Tinnitus and Its Treatment

University of Texas at Dallas
School of Behavioral and Brain Sciences
Callier Center for Communication Disorders

INTRODUCTION:

Tinnitus is a diverse group of disorders, which can be divided into two main groups; 1- objective tinnitus, and 2- subjective tinnitus.

Objective tinnitus is caused by sound generated within the body. It can often be heard by an observer. Subjective tinnitus is much more common and is a source of far greater suffering, than is objective tinnitus. Subjective tinnitus can only be heard by the patient. There are no objective means available for detection of subjective tinnitus or for evaluating the intensity or character of subjective tinnitus.

OBJECTIVE TINNITUS:

Objective tinnitus is rare. It activates the ear's sensory organs and can often be diagnosed by its character, or by auscultation. Objective tinnitus can be caused by a number of etiologies. For example, objective tinnitus can be caused by turbulent blood flow, such as that which occurs when blood passes through a narrow constriction. Such tinnitus is usually pulsatile and often synchronous with the heart rate. Objective tinnitus can be caused by an open Eustachian tube that allows respiratory sounds to reach the middle ear. Tinnitus can be caused by muscle contractions such as that of the tensor tympani or the muscles in the pharynx. Tensor tympani contractions can be specifically diagnosed by recording the ear's acoustic impedance. The treatment of objective tinnitus varies, based on the specific etiology that causes the tinnitus.

In this article, we will concentrate on subjective tinnitus, its pathophysiology and treatment.

SUBJECTIVE TINNITUS:

There are many kinds of subjective tinnitus. One cannot expect to find a single treatment that is effective for all types of tinnitus. There are no known objective methods or tests that determine the strength, character or cause of subjective tinnitus. Only the individual who has the tinnitus can determine its strengths or character. The French surgeon Leriche said ''The only tolerable pain is someone else's pain.'' This statement is applicable to tinnitus. Tinnitus is indeed similar to some forms of pain, in particular, central neuropathic pain (see reference A, B). Tinnitus has been regarded as one type of phantom sensations (see reference C).

Like pain, the severity of tinnitus varies widely. It can be ''mild,'' not interfering noticeably with a person's daily life, it can be ''moderate,'' causing some annoyance and being unpleasant. However, tinnitus classified as ''severe'' affects a person's entire life style in significant ways and may be accompanied by abnormal perception of sounds such as hyperacusis, phonophobia (fear of sound) or both. Severe tinnitus may lead to depression or suicide.

The prevalence of severe tinnitus is unknown, but estimates are that 50 million people in the United States have some form of tinnitus. Research efforts specific to tinnitus lags behind research efforts on pain, based on the number of published papers. A recent Medline search from 1966-2003 produced 193,756 articles on pain, and 4,182 articles on tinnitus.

Subjective tinnitus can be caused by disorders that affect the ear, the auditory nerve, the central auditory nervous system and other parts of the nervous system. Abnormal neural activity in any part of the auditory nervous system may cause tinnitus. There is no known method to determine the anatomic location of the abnormality that causes tinnitus.

Similar to ''referred pain,'' considerable evidence supports the conclusion that most forms of severe subjective tinnitus originate in the central nervous system, despite the presence of the auditory symptom (tinnitus). Because the symptom is auditory and referred to the ear, clinicians and researchers search for the cause of tinnitus in the ear. However, the anatomic location of the abnormality in most patients with severe tinnitus is the nervous system.

Tinnitus that originates in the nervous system may be caused by insult or injury to the auditory nerve. For example, if a tumor or blood vessel is in close contact with the root of the auditory nerve, the physical contact with the auditory nerve may initiate neural activity resulting in hearing loss, tinnitus or other auditory phenomena. Physical injury to the auditory nerve, such as may be caused by surgical interventions (iatrogenic injuries), may cause activity in the auditory nerve that is interpreted as a sound when it reaches central parts of the nervous system. It has been suggested that slight injury to the auditory nerve may cause neurons to fire in a way similar to their normal response to sound, and thereby cause the sensation of sounds (see reference D).

Changes in the function of central structures of the auditory nervous system can also cause tinnitus. Such changes are often caused by plastic changes in the auditory nervous system. Plastic changes can occur because the nervous system is not ''hard wired'' and therefore its function can change over time. Many factors can cause expression of neural plasticity. One powerful factor is deprivation of sensory input. Reorganization of the nervous system is a frequent cause of symptoms and signs of other diseases (see reference E) and frequently presents in the form of neuropathic pain (see reference F). However, neural plasticity is also involved in abnormal motor function and may be responsible for spasm or spasticity.

Tinnitus often occurs in tandem with hearing loss, especially high frequency hearing loss. Plastic changes within the nervous system associated with tinnitus may be caused by the auditory nervous system as it compensates for hearing loss by increasing its' sensitivity to the nervous system. If the increase in sensitivity is too large (overcompensation) it may cause neural activity similar to that normally caused by sound, and that neural activity may manifest as a sensation of sound - tinnitus. Hyperactivity, hypersensitivity, and other changes that often accompany tinnitus may be caused by the same plastic changes in the function of the auditory nervous system.

