Tinnitus is the persistent perception of a subjective sound, often of high pitch ("ringing of the ears"), which is often a debilitating condition that ruthlessly reduces quality of life for those chronically affected. Estimates of the number of people experiencing tinnitus range from 13% to 18.6% of the general population. The number in the United States alone appears to be upwards of 40 million people. Of those, approximately 10 million experience the effects of tinnitus with such severity that they seek medical attention and 2.5 million are considered disabled as a result of tinnitus. Tinnitus is most often the result of extreme sound exposure. Tinnitus research is critical to the health care needs of the U.S. Armed Forces, their family members, and/or the U.S. veteran population. The facts are disturbing: Tinnitus is the number one service-connected disability from the Global War on Terror. Walter Reed Army Medical Center recently conducted a study of soldiers coming back from Afghanistan and Iraq; the study concluded that of all those exposed to improvised explosive devices, 49% reported tinnitus. In 2006, the Department of Veterans Affairs (VA) reported that nearly 400,000 veterans were on the rolls for service-connected tinnitus disability; this number is expected to increase to 818,811 by 2011.

Despite the prevalence of tinnitus, the pathophysiology of the disorder is poorly understood and, as a result, there is no generally accepted cure, treatment, or prevention method for tinnitus. Our studies are aimed at revealing the cellular and neuronal circuit mechanisms mediating the triggering of tinnitus. How does tinnitus shift from a transient condition to a life-long disorder? Neuronal connections and neuronal activity can change as a result of ongoing sensory experience. This is known as plasticity of the brain. This plasticity can lead to changes in memory or learning, compensation for loss of function, and adaptation to changing demands.

However, plasticity-induced changes can also cause signs and symptoms of disease. Recent studies have shown that individuals with tinnitus have increased neuronal activity in certain areas of the brain, including the auditory brainstem (the first stop of the auditory nerve). We hypothesize that the same cellular and neuronal circuit mechanisms responsible for mediating plasticity in the auditory brainstem may also underlie tinnitus. Tinnitus, after becoming permanent, becomes a perceptual phenomenon and its long-lasting nature involves higher-level structures (including the neocortex). Therefore, the neocortex may represent a better site to target curing tinnitus after becoming permanent.

Additionally, our technical approach is innovative and will significantly advance the fields of tinnitus research and neuroscience significantly. So far, almost all studies focused on cellular changes associated with tinnitus have been performed with extracellular recordings, where underlying mechanisms cannot be studied in great mechanistic detail. Finally, this is the first time that modern imaging techniques for circuit mapping are applied to tinnitus research.

Here, we propose that the auditory brainstem, which represents the first stop of the auditory information in the central nervous system (CNS) and the earliest stage in the auditory CNS where synaptic plasticity occurs, represents the best target for preventing the conversion of transient tinnitus to a chronic disorder. We expect that determining the mechanisms that lead to the triggering of tinnitus will, within the next 3 years, lead to the development of drugs and therapies that can be used soon after the acoustic trauma, thus preventing tinnitus from becoming permanent and irreversible. Such advancement will change the standard of care for tinnitus patients, as most current approaches are focused on the management of tinnitus after it becomes a lifelong disorder. Preventing the development of chronic tinnitus with transient, well-timed therapies will also reduce the side effects of systemic medications as well as the health care costs associated with long-term medical care of tinnitus patients.