Auditory neuropathy--neural and synaptic mechanisms.

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".

Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy.

The effects of inner ear abnormality on audibility have been explored since the early 20th century when sound detection measures were first used to define and quantify 'hearing loss'. The development in the 1970s of objective measures of cochlear hair cell function (cochlear microphonics, otoacoustic emissions, summating potentials) and auditory nerve/brainstem activity (auditory brainstem responses) have made it possible to distinguish both synaptic and auditory nerve disorders from sensory receptor loss. This distinction is critically important when considering aetiology and management.

Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations.

Mutations in the OTOF gene encoding otoferlin result in a disrupted function of the ribbon synapses with impairment of the multivesicular glutamate release. Most affected subjects present with congenital hearing loss and abnormal auditory brainstem potentials associated with preserved cochlear hair cell activities (otoacoustic emissions, cochlear microphonics [CMs]). Transtympanic electrocochleography (ECochG) has recently been proposed for defining the details of potentials arising in both the cochlea and auditory nerve in this disorder, and with a view to shedding light on the pathophysiological mechanisms underlying auditory dysfunction.

Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome.

Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.

Auditory neuropathy.

Neural disorders of the auditory nerve are associated with particular disorders of auditory perceptions dependent on processing of acoustic temporal cues. These include: (1) speech perception; (2) localizing a sound's origin in space; and (3) identifying sounds in background noise. Auditory neuropathy (AN) is a consequence of: (1) presynaptic disorders affecting inner hair cell ribbon synapses; (2) postsynaptic disorders of auditory nerve dendrites; and (3) postsynaptic disorders of auditory nerve axons.

Cortical Activity during Perception of Musical Rhythm; Comparing Musicians and Non-musicians.

This study investigates the effects of musical training on brain activity to violations of rhythmic expectancies. We recorded behavioral and event-related brain potential (ERP) responses of musicians and non-musicians to discrepancies of rhythm between pairs of unfamiliar melodies based on Western classical rules. Rhythm deviations in the second melody involved prolongation of a note, thus creating a delay in the subsequent note; the duration of the second note was consequently shorter because the offset time was unchanged.

Review of hair cell synapse defects in sensorineural hearing impairment.

Objective: To review new insights into the pathophysiology of sensorineural hearing impairment. Specifically, we address defects of the ribbon synapses between inner hair cells and spiral ganglion neurons that cause auditory synaptopathy.

Data Sources And Study Selection: Here, we review original publications on the genetics, animal models, and molecular mechanisms of hair cell ribbon synapses and their dysfunction.

Loudness adaptation accompanying ribbon synapse and auditory nerve disorders.

Abnormal auditory adaptation is a standard clinical tool for diagnosing auditory nerve disorders due to acoustic neuromas. In the present study we investigated auditory adaptation in auditory neuropathy owing to disordered function of inner hair cell ribbon synapses (temperature-sensitive auditory neuropathy) or auditory nerve fibres. Subjects were tested when afebrile for (i) psychophysical loudness adaptation to comfortably-loud sustained tones; and (ii) physiological adaptation of auditory brainstem responses to clicks as a function of their position in brief 20-click stimulus trains (#1, 2, 3 … 20).

Auditory cortical activity in normal hearing subjects to consonant vowels presented in quiet and in noise.

Objective: Compare brain potentials to consonant vowels (CVs) as a function of both voice onset times (VOTs) and consonant position; initial (CV) versus second (VCV).

Methods: Auditory cortical potentials (N100, P200, N200, and a late slow negativity, (SN) were recorded from scalp electrodes in twelve normal hearing subjects to consonant vowels in initial position (CVs: /du/ and /tu/), in second position (VCVs: /udu/ and /utu/), and to vowels alone (V: /u/) and paired (VVs: /uu/) separated in time to simulate consonant voice onset times (VOTs).

Results: CVs evoked "acoustic onset" N100s of similar latency but larger amplitudes to /du/ than /tu/.

Spatiotemporal distribution of cortical processing of first and second languages in bilinguals. I. Effects of proficiency and linguistic setting.

The study determined how spatiotemporal distribution of cortical activity to words in first and second language is affected by language, proficiency, and linguistic setting. Ten early bilinguals and 14 late adult bilinguals listened to pairs of words presented in Arabic (L1), Hebrew (L2), or in mixed pairs and indicated whether both words had the same meaning or not. Source current densities of event-related potentials were estimated.

Spatiotemporal distribution of cortical processing of first and second languages in bilinguals. II. Effects of phonologic and semantic priming.

This study determined the effects of phonology and semantics on the distribution of cortical activity to the second of a pair of words in first and second language (mixed pairs). The effects of relative proficiency in the two languages and linguistic setting (monolinguistic or mixed) are reported in a companion paper. Ten early bilinguals and 14 late bilinguals listened to mixed pairs of words in Arabic (L1) and Hebrew (L2) and indicated whether both words in the pair had the same or different meanings.