The concept of deprivation of input initiating neural plasticity has been confirmed in animal experiments. These experiments have shown that deprivation of input to the auditory nervous system causes abnormal function of neurons in the cochlear nucleus and the inferior colliculus (see reference G).

Exposure to loud sound is often followed by tinnitus. Animal experiments have shown that overstimulation (i.e., exposure to loud sounds) can cause plastic changes in the auditory nervous system (see reference H). It is possible that abnormal activity in an injured auditory nerve may cause the expression of neural plasticity. The fact that tinnitus may be caused by plastic changes in the nervous system is yet another similarity with pain, specifically with central neuropathic pain (see reference A).

Expression of neural plasticity may shift the balance between inhibition and excitation (see below) and create a hyperactive state of nuclei in the auditory nervous system or, it may cause re-routing of information to other parts of the nervous system that are not normally activated by sounds.

Balance between inhibition and excitation:

Proper balance between inhibition and excitation is important for normal functioning of the central nervous system. Shifting the balance between inhibition and excitation may cause a multitude of symptoms, depending on which CNS system is affected by the shift in balance.

Tinnitus, hyperacusis and hypersensitivity to sounds may in fact, be caused by a shift in balance between inhibition and excitation in the nuclei of the auditory pathways. Many treatment protocols are directed at restoring the function of the nervous system to its normal state. Hyperactivity (such as that suspected to be the cause of tinnitus) can be caused by either increased excitation or decreased inhibition. In the auditory system (as in many other CNS systems), inhibition is mostly mediated by GABA (gamma amino butyric acid). There are two main groups of receptors that respond to that transmitter substance, the GABAA and the GABAB receptors. Several different (excitatory) transmitter substances cause
excitation.

Re-routing of information:

Some patients with tinnitus experience cross-modal sensory interactions, which has been demonstrated by stimulating the somatosensory system. Such stimulation has been shown to alter the perception of the tinnitus in some patients (see references I, J and K).

Cross-modal interaction has been demonstrated in studies of patients with tinnitus. Sound was presented through headphones, and the perception of loudness varied when the median nerve along the wrist was stimulated using weak electrical impulses (see reference K). Cross-modal interaction between the auditory and the somatosensory system occurs normally in young children and decreases with age and it is rare in individuals above the age of 20 years without tinnitus (see references K and L). Other studies have demonstrated interaction between the perception of tinnitus and activation of the somatosensory system (see references I, J and K). Cross-modal interaction that occurs in adults with tinnitus must, therefore, be regarded as an abnormality related to their tinnitus. Interaction between the somatosensory and auditory systems may also explain why individuals with Temporo-Mandibular Joint (TMJ) problems sometimes also have tinnitus (see reference M) and may also address the association between neck muscle tension and tinnitus and gaze related tinnitus (see reference N). The efficacy of electrical stimulation in treatment of some forms of tinnitus may also be related to cross modal between the auditory and the somatosensory systems (see reference O).

The physiologic and anatomic basis for cross-modal interaction is probably related to involvement of non-classical auditory pathways. The non-classical auditory pathway (also known as the extralemniscal pathway) is an ascending auditory pathway that conducts auditory information to the brain in a different way than the classical auditory pathway. The non-classical pathway is much less well known than is the classical pathway. In fact, most textbooks only describe the classical auditory pathway. One main difference between these two auditory pathways is that neurons in the classical pathway only respond to sound, while neurons in the non-classical pathway respond to sound and other sensory modalities, such as touch and light. Neurophysiologic studies in animals have shown that the response of some neurons within the non-classical pathway to sound can be modulated by stimulation of the somatosensory system.

Since only neurons in the non-classical auditory pathways respond to other modalities, the presence of such ''cross-modal'' interaction has been interpreted as an indication that non-classical auditory pathways are functional in children and some individuals with tinnitus. The observation that some patients get relief from tinnitus by electrical stimulation of the skin is another sign of cross-modal interaction (see reference O) and thus activation of the non-classical auditory pathway. Some patients may perceive sounds from stimulation of the skin, such as rubbing their back with a towel, and that too, indicates non-classical pathways are active.

There are several anatomical differences between the classical and the non-classical auditory pathways (see references B and P). Thus, while the classical pathways use the ventral thalamus, the non-classical pathways use the dorsal thalamus (see Figure 1). Neurons in the ventral thalamus project to neurons in the primary auditory cortex whereas the neurons in the dorsal portion of the thalamus project to secondary and association cortices, thus bypassing the primary auditory cortex. Neurons in the dorsal thalamus make direct connections to neurons in the limbic system, most notably the amygdala. Auditory information can also reach the nuclei of the amygdala through the classical pathways, but only through a long pathway involving the primary, secondary auditory cortices and association cortices (see Figure 1). This is known as the ''high route'' to the amygdala and the pathway to the amygdala from the dorsal thalamus is known as the ''low route'' to the amygdala (see Figure 2).

Normally auditory and other sensory information reach the nuclei of the amygdala through the ''high route'', which include the auditory cortex, secondary auditory cortices and association cortices (see references P and Q, see Figure 1).


