London
In rural India, people believe it is the sound of the Gods speaking to them,
and feel blessed. But for most sufferers, the noise is a curse. It has been
likened to air escaping from a bicycle tyre, whistling wind or simply a loud
humming. However they describe it, people with tinnitus come to loathe the
screeching, ringing, buzzing racket that constantly plagues them. They long for
peace and quiet.
Tinnitus affects millions of people worldwide and has been recognised for
thousands of years, yet its origin—somewhere between the ear and
brain— remains hotly debated. However, in the last ten years scientists
have taken some major steps towards understanding the route sound signals
travel. And, at last, they are coming up with new models to explain the source
of the phantom ringing, which might lead to new treatments for stopping the
din.
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Nearly 20 per cent of people in North America and Europe suffer from tinnitus
at some time in their lives, and one in four of them seeks medical help because
they can’t bear the persistent din. There is no single trigger for the
condition. Loud noises, wax in the ear, head injuries and certain drugs can all
start it off, but none is the real reason behind the ringing. “Tinnitus is a
description of a symptom, not a description of a cause,” says Carole Hackney, an
auditory neuroscientist at Keele University.
Counselling and teaching people to cope is the standard treatment for
tinnitus. As a result, it is often seen as a psychological rather than a
physical problem, but some researchers think this could hamper the hunt for a
cure. “There’s been too much focus on getting patients to manage their
tinnitus,” says Jonathan Ashmore, a physiologist at University College London.
Hackney agrees: “It may be all right for those patients who respond to
counselling but what about those people who do not respond? What do we tell
ٳ?”
Tracking down a physical cause will be tricky enough however—never mind
finding a treatment. The auditory system is so complex that the problem could
start in many places (see “Inner space”). Early ideas about the causes of
tinnitus focused on the cochlea, the coiled organ of the inner ear where sounds
are converted into nerve impulses. Most people with severe tinnitus also suffer
hearing loss or are more sensitive to sounds, and researchers concluded that
these were all symptoms of a damaged cochlea.
Ashmore found that high doses of aspirin, known to cause reversible tinnitus
in humans, damage the outer hair cells of the cochlea which amplify sound
signals. And experiments on cats in the 1970s and 1980s seemed to support the
idea that the cochlea was the seat of the problems. “We found that high doses of
aspirin either increased or changed the pattern of electrical activity in the
cochlear nerve,” says Ted Evans, an auditory physiologist at Keele. The trouble
is that people without a cochlea can also suffer from tinnitus—even
cutting the nerve from the cochlea does not stop the ringing in most cases.
Another problem for Evans was that he didn’t know if his animals were
actually experiencing tinnitus. But in 1988 Pawel Jastreboff, then at Yale but
now professor of surgery and physiology at the University of Maryland, found the
answer. He conditioned rats to link silence with fear by giving them a weak
electric shock when he switched off an external buzzing sound. Fear made thirsty
rats stop drinking when things went quiet. Jastreboff found that rats given
aspirin continued to drink even when the buzzing was switched off—the
aspirin was causing tinnitus so the rats did not hear a silence. “They always
said an animal model for tinnitus was a practical impossibility,” says
Jastreboff. But in the latest model, “we can now test hearing loss, behaviour
indicative of tinnitus experience and electrical activity of the auditory
pathways in the same animal.”
The rats also had increased electrical activity in the nerve cells in the
inferior colliculus—a relay station on the auditory pathway that carries
signals from the cochlear nerve to the brain. “This means that tinnitus may not
necessarily originate from the cochlea but at some other point in the auditory
pathway,” Jastreboff says. And in 1996, Jastreboff’s team discovered that loud
noises can also generate bursts of high frequency electrical activity in the
inferior colliculus. Rats exposed to a high intensity tone for 20 minutes
suffered loss of hearing, behaved as though they had tinnitus, and suffered
damage to the outer hair cells of the cochlea. Such damage might be the trigger
for the inferior colliculus activity.
This electrical activity is reminiscent of that seen in the cortex of
patients during a epileptic fit. “This is fascinating,” says Jastreboff.
“Epilepsy can be triggered by certain sounds and some phantom sounds are
associated with epilepsy—but at the moment we can only speculate as to
whether or not these associations are important in the generation of a tinnitus
Բ.”
Following these discoveries, tinnitus researchers are focusing on the
auditory pathways and their activity. Although the pathways carry signals from
external sounds, they never completely shut down, even in total silence. “Just
like other brain pathways, the auditory system is continually active with random
firing of neurons,” says Evans. Such spontaneous activity creates a kind of
background noise that has to be filtered out before the brain registers it as
sound. “We don’t know how and where this filtering actually occurs but we know
from everyday experience that it happens all the time,” says Evans. For example,
we are often oblivious to the constant drone of traffic unless we deliberately
focus on it.
Evans thinks that tinnitus may be caused by a breakdown in this filtering
system. Sufferers constantly hear the background noise in their auditory
pathways. This could explain why tinnitus worsens in a quiet
environment—there is less noise from the outside world to swamp the
background buzz. Background noise might also seep through the normal filtering
mechanisms if the pattern or frequency of the spontaneous signals changes. This
could happen when the cochlea or auditory pathways are damaged.
