentage of cases. Direct stimulation of the auditory nerve via a cochlear implant increases the effectiveness by about 50%, but this method can be used only by the very small proportion of tinnitus patient who are profoundly deaf. Electrical
stimulation applied outside the cochlea has failed to be substantially effective. Direct electrical stimulation of the auditory cortex is under investigation but has failed so far to show superior results. A weakening of tinnitus-related neuronal activity can be achieved via a variety of methods. The simplest, and the most popular, is by enriching auditory background stimulation, and it is implemented in a wide variety of sound therapy. Two neurophysiological mechanisms are bases for decreasing the strength of the tinnitus signal (i.e., tinnitus-related neuronal activity). First, the strength of any signal depends on its difference with background rather than on its absolute physical value. Second, the sensitivity to sensory signals depends on longer-term average input. Consequently, by an increase of the auditory background, the tinnitus signal is decreased due to the combined action of both mechanisms. The type of sound is in this respect secondary; however, it plays a role because of other factors (e.g., ease of habituation, inherent preference for certain sound levels, emotional and cognitive connotations). Another class of treatments attempts to modify the tinnitus signal at the central level rather than by stimulation of the periphery. In addition to direct electrical stimulation of the auditory cortex, transcranial magnetic stimulation has been tried recently. Strong pulses of the magnetic field are applied to the skull outside the cortical area to be stimulated. Magnetic field crosses the skull easily and evokes a strong electrical field in the cortex, which in turn stimulates cortical fibers. The effects on the brain function depend on the frequency of stimulation. High frequency evokes direct inhibitory action on the cortical activity, while low-frequency stimulation appears to induce plastic changes in organization of cortical networks and potentially their interaction with subcortical centers. While it is not clear what specific reorganizations occur, this approach has been shown to attenuate tinnitus. The effects are mild, however, and it is not clear whether they are long lasting. Nevertheless, observation that transcranial magnetic stimulation has some impact on tinnitus supports the importance of the modification of the CNS in tinnitus treatment. Psychological Approaches
Psychological treatments cover a variety of approaches, from simple attempts to distract attention from tinnitus to improved coping and up to behavioral cognitive therapy. Behavioral cognitive therapy seems to be most effective in the class of psychological treatment and is based on the assumption that because thoughts evoke emotions, it is possible by changing thoughts to
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modify emotions evoked by tinnitus. There are wellestablished, effective methods to achieve this goal, and this method is effective in a significant proportion of patients. According to the neurophysiological model of tinnitus, behavioral cognitive therapy nullifies the high loop and therefore decreases stimulation of the limbic and autonomic nervous systems. Medications
Pharmacological approaches have been tried for a long time and, in spite of their lack of success, are still among the most popular. Some medications aim at the periphery of the auditory system, others at the limbic and autonomic nervous systems to decrease anxiety and annoyance and improve coping. Trials of new pharmacological candidates are ongoing, but so far research has failed to show any drug to be consistently effective for tinnitus. Tinnitus Retraining Therapy
All treatment methods presented so far aim at modification of tinnitus perception or signal or alleviation of tinnitus-evoked reactions. Tinnitus retraining therapy (TRT) differs in this respect as it aims to retrain the brain to extinguish specific, tinnitus-related functional connections between the auditory and the limbic and autonomic nervous systems and through this mechanism to decrease or remove tinnitus-evoked reactions (Figure 1(b)). TRT attempts to modify neither the source of the tinnitus signal nor the brain centers involved in reacting to it. As a consequence, TRT is independent of the source of the tinnitus signal (tinnitus etiology) and can be used to treat any type of tinnitus. Briefly, TRT consists of counseling and sound therapy, both strictly based on the neurophysiological model of tinnitus. The goal is to achieve habituation of the tinnitus-evoked reactions, which will be followed automatically by habituation of tinnitus perception (Figure 1(b)). Habituation of reactions is basically identical to the passive extinction of conditioned reactions. TRT uses a modified version of passive extinction of conditioned reflexes in which both the reactions and the stimulus are decreased simultaneously. Habituation of tinnitus can be achieved by a variety of methods. TRT’s approach is easily implemented and works on both the tinnitus and the decreased sound tolerance (hyperacusis and misophonia) that frequently coexists with tinnitus. The role of counseling is to reclassify the tinnitus signal into the category of neutral stimuli, as habituation of any stimulus is difficult when the stimulus has negative connotations and impossible when these associations are very strong. It effectively disrupts the higher loop and decreases stimulation of the limbic
and autonomic nervous systems by cognitive processes. In this respect it is similar to behavioral cognitive therapy but uses a different counseling approach. Sound therapy is the second part of TRT. It aims to decrease the strength of the tinnitus signal through application of a number of guides provided by the neurophysiological model of tinnitus (e.g., use of sound during the night and avoiding annoyance and suppression of tinnitus perception).
