Fighting noise with noise

Exposure to deafening noise can be, well, deafening. It can also induce incessant ringing in the ears known as tinnitus. But playing tones while pulsing electrical stimulation to the brain could reverse the condition, according to a study on rats published online today (January 12) in Nature.

Image: flickr, gurucrusher/Coty Schwabe

The results are "intriguing," said audiologist linkurl:Richard Tyler;https://www.uihealthcare.com/depts/med/otolaryngology/faculty/tylerbio.html of the University of Iowa Hospitals and Clinics, who was not involved in the research. "If this is a valid model of noise-induced tinnitus, then you'd expect widespread benefits to all kinds of people."Tinnitus, which can be induced not just by loud noises, but also head trauma, certain drugs, and even aging, gives sufferers the sensation of ringing in their ears when no such sound actually exists. The sensation is not imagined. The condition has, in fact, been associated with changes to the auditory cortex of the brain, which impact how sounds are processed. Neurons in this region show an increase in neural excitability, more spontaneous activity, more synchronous firing of neurons, and a general reorganization of the auditory map, with different regions of the cortex firing in response to different sound frequencies. Which of these changes are responsible for the symptoms of tinnitus, however, remains unclear.In an attempt to reverse these neurological changes, neuroscientist Navzer Engineer and other members of linkurl:Michael Kilgard's lab;https://www.utdallas.edu/~kilgard/ at the University of Texas at Dallas worked with rats that experienced mild hearing loss after exposure to extreme noise and appeared to exhibit the symptoms of tinnitus. Specifically, the rats didn't respond to a break in background noise of the same frequency as they were presumably hearing in their heads. Correspondingly, the auditory cortices of these rats were more excitable, fired more synchronously and more spontaneously, and were organized differently than the brains of healthy rats -- more neurons were activated by the tinnitus frequency, while fewer responded to other frequencies in their hearing range. Engineer, now a fulltime employee of linkurl:MicroTransponder Inc.,;https://www.microtransponder.com/ a medical device development company in Austin, Texas, and the team attached an electrode to the vagus nerve (VN) in the rat's neck. The researchers chose VN because it is relatively easy to access, and its stimulation is already used to treat ailments such as epilepsy and depression, meaning that if successful, the treatment could translate well to the clinic. Furthermore, the VN sends electrical signals to the nucleus basalis, a brain region that is more difficult to access, but which has previously proven capable of inducing changes in the auditory cortex's organization when stimulated simultaneously with sounds. The researchers then stimulated the VN with electrical impulses while playing tones higher or lower than the suspected tinnitus frequency. The idea is to train the brain respond more to the paired sounds, and as a result, respond less to the tinnitus frequency, Engineer explained. "We're retuning the brain." Sure enough, the rats exposed to the VN stimulation paired with sounds appeared to recover from their tinnitus, responding once again to the break in the background noise. In addition, many of the neurological changes that resulted from the noise-exposure returned largely to normal: The auditory map was indistinguishable that of non-noise-exposed rats, for example, and the brain became less excitable again, suggesting that these neurological changes may directly influence tinnitus. The synchronous and spontaneous firing of neurons, however, did not correlate with the behavioral changes, suggesting that these measures of tinnitus may not actually be involved in causing the disorder, but further tests are needed to confirm the finding."It's very interesting," said neuroscientist linkurl:Christoph Schreiner;https://keck.ucsf.edu/neurograd/faculty/schreiner.html of the W.M. Keck Center for Integrative Neuroscience at University of California, San Francisco, who was not involved in the research. "This is the most explicit demonstration that plasticity" -- changes to brain organization -- "not only is affected, but can be used for the treatment of potential auditory disabilities."Like all medically-relevant animal studies, the treatment must be tested in people before it can become commercially available. But in this case, there is an additional obstacle: Not everyone is convinced by the animal models of tinnitus. Without comparable human and animal data and without being able to ask the rats whether they have ringing in their ears, "we cannot be sure, as scientists, the animal does in fact have tinnitus," Tyler said.Furthermore, animal models are unable to explore another key aspect of tinnitus, Schreiner said -- its emotional impact. Depression, anxiety, and concentration issues have all been associated with the disorder, but "the loudness of the tinnitus does not relate to how much the patient is distressed by it," he said. "Some people shrug, no big deal, and others are driven nuts and jump off a bridge." Even if this treatment reduces tinnitus, if it doesn't completely eliminate the sound, it might not be an effective treatment for the emotional problems that often come along with tinnitus.Still, "this is a good stepping stone," Tyler said. "It's an exciting step forward, and it will be interesting to see what happens with the humans."N.D. Engineer, et al., "Reversing pathological neural activity using targeted plasticity," Nature, doi:10.1038/nature09656, 2010.
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