The story doesn’t end there however. The auditory pathway does not run in
isolation from cochlea to cortex. Other areas of the brain can link up with it,
and modify the signals that reach our consciousness. Ewart Davies, a
pharmacologist at the University of Birmingham, believes that tinnitus may occur
when nerve cells involved in the auditory pathways are damaged, become
“confused” and start making inappropriate connections. “Neurons deprived of an
appropriate input from the cochlea, or from neurons upstream in the auditory
pathway, start sprouting in other directions and making new synapses,” says
Davies. So the signals the brain “hears” may not necessarily travel directly up
the auditory pathway.
Jastreboff now believes that the limbic system—the part of the brain
which deals with emotions—and the autonomic system—which deals with
stress—play prominent roles in the emergence of tinnitus. Support comes
from Alan Lockwood and Richard Salvi in the department of neurology at the State
University of New York, Buffalo. Last year, positron emission tomography
scanning of their tinnitus patients showed increased brain activity in both the
auditory system and the limbic system.
Connections with the limbic and autonomic systems could help explain why
tinnitus becomes intrusive and why anxiety and stressful moods increase the
sensation of tinnitus. “What happens is that people who are continually exposed
to these phantom sounds develop a reaction—annoyance,” says Jastreboff.
“All the time they are being dragged toward the tinnitus signal and so it
becomes a problem.” Counselling helps patients break this vicious downward
spiral.
Jastreboff also thinks that another way to manage tinnitus is to alter a
patient’s perception of the phantom sound. This effectively involves making the
patient’s world noisier. “Increasing [external] background noise may help
tinnitus patients to habituate to their internal sounds and perhaps retrain the
auditory pathway,” say Jastreboff. A noise generator attached to the ear is one
means of therapy, but is usually only effective in conjunction with
psychological treatment.
But altering reactions and perceptions to tinnitus is not a total cure,
according to some researchers. “What we really need is to know what causes
tinnitus and to find a `pill’ to treat the symptom,” says Ross Coles, a
consultant audiological physician in Nottingham and medical advisor to the
British Tinnitus Association.
One line of attack is to find out which neurotransmitters are involved in
sending signals along the auditory pathway. Then drugs could be designed to
block or enhance the signals. “Glutamate and GABA are important
neurotransmitters in the auditory pathway,” says Hackney, “but they are very
common neurotransmitters in the brain.” So, any drug affecting their activities
will also interfere with systems other than the auditory pathway.
Recently the spotlight has turned on GABA as it inhibits the activity of
neurons in the inferior colliculus. “This is a powerful inhibitory
transmitter and could be important in filtering signals which come from the
ear,” says Davies. However, a recent clinical trial carried out by Brian
Westerberg and colleagues at the California Ear Institute, Stanford University,
showed that baclofen, a drug which mimics the effects of GABA, was no more
effective in reducing tinnitus than a placebo.
Davies thinks it is still early days though, and says that there are several
other trials under way on different drugs. He is looking at the effect of an
anti-epileptic drug but the trial is not yet complete.
Jonathan Hazell, a consultant ear surgeon and head of the Royal National
Institute for Deaf People Medical Research Unit in London, is less optimistic.
“The perception of sound can involve every functioning neuron in the auditory
pathway as well as inputs from the limbic system and the autonomic nervous
system,” he says. So trying to find a particular target for drug treatment may
be impossible.
Hazell does believe that tinnitus has a physical cause related to the
detection, filtering and processing of sound signals. But he thinks that
persistent tinnitus only arises in people who begin to focus on weak signals
which normally reach the brain if not the consciousness. “After all tinnitus is
a natural phenomenon,” he says. “Over 90 per cent of the population will
experience tinnitus for short periods of time—after a disco,
perhaps—but they quickly habituate.” In those who do not, Hazell reckons
the tinnitus signal begins to generate an aversive, even phobic response. “I see
tinnitus distress as somewhat similar to arachnophobia,” he says. But people may
learn to ignore the sounds, he believes, after tinnitus retraining therapy.
The disputes over the causes of and treatments for tinnitus seem set to
rumble on for a good while yet. But sufferers need not despair. The rapid growth
of research into our auditory pathways could soon settle these
arguments—and perhaps even lay the phantom sounds to rest for good.
* * *
Inner space
Our auditory system turns sound waves into electrical impulses and transmits
them to the brain, where they are interpreted as what we hear. First, sound
waves hit the eardrum, making it vibrate. Three tiny bones in the middle ear
then pass on the vibrations to the fluid-filled cochlea in the inner ear,
causing fluid movement in this coiled organ. The resulting movement of the hair
cells stimulates the cochlear nerve to send an electrical signal to the brain.
On the way, the signal passes through four relay stations or synapses, known as
the cochlear nucleus complex, the superior olive, the inferior colliculus and
the medial geniculate body, before arriving at its final destination, the
auditory cortex. Each synapse uses chemical transmitters to pass on the signal
from one nerve cell to another.
- Further reading:
Neurophysiological approach to tinnitus patients
by Pawel Jastreboff, William Gray and Susan Gold, American
Journal of Otology, vol 17, p 236-240 (1996)