A new model for tinnitus generation and its therapeutic implications – Tinnitus
According to the World Health Organization, hearing loss represents a major sensory deficit. Indeed, hearing loss is largely prevalent in the general population, and can impair dramatically life quality; its social-economic impact is as great as other public health problems such as alcoholism or lung cancer. The mechanism of noise-induced hearing loss involves the destruction of hair cells in the Organ of Corti within the cochlea and cochlear fibers. Most of cochlear damages are not reversible. Cochlear damages impair the spectro-temporal decomposition of acoustic stimuli and their transduction into a neural signal, leading to a deterioration of speech understanding, especially in noise. Moreover, hearing loss is also causing dramatic changes at virtually all stages of the central auditory system. Importantly, these central changes could induce “aberrant perceptions” such as tinnitus (auditory perception which is not related to any acoustic stimulus in the environment), hyperacusis (overestimation of loudness, namely acoustic stimuli of moderate level are considered as being too loud or painful), and loudness recruitment (an abnormally rapid growth of perceived loudness with sound level). Tinnitus affects an estimated 5% of the general population, and hyperacusis has been reported to be associated to tinnitus in 40% of cases. The main goal of the present project is to challenge in both human subjects and animals an original and synthetic neurophysiological model of tinnitus that we have recently developed. Briefly, this model suggests that inhibition release in auditory centers after loss of input from the cochlea would result in “over-amplification” of neural background noise (residual spontaneous activity in cochlear nerve) and thus give rise to tinnitus. The first aim of the present project is to study in the auditory cortex of guinea pigs the “central gain” whose role is to adapt neural responses to the distribution of sensory inputs. Central gain will be assessed from the input (stimulus amplitude) - output (firing rate) functions obtained from different distribution of intensity levels, in silence, in presence of background noise, before and after noise-induced hearing loss. We will also focus on cortical spontaneous activity (search for a potential neural correlate of tinnitus) and try to relate changes in input-output functions to changes in spontaneous activity. We will use two different and complementary approaches, namely electrophysiology (multi-unit activity and local field potential) and optical imaging with voltage sensitive-dye. The second aim of this project is to test in human subjects the clinical implications of the model. As suggested above, tinnitus could result from the central changes induced by hearing loss. Hearing loss actually causes a decrease of sensory inputs sent towards the auditory centres, or in other words shifts the distribution of sensory inputs towards lower values (i.e. compared to the normal-hearing situation). Therefore, if we could restore a normal distribution of sensory inputs, it could be possible to reverse the central changes induced by hearing loss and ultimately suppress tinnitus. We will study this approach. Our model also states that tinnitus originates from the “amplification” of “neural noise” in the auditory system. The main source of “neural noise” in the central auditory system is the spontaneous activity of cochlear nerve. Therefore, a decrease of this “peripheral drive” could decrease tinnitus. In this context, we will study the effects of extra-cochlear electric stimulation, which is supposed to reduce cochlear nerve activity, on tinnitus. We believe that this project will give further insights into the neurophysiology of the auditory system and tinnitus. This project is also very important as we will test in human subjects a very promising method (extra-cochlear electric stimulation) for suppressing tinnitus.
Monsieur arnaud norena (CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE PROVENCE CORSE) – email@example.com
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
LNIA CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE PROVENCE CORSE
Help of the ANR 200,000 euros
Beginning and duration of the scientific project: - 36 Months