Auditory neuropathy impairs speech comprehension severely, beyond the extent that would be expected on the basis of increased threshold of audibility
Auditory neuropathy encompasses a range of disease mechanisms that typically disrupt the synaptic encoding and/or neural transmission of auditory information in the cochlea and auditory nerve
Auditory synaptopathy, impaired sound encoding at the synapses between inner hair cells and spiral ganglion neurons, results from genetic defects or insults such as exposure to loud noise
Advanced physiological and psychophysical testing combined with molecular genetic analysis facilitate diagnostics of auditory synaptopathy and neuropathy
Although traditional hearing aids often do not provide substantial benefit for patients with auditory synaptopathy or neuropathy, cochlear implants can provide effective hearing rehabilitation depending on the site(s) of disorder
Sensorineural hearing impairment is the most common form of hearing loss, and encompasses pathologies of the cochlea and the auditory nerve. Hearing impairment caused by abnormal neural encoding of sound stimuli despite preservation of sensory transduction and amplification by outer hair cells is known as 'auditory neuropathy'. This term was originally coined for a specific type of hearing impairment affecting speech comprehension beyond changes in audibility: patients with this condition report that they “can hear but cannot understand”. This type of hearing impairment can be caused by damage to the sensory inner hair cells (IHCs), IHC ribbon synapses or spiral ganglion neurons. Human genetic and physiological studies, as well as research on animal models, have recently shown that disrupted IHC ribbon synapse function — resulting from genetic alterations that affect presynaptic glutamate loading of synaptic vesicles, Ca2+ influx, or synaptic vesicle exocytosis — leads to hearing impairment termed 'auditory synaptopathy'. Moreover, animal studies have demonstrated that sound overexposure causes excitotoxic loss of IHC ribbon synapses. This mechanism probably contributes to hearing disorders caused by noise exposure or age-related hearing loss. This Review provides an update on recently elucidated sensory, synaptic and neural mechanisms of hearing impairment, their corresponding clinical findings, and discusses current rehabilitation strategies as well as future therapies.
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The authors declare no competing financial interests.
- Auditory neuropathy
A hearing impairment found in individuals with hereditary motor and sensory neuropathy; impairs speech comprehension beyond what would be expected on the basis of pure tone audiograms.
- Ribbon synapses
Highly specialized synapses between the inner hair cells and spiral ganglion neurons, with an electron-dense structure — the synaptic ribbon — at the presynaptic active zone that mediates neurotransmitter release.
- Cochlear microphone potentials
Outer hair cells generate local cochlear potentials that follow the sound stimulus so precisely that they are called 'microphone potentials'.
- Otoacoustic emission
Sound generated from within the inner ear that can be measured with a sensitive microphone in the external ear canal to assess outer hair cell function.
- Auditory brainstem responses
Evoked potentials in response to repetitive acoustic stimulation that are recorded from scalp EEG electrodes and typically have five peaks, referred to as waves I–V.
- Spiral ganglion compound action potential
The first auditory brainstem response peak, wave I, reflects the spiral ganglion compound action potential; this potential can be recorded with better resolution using electrocochleography.
- Auditory synaptopathy
Hearing impairment caused by dysfunction or loss of ribbon synapses in the inner hair cells; has been termed auditory synaptopathy and can show clinical findings similar to those described above for auditory neuropathy.
- Organ of Corti
The organ of Corti is the end organ of the sense of hearing that harbours the sensory inner and outer hair cells, as well as afferent and efferent nerve fibres and various types of supporting cells.
- Compound action potential
Reflects the synchronized firing of spiral ganglion neurons; assessed by intrameatal or transtympanic electrocochleography.
- Glutamate excitotoxicity
Excessive presynaptic glutamate release leading to massive depolarization and subsequent synapse loss.
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Moser, T., Starr, A. Auditory neuropathy — neural and synaptic mechanisms. Nat Rev Neurol 12, 135–149 (2016). https://doi.org/10.1038/nrneurol.2016.10
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