Identification of the neurophysiological basis of central tinnitus

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Central tinnitus, the perception of sound without any external acoustic stimulus, is a condition with increasing prevalence affecting up to 15% of the adult general population. In severe cases, tinnitus affects a person s ability to lead a normal life, sometimes resulting in the risk of suicide. Still, there is still no cure for such tinnitus. Despite extensive research worldwide it still remains elusive which aspects of neuronal processing actually underlie the phenomenon. A number of different models about the neuronal mechanisms leading to tinnitus are currently discussed, which all have in common that damage to the peripheral receptor epithelium in the cochlea is etiological for the development of the condition, while maladaptive neuroplastic changes within the central auditory system are thought to finally lead to changed neuronal processing within the auditory cortex which then is perceived as tinnitus. Based on our preliminary data, we follow the hypothesis that neuronal activity reflecting tinnitus is characterized by attractor-like spatiotemporal activity patterns within auditory cortex.To describe such attractors, we will measure local field potentials and single-unit spike trains in awake, behaving animals using multichannel microelectrode arrays, and analyze the spatiotemporal activity patterns by means of a self-developed new statistical method for the differentiation of such patterns. According to our hypothesis, in case of subjective tinnitus development (that is induced via noise trauma and evaluated behaviorally and electrophysiologically) the neuronal attractor that can be measured in primary auditory cortex during silence should shift into the location (within an abstract n-dimensional state space, where n equals the number of recording channels) where the stimulus with the same perceptual quality is represented. The reliability of the detection of a tinnitus percept in our experimental animals will be further improved by introducing a new behavioral test.We further aim to demonstrate that such attractors are behaviorally relevant. To this end, we further hypothesize that the perceptual discriminability of two given stimuli depends on the statistical discriminability of their respective attractor representations. To evaluate this hypothesis we will record neuronal activity as described above in animals performing an acoustic discrimination paradigm (shuttle-box training), and statistically compare behavioral performance with simultaneously measured attractor dynamics.In a follow-up proposal, based on the findings of this project, we will develop appropriate training strategies that can be used to systematically shift the attractors within the multi-dimensional state space, thereby changing their perceptual quality. Such techniques will then be used for the development of new therapeutic strategies to treat tinnitus or even other phantom percepts.