Tinnitus is what people experience when they hear a sound that has no external source. Roughly 10 to 20 percent of the U.S. population hears what is described as a ringing, buzzing, or humming. Its benign "acute" form lasts only a few seconds, a few minutes, or rarely a few days or weeks. In its chronic form--which between 0.5 and 1 percent of Americans experience--it lasts months or years. It often worsens during periods of stress, becoming most noticeable in quiet settings such as when trying to fall asleep. Chronic sufferers can feel depression, anxiety, and even thoughts of suicide.
Tinnitus can result from excessive noise exposure, head injury, and ear infection. It also frequently occurs with aging. To treat the condition, doctors often recommend "masking," using a sound-producing instrument to cover up the tinnitus. Hearing aids can also mask, since the amplification of external sounds can decrease the effect of tinnitus. Drug therapy or psychotherapy to treat depression and anxiety reduces the emotional effects. Counseling, education, and sound therapy are combined in Tinnitus Retraining Therapy.
THE ORIGINS OF TINNITUS
Although most patients can benefit from the treatments noted above, they do not address the actual origins of tinnitus. The traditional view that tinnitus-producing signals are generated by the ear has been called into question. Many profoundly deaf patients who lack cochlear or inner ear function have tinnitus. Also, even after the auditory nerve has been surgically sectioned, tinnitus often remains--sometimes worse than before. Patients with no tinnitus before surgery to remove tumors
of the auditory nerve have about a 40 percent chance of developing tinnitus.
A wide range of studies has shown that tinnitus comes from "plasticity" or changes in the brain triggered by injury to the ear. These findings have major clinical implications. Normally, neurons in the central auditory system (the portion of the auditory pathway that lies in the brain) are held in a state of balance between excitation and inhibition. When no sounds are present, their levels of activity are low. In the presence of sound, the level of excitation is increased in the central auditory system as the auditory nerve is activated. The brain interprets this activation as sound.
Cochlear damage caused by loud sound and other ear problems involves injury to auditory receptor cells called hair cells. When hair cells are damaged, the auditory nerve's ability to transmit messages that tell the brain when sounds are present is impaired. The central auditory system shifts its normal balance of excitation and inhibition toward the side of excitation. As a result, the neurons in this state of hyperactivation resemble those which are normally seen only when sound is present.
Two other types of neuron imbalance occur after injury to the ear: an increase in synchrony and an increase in bursting activity. Synchrony describes neurons firing at the same time. This means that when an impulse is generated by one neuron, other neurons in the cell population generate impulses at the same time. Stimulation with sound increases synchronous firing across neurons in the auditory system. There is evidence that injury to the ear by noise exposure or exposure to drugs that damage hair cells causes an increase in synchronous firing. Thus, researchers believe tinnitus may emerge as a consequence of increased synchrony.
Bursting activity in the central auditory system describes how neurons tend to generate impulses in clusters. Such clusters occur in some neurons even in the normal auditory system, but the incidence of bursting is greatly increased after injury to the ear. Animal studies have shown impulse bursts to be correlated with tinnitus. The level as well as the timing of bursting activation appear to be factors.
NEW AVENUES FOR TREATMENT
There has been increasing interest in chemical pathways that underlie abnormal patterns of activity leading to tinnitus. One type of mechanism that has been implicated in the induction of tinnitus is neural plasticity, the ability of the brain to adjust itself in an effort to compensate for reduced or weakened input.
Neurons can alter the strength of inhibition or excitation by regulating the amount of neurotransmitters that they release. Alternatively, receptors for those transmitters can be regulated. Or the strength of the neurons' connections can change: Inhibitory connections can be weakened while excitatory connections can be strengthened.
Over the past five years or so, a considerable amount of research has been done to determine which of the above types of plasticity occur in the central auditory system of animals with damaged inner ear hair cells or in aging animals. The studies show a reduced number of receptors for inhibitory neurotransmitters in the auditory pathway. The best example is the receptor for glycine. Other research points to increases in the number of receptors or in the number of connections that serve an excitatory role. Two excitatory transmitters are glutamate and acteylcholine. Receptors for both have been found to be overproduced following exposure to noise.
It is now widely expected that tinnitus relief might be achieved by restoring the normal balance of inhibition and excitation in the auditory system. Drugs that target receptors known to play a role in the induction of plasticity, such as NMDA receptors, are of particular interest. So far, a number of studies suggest that blocking NMDA receptors can eliminate tinnitus in animal studies. A few case reports also suggest that some NMDA receptor blockers can help people with tinnitus. Results from a number of placebo-controlled clinical trials examining the effects of these agents on a larger patient population should appear in the next few years.
Research suggests that the sounds of tinnitus can be reduced in loudness by restoring input from the areas of the auditory system that have lost their normal input.
Each center of the auditory system possesses a map of sound frequency. This means that for each sound frequency we hear, there are neurons dedicated to that frequency. Neurons tuned to different frequencies are laid out in an orderly way, producing a frequency map that is analogous to the way different frequencies are laid out on a piano keyboard. Damage to the inner ear deprives these maps of input from the damaged area of the inner ear. That lost input then triggers plasticity in the central auditory system that leads to a shift in the balance of excitation and inhibition. Animal studies have shown that if the region of the map with weakened input is stimulated with sound, the changes in the brain that underlie tinnitus do not develop. In more recent studies, patients with tinnitus have experienced improvements in the loudness of their tinnitus when the sound delivered to the ear concentrates energy in the frequency range that has been damaged.
Perhaps the most intriguing new discovery is that contracting certain muscles of the head and neck, such as jaw clenching or resisting pressure applied to the side of the head, can alter tinnitus. Up to 80 percent of tinnitus patients can change the loudness or pitch of their tinnitus in this way. Recent studies have confirmed that neurons in the auditory system that become hyperactive after noise exposure in animals can be modulated by stimulation of the nerves that connect with these muscles. In fact, tinnitus patients often suffer from head and neck muscle defects. Restoring balance to certain muscle groups to turn on the neural pathways underlying the modulatory effect may be able to reduce tinnitus. Future studies are needed to determine if this approach has therapeutic potential.
James A. Kaltenbach, Ph.D., is the director of otology research in the Head and Neck Institute and in the Department of Neurosciences at the Cleveland Clinic.
