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10 research teams

Cognition et communication 
auditive

Dirigée par Luc Arnal & Diane Lazard

Code neural dans le système auditif

Dirigée par Jérémie Barral

Dynamique du système auditif et perception multisensorielle

Dirigée par Brice Bathellier

Exploration clinique et translationnelle des synaptopathies auditives

Dirigée par Didier Dulon & Hung Thai-Van

Code neural dans le système auditif

Dirigée par Jérémie Barral

Code neural dans le système auditif

Dirigée par Jérémie Barral

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Our workpackages

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New Treatments and handling of sudden and fluctuating deafness

Chairman: Paul AVAN, IHU reConnect WP1 Leader

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New Treatments and handling of sudden and fluctuating deafness

ABSTRACT GABAergic inhibition has been suggested to be affected in tinnitus. Several animal studies showed that deficient GABAergic inhibition is associated with behavioral evidence of tinnitus. In addition, MR spectroscopy performed in humans found a decreased GABA concentration in the auditory cortex of participants with tinnitus. We further investigated the role of GABA using PET-scans in humans. A flumazenil tracer was used, that binds to GABA receptors in the brain. We found an increased GABA receptor availability in the auditory cortex of participants with tinnitus. Possibly, the increased availability of receptors is a consequence of a reduction of the GABA concentration. Alternatively, homeostatic upregulation of GABA receptors may have occurred to mitigate neuronal hyperactivity in auditory neurons. These results unequivocally establish a key role of GABA inhibition in tinnitus and may inform further research into pharmaceutical interventions for tinnitus.

New treatments handling of deafness

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New Treatments and handling of sudden and fluctuating deafness

ABSTRACT This talk will explore how multimodal neuroimaging integrates different biomarkers to improve the diagnosis and differentiation of neurodegenerative diseases, using advanced combinations of MRI, FDG-PET, and amyloid PET. Recent diagnostic algorithms suggest optimal sequencing of these techniques for greater specificity and sensitivity. The second focus is on understanding disease mechanisms, such as disconnection syndromes and lesion propagation, which provide insights into AD pathophysiology. Emerging imaging modalities, including dual-phase PET and AI-enhanced analysis, pave the way for personalized prediction of disease trajectories and future therapeutic strategies.

Workpackage 1

New Treatments and handling of sudden and fluctuating deafness

ABSTRACT This talk will explore how multimodal neuroimaging integrates different biomarkers to improve the diagnosis and differentiation of neurodegenerative diseases, using advanced combinations of MRI, FDG-PET, and amyloid PET. Recent diagnostic algorithms suggest optimal sequencing of these techniques for greater specificity and sensitivity. The second focus is on understanding disease mechanisms, such as disconnection syndromes and lesion propagation, which provide insights into AD pathophysiology. Emerging imaging modalities, including dual-phase PET and AI-enhanced analysis, pave the way for personalized prediction of disease trajectories and future therapeutic strategies.

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New Treatments and handling of sudden and fluctuating deafness

ABSTRACT Approximately 10-15% of the population perceive simple sounds in the absence of any identifiable external source, a phenomenon commonly referred to as tinnitus. Although often associated with hearing damage, no consistent aberrant peripheral signal has been found to explain this sensation. Consequently, over the past two decades, research efforts have increasingly focused on identifying abnormal brain activity as a potential cause. However, no reliable “neural “of tinnitus has been identified to date. Against this backdrop, my presentation will provide an overview of recent research in my group aimed at better understanding how brain activity relates to tinnitus. This includes a fresh perspective on “resting state“ activity and efforts to investigate predictive processing in tinnitus.

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Characterizing and treating Auditory Perception Disorders

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Chairman: Sophie BOUTON, IHU reConnect WP5 Leader

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New Treatments and handling of sudden and fluctuating deafness

ABSTRACT Soundscenes are three-dimensional, and a critical aspect of hearing is that we can not only pinpoint what a source is, but from where it originates. Sound localisation is not only crucial for survival, but is essential for listening effectively in background noise. In this talk I will synthesise a number of studies from our lab that seek to understand how auditory spatial perception arises in auditory cortex. The spatial location of a sound source must be reconstructed from sound localization cues, principally available through the comparison of the timing and level of the sound at the two ears. These cues are extracted by dedicated brainstem nuclei, but, at least in primates and carnivores, auditory cortex is required for sound localisation. By recording in freely moving ferrets we were able to explore how neurons map sounds across coordinate frames to provide both head-centred and head-independent representations of sound source location. In addition to encoding sound localisation we have also uncovered a variety of sensory and motor related signals.