Future Goals It has been argued that tinnitus is a phantom auditory perception and should be analyzed from the point of view of neuroscience rather than by ear-oriented (e.g., otolaryngological or audiological) or mind-oriented (e.g., psychological) approaches. Significant progress in understanding mechanisms of tinnitus and its treatment has been achieved in large part because of the shift from earcentric or black-box approaches to neuroscience. A number of important neurophysiological questions remain, however. Significant efforts focus on delineating structures in the brain which are involved in the phenomenon of tinnitus. Imaging studies are consistent in indicating involvement of the limbic system and parts of the brain involved in anxiety, but data from the auditory system are much more variable and unclear. Researchers still debate what tinnitus-related neuronal activity looks like. The dominant belief, that it takes the form of increased spontaneous activity, has been challenged, and it has been proposed that changes in temporal patterns of neuronal dischargers, involving high-frequency, bursting, epileptic-type activity, is in reality a neuronal correlate of tinnitus. There is even less clarity on the neurotransmitters and receptors involved. Gamma-aminobutyric acid, glutamate, serotonin, and other systems, as well as N-methyl-D-aspartate receptors, have been implicated. There are, however, no data proving clear involvement of any of these systems, and drug trials for tinnitus so far argue against a dominant involvement of any of these systems in tinnitus. Due to obvious limits on research on humans, animal models of tinnitus are extremely important. Since the mid-1980s, when the first valid animal model of tinnitus was introduced, a variety of models have emerged, including most recently a model based on prepulse inhibition of the startle reaction. By acknowledging the crucial involvement of the CNS in tinnitus and combining animal and human research, it should be possible to achieve better understanding of this elusive phenomenon and to find more effective methods for its alleviation.
1008 Tinnitus See also: Auditory System: Central Pathway Plasticity; Auditory System: Central Pathways; Auditory/ Somatosensory Interactions; Deafness; Hair Cells: Sensory Transduction.
Further Reading Chen G-D and Jastreboff PJ (1995) Salicylate-induced abnormal activity in the inferior colliculus of rats. Hearing Research 82: 158–178. Eggermont JJ and Roberts LE (2004) The neuroscience of tinnitus. Trends in Neurosciences 27: 676–682. Jastreboff PJ (1990) Phantom auditory perception (tinnitus): Mechanisms of generation and perception. Neuroscience Research 8: 221–254.
Jastreboff PJ, Brennan JF, Coleman JK, and Sasaki CT (1988) Phantom auditory sensation in rats: An animal model for tinnitus. Behavioral Neuroscience 102: 811–822. Jastreboff PJ and Hazell JWP (2004) Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. Cambridge: Cambridge University Press. Jastreboff PJ and Jastreboff MM (2006) Tinnitus retraining therapy: A different view on tinnitus. ORL: Journal for Oto-RhinoLaryngology and Its Related Specialties 68: 23–29. Jastreboff PJ and Jastreboff MM (in press) Tinnitus and hyperacusis. In: Ballenger JJ, Snow JB Jr., and Ashley WP (eds.) Ballenger’s Otorhinolaryngology Head and Neck Surgery, 17th edn., ch. 31. San Diego, CA: Singular Publishing. Snow JB (2004) Tinnitus: Theory and Management. London: BC Decker.