Fig 1.

A. Schematic drawing of the classical ascending auditory pathway from one ear, using the ventral part of the thalamus and projecting to the primary auditory cortex.

B: Non-classical ascending pathway from one ear showing input from other sensory systems. This pathway uses the dorsal thalamic nucleus and projects to secondary and association cortices, making subcortical connections to limbic structures (amygdala) (From Moller, 200316).


Fig 2. Connections from the auditory system to the amygdala, through the high route and the low route. AL: lateral nucleus of the amygdala, ABL: basal nucleus of the amygdala, ACL: central nucleus of the amygdala (From Moller, 2003 16).

The fact that non-classical auditory pathways may be abnormally open in some patients with tinnitus would allow conduction of auditory information to the amygdala through the subcortical route (''low route'') and that may explain the affective symptoms that often accompany severe tinnitus, such as depression and phonophobia.

It is not precisely known how non-classical pathways become involved in conduction of auditory information in some patients with tinnitus, but there are indications that expression of neural plasticity is involved. The non-classical auditory pathways could be activated through the expression of neural plasticity through which ''dormant'' synapses could be ''unmasked'' and thereby open connections that are normally blocked by non-conducting (masked) synapses. Expression of neural plasticity may thus cause redirection of auditory information. Re-direction of auditory information to the non-classical auditory pathway (see references A, B and K) may cause abnormal activation of the neurons in the nuclei of the amygdala and that may explain why some patients with tinnitus experience symptoms of affective disorders such as phonophobia and depression.

Treatment of tinnitus:

Perhaps changes in function of the nervous system initiated by plastic changes can be reversed with appropriate intervention. For example, the effect of sound deprivation may be reversed by appropriate exposure to sound, reversing the expression of neural plasticity.

Some medical treatments for tinnitus attempt to restore the balance between inhibition and excitation by increasing excitation or by decreasing inhibition. Since GABA (gamma amino butyric acid) is the most common inhibitory transmitter substance in the brain, treatments have been directed to enhance the function of GABA receptors. Other treatments have been aimed at lowering excitation. Typical medications that strengthen inhibition belong to the benzodiazepine group such as Xanax (Alprazolam), Klonopin (Clonazepam) and Valium (Diazepam). These medications act by strengthening the GABAA receptors. The GABAB receptor and Baclofen (baclofen is used for treating muscle spasms and some forms of pain) can make that receptor more effective

Drugs that decrease excitation, and that have been used in treatment of tinnitus, include drugs used to treat some forms of epilepsy. One drug that was assumed to work as a sodium channel blocker was a local anesthetic, Lidocaine. That drug was previously used to stop epileptic seizures, but other drugs have replaced Lidocaine for that purpose. Other drugs with presumed similar action have been used in pursuit of medical treatments for tinnitus; Tegretol (Carbamazepine), Dilantin (phenytoin), Tocainide, and Mexiletine (see reference R) are examples of such drugs. However, all of these drugs have serious side effects, short action duration, or the need to be administered intravenously.

Animal experiments have demonstrated that GABA receptor agonists can restore inhibition in the inferior colliculus (see reference S). In such studies, noise exposure has been used to create hyperactivity in the auditory system. Noise exposure alters temporal integration in the auditory nervous system and those changes have been accepted as signs of hypersensitivity, similar to that which causes tinnitus. Animal experiments have shown that benzodiazepines and baclofen can restore temporal integration to normal values in the inferior colliculus in animals exposed to loud noise.

CONCLUSIONS:

There are indications that cross-modal interaction is a sign of involvement of the non-classical auditory pathways and is caused by the expression of neural plasticity. The fact that similar cross-modal interaction occurs in young children indicates that the neural circuitry of the non-classical auditory pathway is anatomically intact in adults -- but not activated in normal individuals.

If the above conclusion is true, it should be possible to restore normalcy by blocking these synapses. That could be done by appropriate sound exposure and perhaps through descending input from higher brain centers, such as could occur through hypnosis.

The efficacy of Tinnitus Retraining Therapy (see reference T) may rely on promoting expression of neural plasticity that restores normalcy regarding the conduction of sound information to higher brain centers.

Electrical stimulation of the skin is not in common use but earlier studies showed efficacy in certain individuals with tinnitus (see reference O). More recently, it has been shown that stimulation of the cerebral cortex, through induction of electrical current by applying impulses of a strong magnetic field to the head, or through implanted electrodes (i.e., deep brain stimulation) has been shown to be effective in reducing tinnitus in a few patients (U). The general efficacy of such stimulation is not yet known because it has only been tried with a few individuals (U).

It is not known how electrical stimulation of the auditory cortex works, it may, in fact, act on the thalamic auditory nucleus (MGB) through the abundant descending pathway from the auditory cortex. However, despite many attempts, treatment of tinnitus is still unsatisfactory in many patients. Since tinnitus is essentially a group of different disorders, which presumably have multiple etiologies and are likely treatable with different protocols. Much more research is needed to develop effective treatments for severe tinnitus.


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