Hearing and dementia

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New Treatments and handling of sudden and fluctuating deafness

ABSTRACT The ability to recognize and interpret sounds is essential for both humans and increasingly so for machines. From the melodic chirping of birds to the urgent wails of passing emergency vehicles, sound perception allows us to comprehend events and identify objects, even in darkness or behind barriers. This presentation describes interdisciplinary research across cognitive psychology, neuroscience, and artificial intelligence (AI) to explore contemporary models elucidating how the human brain processes real-world sounds and scenes. It investigates the neural mechanisms by which acoustic waveforms are transformed into meaningful semantic representations, shedding light on higher-level auditory cognition. Additionally, this talk examines potential collaborative endeavors between AI and cognitive neuroscience, aiming to deepen our understanding of the neural computations involved in extracting diverse semantic information from auditory stimuli.

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Chairman: Aziz EL AMRAOUI, IHU reConnect WP9 Leader

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New Treatments and handling of sudden and fluctuating deafness

ABSTRACT It is unknown how the human and rodent auditory cortices develop distinct communication processing capabilities. Decoding auditory signals is a challenging task due to the fleeting nature of the auditory scene. From humans to mice, one strategy believed to be important in decoding auditory signals is distributing the computational load between the left and right Auditory Cortices (i.e., lateralization). The circuitry underlying these sound-processing tasks is most receptive to refinement during critical periods when the brain is shaped by neural activity reflecting sensory information in the current environment. We hypothesize that asynchronous timing of critical periods between hemispheres may serve as a key mechanism underlying the development of functional specializations. To investigate, we compared measures of thalamocortical and intracortical maturation that have been previously associated with critical periods in sensory cortices. Our findings revealed that the transition from immature to mature patterning in thalamocortical activation of the left auditory cortex lags behind that of the right auditory cortex. Additionally, indicators of inhibitory and excitatory synapse development showed earlier maturation in the right auditory cortex. To evaluate the functional relevance of this asynchronous maturation between the auditory cortices, we manipulated the acoustic environment of male and female juvenile mice and tested the impact on tonotopic map re-arrangement in adulthood. Notably, tone rearing male mice resulted in tone overrepresentation in the right Auditory Cortex, while tone rearing within the same time window led to the opposite trend in females, with overrepresentation in the left auditory cortex. These findings suggest that differential timing in hemisphere development could precipitate lateralized auditory functioning in a sex-specific manner. Using spatial transcriptomics, we aim to uncover the molecular pathways that may coordinate asynchronous maturation between the hemispheres and how they are disrupted in neuropsychiatric disorders.

Hearing : Network and data science

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New Treatments and handling of sudden and fluctuating deafness

ABSTRACT Hearing loss is the most common sensory deficit worldwide, affecting millions of individuals. Hearing impaired people are severely handicapped in our modern society that heavily relies on fast communication. Half of the cases with congenital hearing loss have a genetic origin. Although hearing aids and cochlear implants have significantly improved over time, they still cannot compete with natural hearing. Several types of genetic therapies are currently being evaluated, each having their own advantages and drawbacks. Our main focus is the development of RNA therapies, using antisense oligonucleotides (ASOs). ASOs are small single-stranded oligo’s that are complementary to (pre-)mRNA that can have different chemistries and modifications. Their chemical composition determines stability, mode of action, specificity and affinity for their target sequence. ASOs can be used in different flavors to modulate pre-mRNA splicing or to induce the allele-specific degradation of transcripts. The main focus of our research are Usher syndrome type 2 and two dominantly inherited form of non-syndromic hearing loss (DFNA9/DFNA21). For combatting Usher syndrome, we have developed a pipeline consisting of different models, long-read sequencing approaches and bio-informatic tools to predict and functionally assess suitable splice modulation targets based on a patient’s genotype. Furthermore, we have developed allele-specific gapmer ASOs to degrade mutant transcripts associated with late-onset dominantly inherited forms of hearing loss DFNA9 and DFNA21, for which mutations act via a non-haploinsufficiency disease mechanism. Challenges remain, including development of methods that enable repeated delivery and a cost-effective translation of preclinical findings into a clinical application for (ultra)rare conditions.

Hearing : Connected research and medicine (CoReMed, WP7)

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New Treatments and handling of sudden and fluctuating deafness

Hearing : Connected research and medicine (CoReMed, WP7)
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