Responses from Dr Roland Schaette, British Tinnitus Association’s Senior Research Associate at the UCL Ear Institute in London How close are we to finding a cure for tinnitus? At the moment, we are closer than ever to finding a cure for tinnitus. In the past decade, tinnitus research has made tremendous progress, and we have learned a lot about the mechanisms that are involved in the development of tinnitus. A very significant part of the progress has come from a switch of perspective: although tinnitus can be triggered in the ear, the processes that keep it going and make it a problem are in the brain.,so tinnitus can be approached from a neuroscience perspective. This broadened scope has attracted the interest of brain researchers towards tinnitus, and today more research groups than ever before are involved in tinnitus research. The picture of the mechanisms that lead to the development of tinnitus has become much clearer. I thus expect that the puzzle of how tinnitus arises will be solved within the next decade, and that this will lead to true targeted tinnitus treatments. Why has clinical research so far failed to identify a cure? In the past, the major obstacle blocking the way towards a cure was that our understanding of how tinnitus arises had been quite limited. Especially, it was unknown which mechanisms in the brain lead to the persistent, aberrant nerve cell activity that underlies the perception of the phantom sound. Without a thorough understanding of these issues, the potential targets for tinnitus treatments were unclear. However, a clearer picture of the mechanisms of tinnitus development has been emerging in the last decade, and this could form the basis for new targeted approaches towards tinnitus treatment in the not too distant future. What do we know and what don't we know about tinnitus? It is now well established that tinnitus is generated in the brain and not in the ear. Moreover, we have learned from animal studies that tinnitus might be linked to increased spontaneous activity of nerve cells in the brain. The development of this pathological hyperactivity can be triggered for example by hearing loss. What we do not know yet is how this happens exactly, i.e. which functional mechanisms in the brain are responsible for the observed changes. However, several candidate mechanisms have been identified recently, and we have also come closer to understanding where exactly in the auditory system these changes take place. What research is currently being done at UCL? At the UCL Ear Institute, we pursue an integrated approach to tinnitus research that comprises data collection from tinnitus patients, animal experiments to study in detail the mechanisms of tinnitus development, and computer modeling to derive a comprehensive theory of tinnitus development. We believe that all these building blocks are necessary to gain a thorough understanding of tinnitus, as they form a closed loop: the data we collect from humans and animals is used to advance our computer model of tinnitus, and the predictions from the model inspire new experiments. A recent success of this strategy has been that we could validate a specific prediction of the computer model, when we found physiological evidence for cochlear damage even in tinnitus patients with a normal audiogram. To what extent is the British Tinnitus Association funding/contributing to finding a cure? Even though the in the UK alone there are more than a million tinnitus sufferers, it is difficult to obtain funding for tinnitus research, and the number of research groups that focus on understanding this condition has therefore remained relatively small. Funding from a dedicated charity like the BTA thus makes a huge difference. The BTA has funded a post for a Senior Research Associates research at the UCL Ear Institute, where this position has acted as a “condensation nucleus” for dedicated tinnitus research, and thus the BTA has helped to establish a whole new program of research into how tinnitus arises and how it might be cured. Since the post was established two years ago, we have managed to provide new evidence for a common mechanism for the development of tinnitus with and without apparent hearing loss, providing an important piece to the puzzle of the genesis of tinnitus. What has been discovered in the last 12 months, and how has this improved understanding about tinnitus? In most cases, tinnitus is associated with hearing loss, and how damage to the inner ear might trigger the development of tinnitus has been studied in great detail. However, a substantial fraction of tinnitus patients has a normal audiogram, and it has been an open question whether tinnitus is caused by the same mechanism in that case, or whether we are dealing with different pathologies that just give rise to the same symptom. We could now provide physiological evidence that also tinnitus patients with a normal audiogram have a certain kind of damage to structures of the inner ear, and our computer model predicts that this kind of damage could act as a trigger for tinnitus. Moreover, our data also indicate that plastic changes that might be involved in the generation of tinnitus already take place in the early processing stages of the auditory system. We have thus come a lot closer to identifying and localising the processes that lead to tinnitus. What further research would you like to undertake in this area? In the next year, we firstly plan to continue our data collection from tinnitus patients. Secondly, we want to study the mechanisms of tinnitus development in more detail in animal experiments, and we will specifically tailor the experiments to match the characteristics of our human data. In that way, we can observe directly in the brain how the nerve cell activity changes in a situation that resembles human tinnitus as closely as possible. Finally, we will use our computer model to simulate different treatment approaches to cure tinnitus “in silico”, which will help us identify new approaches to tinnitus treatment. We hope that this integrated approach, spanning all the levels from basic to clinical research, will significantly speed up the search for a cure for tinnitus. About Dr Roland Schaette Roland studied Biophysics in Berlin and Zurich. He then returned to Berlin where he did a PhD on Tinnitus and continued working there as a postdoc before starting work at the Ear Institute.