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Sounds, Nerve Stimulation Ease Tinnitus Symptoms

January 13, 2011

Researchers have identified a way to ease tinnitus, or ringing in the ears, by stimulating a nerve in the neck while simultaneously playing certain sounds over an extended period of time.  These measures work together to essentially “reboot” the brain, the scientists said.

Tinnitus affects as many as 23 million U.S. adults, including one in 10 seniors and 40 percent of military veterans.  The hallmark of the condition, which is currently incurable, is often a persistent ringing in the ears that ranges in severity from annoying to debilitating.

Similar to pressing a reset button in the brain, the new therapy was found to help retrain the part of the brain in rats that interprets sound, so that errant neurons reverted back to their original state and the ringing disappeared.

“Current treatments for tinnitus generally involve masking the sound or learning to ignore it,” said Dr. James Battey, director of the National Institute on Deafness and Other Communication Disorders (NIDCD), which funded part of the research.

“If we can find a way to turn off the noise, we’ll be able to improve life substantially for the nearly 23 million American adults who suffer from this disorder.”

Tinnitus is a symptom some people experience as a result of hearing loss. When sensory cells in the inner ear are damaged, such as from loud noise, the resulting hearing loss changes some of the signals sent from the ear to the brain. For reasons that are not fully understood, some people will develop tinnitus as a result.

“We believe the part of the brain that processes sounds””the auditory cortex””delegates too many neurons to some frequencies, and things begin to go awry,” said Dr. Michael Kilgard, associate professor of behavior and brain sciences at UT-Dallas, and a co-principal investigator on the study.

“Because there are too many neurons processing the same frequencies, they are firing much stronger than they should be.”

The neurons also fire in sync with one another, and fire more frequently when it is quiet.

Dr. Kilgard said it is these changing brain patterns that produce tinnitus, which is typically a high-pitched tone in one or both ears, although it may also be perceived as clicking, roaring, or a whooshing sound.

Dr. Kilgard, along with co-principal investigator Dr. Navzer Engineer of MicroTransponder, Inc. and others on the research team, first sought to induce changes in the auditory cortex of a group of rats by pairing stimulation of the vagus nerve, a large nerve that runs from the head and neck to the abdomen, with the playing of a single tone.

When stimulated, the vagus nerve releases acetylcholine, norepinephrine, and other chemicals that help promote changes in the brain. The researchers wanted to see if they could induce more brain cells to become responsive to that tone over a period of time.

For 20 days, 300 times a day, researchers played a high-pitched tone, at 9 kilohertz (kHz), to eight rats.  An electrode simultaneously delivered a very small electrical pulse to the vagus nerve.

They found that the number of neurons tuned to the 9 kHz frequency had increased 79 percent in comparison to the control rats.

In a second group of rats, they randomly played two different tones””one at 4 kHz and the other at 19 kHz””but stimulated the vagus nerve only for the higher tone.   The results showed that neurons tuned to the higher frequency increased by 70 percent, while neurons tuned to the 4 kHz tone actually decreased in number.  This indicated that the tone alone was not enough to initiate the change, and that it had to be accompanied by vagus nerve stimulation (VNS).

The researchers then tested whether tinnitus could be reversed in noise-exposed rats by increasing the numbers of neurons tuned to frequencies other than the tinnitus frequency.

One group of noise-exposed rats with tinnitus received VNS that was paired with different tones surrounding the tinnitus frequency 300 times a day for about three weeks.   Rats in the control group received VNS with no tones, tones with no VNS, or no therapy at all.

For both groups, measurements were taken four weeks after noise exposure, then 10 days after therapy began, and one day, one week, and three weeks after therapy ended.

The researchers found that rats that received the VNS paired with tones showed promising results for each time point after therapy began, including midway through therapy, indicating that the ringing had stopped for the treated rats.

Conversely, the results from the control rats indicated their tinnitus had continued throughout the testing period. 

The researchers also followed two treated and two control rats for an additional two months, and found that the treated rats maintained this benefit for more than three months after noise exposure, while the controls continued to be impaired.

An analysis of the neural responses in the auditory cortex in these same rats revealed that neurons in the treated rats had returned to and remained at their normal levels, indicating that the tinnitus had disappeared. However, the control group levels continued to be distorted, indicating that the tinnitus had persisted.

The researchers concluded that the VNS treatment combined with tones had not only reorganized the neurons to respond to their original frequencies, but also made the brain responses sharper, decreased excitability, and decreased synchronization of auditory cortex neurons.

“The key is that, unlike previous treatments, we’re not masking the tinnitus, we’re not hiding the tinnitus. We are retuning the brain from a state where it generates tinnitus to a state that does not generate tinnitus. We are eliminating the source of the tinnitus,” said Dr. Kilgard.

VNS is currently being used to treat some 50,000 people with epilepsy or depression, and MicroTransponder hopes to conduct clinical studies using VNS with paired tones in tinnitus patients.

“The clinical protocol is being finalized now and a pilot study in tinnitus patients will be conducted in Europe in the near future,” said Dr. Engineer, vice president of preclinical affairs at MicroTransponder.

“The support of the NIDCD has been essential to allow our research team to continue our work in this important area of tinnitus research.”

In the meantime, the researchers are working to refine the procedure to better understand details such as the most effective number of paired frequencies to use for treatment, how long the treatment should last, and whether the treatment would work equally well for new tinnitus cases in comparison to long-term cases.

The study was published Wednesday in the advance online publication of the journal Nature.  

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