For researchers, tinnitus has been a tough nut to crack.
Explore this issue:June 2015
Starting in the mid-1990s, certain surgical cases raised an intriguing question: How can patients who have lost hearing in one ear following tumor excision still “hear” ringing in the deaf ear?
“Intuitively, we knew the answer,” said Richard Salvi, PhD, director of the University at Buffalo’s Center for Hearing and Deafness in New York. When the neural connection between the ear and brain is severed in such patients, it’s impossible for the phantom sound to be generated in the ear, he said. Rather, that signal has to be generated in the brain.
The question is, What parts of the brain are in play?
In a paper published in May 2015, Dr. Salvi and an international team of researchers reported that several interconnected brain structures are involved—far more than previously thought (eLife 2015;4:e06576. DOI: 10.7554/eLife.06576). This “neural network” includes such areas as the amygdala and the reticular formation—the arousal center of the brain that is involved in the “fight or flight” response. The findings offer new insights into why so many patients with tinnitus feel depressed, anxious, or under stress during periods of active disease, Dr. Salvi said.
Some of the implicated brain regions had been identified in earlier, electrophysiologic animal studies that, like the current study, used high doses of aspirin to induce tinnitus and hyperacusis, Dr. Salvi said (Hear Res. 2013;295:100-113). “But some additional regions really lit up in our current study that were quite a surprise to us,” he added.
One such area was the hippocampus. This region of the brain is associated with memory and spatial awareness of sound. “That’s a fascinating finding, because when patients develop tinnitus, they don’t just hear a generalized phantom sound; they’re localizing that sound and say it’s in [the] right or left ear, or in the middle of [their] head, etc. So this finding gives us a neat way of explaining how that localization occurs—it may be mediated by this area of the hippocampus,” he said.
Mapping this neural network could not have been done without the use of functional magnetic resonance imaging (fMRI), Dr. Salvi said. Unlike traditional electrophysiological studies, which tend to focus on only one brain region, fMRIs enable you to look at the functional activity in all parts of the brain simultaneously. “That allowed us to see which regions became active when we stimulated tinnitus in our rat model. It’s a wonderful research tool,” he said.
As for whether that tool can be used to guide future efforts at drug development, “that’s a long way off,” Dr. Salvi stressed. But now that the investigators have identified a neural network as being involved in tinnitus, one future step could well be to figure how to deactivate certain segments of that network, perhaps with drugs that target the neurotransmitters that are involved in the network’s functions, he added.
Tinnitus accounts for billions of dollars in Veterans Administration disability claims each year. In 2014, it was the No. 1 cause for such disability claims, according to the administration’s 2013 Annual Benefits Report. “But because nobody dies from tinnitus, very few research dollars are spent on it,” he said.
Part of that tight-fistedness is due to “a risk-averse drug industry” that is reluctant to fund research for conditions that lack a definitive mechanism of action, Dr. Salvi said. “We may never have that ‘smoking gun’ for tinnitus—it may be a far too heterogeneous condition,” he said. “But we still need to keep trying—especially given the fact that tinnitus continues to cause major disability, especially for combat military personnel and the elderly.”