Auditory processing deficits in individuals with primary open-angle glaucoma.

Objective: The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma.

Tinnitus suppression by low-rate electric stimulation and its electrophysiological mechanisms.

Tinnitus is a phantom sensation of sound in the absence of external stimulation. However, external stimulation, particularly electric stimulation via a cochlear implant, has been shown to suppress tinnitus. Different from traditional methods of delivering speech sounds or high-rate (>2000 Hz) stimulation, the present study found a unique unilaterally-deafened cochlear implant subject whose tinnitus was completely suppressed by a low-rate (<100 Hz) stimulus, delivered at a level softer than tinnitus to the apical part of the cochlea.

Auditory cortical N100 in pre- and post-synaptic auditory neuropathy to frequency or intensity changes of continuous tones.

Objectives: Auditory cortical N100s were examined in ten auditory neuropathy (AN) subjects as objective measures of impaired hearing.

Methods: Latencies and amplitudes of N100 in AN to increases of frequency (4-50%) or intensity (4-8 dB) of low (250 Hz) or high (4000 Hz) frequency tones were compared with results from normal-hearing controls. The sites of auditory nerve dysfunction were pre-synaptic (n=3) due to otoferlin mutations causing temperature sensitive deafness, post-synaptic (n=4) affecting other cranial and/or peripheral neuropathies, and undefined (n=3).

A comparison of auditory evoked potentials to acoustic beats and to binaural beats.

The purpose of this study was to compare cortical brain responses evoked by amplitude modulated acoustic beats of 3 and 6 Hz in tones of 250 and 1000 Hz with those evoked by their binaural beats counterparts in unmodulated tones to indicate whether the cortical processes involved differ. Event-related potentials (ERPs) were recorded to 3- and 6-Hz acoustic and binaural beats in 2000 ms duration 250 and 1000 Hz tones presented with approximately 1 s intervals. Latency, amplitude and source current density estimates of ERP components to beats-evoked oscillations were determined and compared across beat types, beat frequencies and base (carrier) frequencies.

Mutation of OPA1 gene causes deafness by affecting function of auditory nerve terminals.

Autosomal dominant optic atrophy (DOA) is a retinal neuronal degenerative disease characterized by a progressive bilateral visual loss. We report on two affected members of a family with dominantly inherited neuropathy of both optic and auditory nerves expressed by impaired visual acuity, moderate pure tone hearing loss, and marked loss of speech perception. We investigated cochlear abnormalities accompanying the hearing loss and the effects of cochlear implantation.

Abnormal cochlear potentials from deaf patients with mutations in the otoferlin gene.

Otoferlin is involved in neurotransmitter release at the synapse between inner hair cells (IHCs) and auditory nerve fibres, and mutations in the OTOF gene result in severe to profound hearing loss. Abnormal sound-evoked cochlear potentials were recorded with transtympanic electrocochleography from four children with otoferlin (OTOF) mutations to evaluate physiological effects in humans of abnormal neurotransmitter release from IHCs. The subjects were profoundly deaf with absent auditory brainstem responses and preserved otoacoustic emissions consistent with auditory neuropathy.

Cortical evoked potentials to an auditory illusion: binaural beats.

Objective: To define brain activity corresponding to an auditory illusion of 3 and 6Hz binaural beats in 250Hz or 1000Hz base frequencies, and compare it to the sound onset response.

Methods: Event-Related Potentials (ERPs) were recorded in response to unmodulated tones of 250 or 1000Hz to one ear and 3 or 6Hz higher to the other, creating an illusion of amplitude modulations (beats) of 3Hz and 6Hz, in base frequencies of 250Hz and 1000Hz. Tones were 2000ms in duration and presented with approximately 1s intervals.

N100 cortical potentials accompanying disrupted auditory nerve activity in auditory neuropathy (AN): effects of signal intensity and continuous noise.

Objective: Auditory temporal processes in quiet are impaired in auditory neuropathy (AN) similar to normal hearing subjects tested in noise. N100 latencies were measured from AN subjects at several tone intensities in quiet and noise for comparison with a group of normal hearing individuals.

Methods: Subjects were tested with brief 100 ms tones (1.

Intensity changes in a continuous tone: auditory cortical potentials comparison with frequency changes.

Objectives: To examine auditory cortical potentials in normal-hearing subjects to intensity increments in a continuous pure tone at low, mid, and high frequency.

Methods: Electrical scalp potentials were recorded in response to randomly occurring 100 ms intensity increments of continuous 250, 1000, and 4000 Hz tones every 1.4 s.

Auditory-evoked potentials to frequency increase and decrease of high- and low-frequency tones.

Objective: To define cortical brain responses to large and small frequency changes (increase and decrease) of high- and low-frequency tones.

Methods: Event-Related Potentials (ERPs) were recorded in response to a 10% or a 50% frequency increase from 250 or 4000 Hz tones that were approximately 3 s in duration and presented at 500-ms intervals. