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Liaison in Scientific Training for European auditory Neuroscience

Periodic Reporting for period 2 - LISTEN (Liaison in Scientific Training for European auditory Neuroscience)

Reporting period: 2018-12-01 to 2020-11-30

Hearing loss is a rapidly expanding health concern, which has a devastating social impact, reducing our ability to have a conversation in noisy environments, and consigning the deaf to social isolation. Hearing loss can have other debilitating consequences, as sufferers begin to hear phantom sounds; these are loud, distracting and imaginary sounds, known as tinnitus. Although tinnitus is typically preceded by hearing loss, it is usually not generated in the ear, but is ‘created’ by the brain. The general consensus is that tinnitus results from abnormal excitability in the central auditory system, but neither the location of the problem nor the exact plasticity processes underlying tinnitus are well understood.
The LISTEN (Liaison In Scientific Training for European auditory Neuroscience) training network consisted of European auditory neuroscientists working with several European companies to improve hearing aids (including cochlear implants) and pharmacological treatments for tinnitus and hearing loss.
The overall objectives for LISTEN were:
1) To elucidate how the auditory system encodes complex sounds, both in normal and compromised hearing.
2) To study the underlying mechanisms of tinnitus, and test possible pharmacological treatments.
3) To train 10 ESRs to acquire technical skills and broader knowledge necessary in modern neuroscience research, while also learning to relate and translate their work for industrial and clinical applications.
The LISTEN project has led to new, fundamental insights into the question how the auditory system deals with the large range of sound intensities and sound frequencies it has to encode, how attention can modulate the encoding of the location of sounds, or the way the brain detects novel sounds. Moreover, mechanisms underlying different forms of hearing loss were elucidated, and some of the functional changes in the brain that occur in tinnitus were studied in detail. Finally, the LISTEN project has successfully trained 10 ESRs as auditory neuroscientists, which either have defended their thesis or are preparing to do so this year.
The first work package aimed to elucidate how the auditory system encodes complex sounds, both in normal and compromised hearing. The main results obtained during the LISTEN project were:
-To investigate how the inner ear encodes complex sounds a novel imaging technique called Optical Coherence Tomography (OCT) was established. This technique allows to study sound-induced movements in inner ear structures that were previously inaccessible. This technique allowed to define much better which structures in the inner ear are responsible for the decoding of complex sounds.
-To better understand how complex sounds are encoded in the brain, recordings from different auditory (inferior colliculus) and non-purely auditory (medial prefrontal cortex) regions were made. It was found that some cells can encode deviant sounds, i.e. sounds that had not been played in the recent history. These findings advanced in the understanding of the cellular mechanisms that allow discriminating changes in the environment, which are inaccessible in human research.
-The establishment of a technique that uses light to activate a defined set of auditory neurons in mice. This allowed to test to what extent optical stimulation can substitute for the auditory percept, leading to a better understanding of what an auditory percept constitutes. These studies therefore contribute to the scientific basis for the future development of prostheses based on direct activation of the central auditory system in hearing-impaired.
-a task has been designed that allows to study whether attention changes how the location of where sounds come from is encoded in the auditory cortex.
The second work package aims to study the underlying mechanisms of tinnitus, and test possible pharmacological treatments. Some of the examples of the progress obtained during the project are:
-A better understanding of the underlying cause for a form of progressive hearing loss in humans was obtained by studying the inner ear of a mouse model for this disease.
-A new method was developed to suppress the activity of potassium channels using light in a transgenic mouse. Potassium channels are very important for controlling excitability in neurons, and changes in excitability are thought to underlie tinnitus. This method will allow us to study the impact of potassium channels on excitability in a much more controlled way than by classical, pharmacological methods.
-Some of the cellular changes underlying tinnitus induced by high doses of salicylate, the active ingredient in aspirin, were characterized. These results can be used as the basis for studying the cellular mechanisms underlying other forms of tinnitus, including those that follow hearing loss.
-Several mouse models that showed unusual responses to sound, thought to be characteristic of the presence of tinnitus, were studied in detail, in order to better understand the underlying molecular and cellular changes. The observed abnormal responses to complex sounds give us insights that will allow a more precise diagnosis of different types of hearing impairments in humans.
An important part of this ITN has been devoted to training. Apart from a five-week summer course on Auditory Neuroscience, a large number of workshops were organized to train the ESRs in a variety of techniques and topics. An important part of the training involved secondments, in which new techniques and methods were learned from other laboratories within the LISTEN consortium. Each ESR did at least one secondment at another laboratory in an academic or industrial setting. The first scientific papers summarizing the results have already been published, and additional papers are in preparation. Most ESRs were able to present their results to the public and at scientific meetings, even though the Covid crisis led to the cancellation of all public outreach events that were planned in the final year and many scientific conferences.
Even though the Covid crisis led to substantial delays in the work in the laboratories involved in the LISTEN project, the project has been able to meet its original goals. In LISTEN, multiple laboratories with specialist skills have trained 10 ESRs as auditory neuroscientists, with a focus on the alterations in perception in subjects suffering from hearing loss and tinnitus. The consortium has obtained new, fundamental insights into how complex sounds are decoded by the brain, and how this changes in hearing-impairment. It has come up with an evaluation of the methods to detect these changes, and suggestions for both improvements in existing methods for hearing restoration, but also new methods to directly change the activity of the auditory system. Moreover, the work performed in LISTEN has provided a better understanding of the underlying mechanisms of tinnitus, which will hopefully help to improve treatment for this common and debilitating condition in the future.
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