Gapless man:machine interface in the inner ear

Over 5% of the world population, 360 Million people, suffer from disabling hearing loss. In severe forms, the auditory function can be restored by a neuroprostheses called cochlear implant (CI), which functionally replaces lost inner ear sensory cells by directly stimulating the auditory nerve fibers. Despite the success of these devices, some limitations remain, including suboptimal auditory resolution and high energy consumption, which are mainly due to the anatomical gap between the implanted electrode array in the cochlea and the auditory neurons nearby. Within a recently completed, multinational EU FP7 project coordinated by the main applicant (www.nanoci.org), proof of principle for overcoming the anatomical gap by guided growth of auditory nerve fibers towards the electrode array has been obtained in vivo. In addition, in vitro experiments have shown a potential reduction of the stimulus energy by a factor of 5, if the distance of the auditory neurons from the electrode was eliminated. Within the proposed project we intend to improve the gapless interface through optimized growth factor guidance in combination with chronic electrical stimulation and detailed morphological, molecular and electrophysiological characterization of regrown auditory neurons in vitro and in vivo. Native and stem cell generated, donated human auditory neurons will be used in vitro for validation. The ultimate goal of the proposed project is to assess the potential of the gapless interface between auditory neurons and the cochlear implant electrodes through chronic electrical stimulation in vivo. If successful, the proposed project may lead to more energy efficient cochlear implant systems with higher auditory resolution and improved sound quality.

Gapless man:machine interface in the inner ear Profound loss of speech understanding or deafness can be restored with a cochlear implant, a neuroprosthesis that functionally replaces sensory cells by directly stimulating the cochlear nerve electrically. An audio processor with a microphone converts sound into electrical signals and transmits them to an electrode with 12-36 channels which is inserted into the cochlea. Despite the success of these devices over more than four decades, fidelity of hearing is limited and energy consumption high. The main reason is the anatomical gap between the implanted electrode array and the auditory neurons nearby. The multinational project with three involved partners from Geneva, Tuebingen and Innsbruck aimed to close this gap by stimulating the growth of nerve fibres towards the stimulating electrode. Neurotrophins, small proteins that trigger signals in auditory neurons have been shown to enhance survival and boost nerve fibre outgrowth. We used novel self-developed auditory neuron mature-like cell cultures and auditory neuron explant cultures to find the best concentration and ideal mix of neurotrophins and tested whether different kinds of electrical stimulation are beneficial during the outgrowth phase. Further, deaf guinea pigs were implanted with animal cochlear electrodes and the optimized neurotrophic cocktail applied as a gel to validate our findings from culturing in vivo. Results show that neurotrophins promote auditory neuron outgrowth considerably and establish mature nerve fibres in-vivo. A cellular matrix where nerve fibres can grow on is absolutely necessary. In most cases of cochlear implantation, we anyway observe a reaction of connective tissue growth around the electrode that regrowing nerve fibres can use as a "street". We found optimal concentrations and the best mix of neurotrophins. Fortunately, the range of beneficial concentrations is so wide that the high concentration gradient that forms when we put drugs into the inner ear should not be a problem at all. Electrical stimulation during the outgrowth phase decreases number and length of regrown nerve fibres, so we cannot recommend it. The long-term maintenance of loose connective tissue around the electrode that does not compactify or turn into bone is still a task to be solved. Our joint project brought us closer to the implementation of a bioactive cochlear implant that attracts auditory nerve fibres to directly integrate with the cochlear implant electrode. Hundreds of independent channels would dramatically increase the quality of "electrical" hearing.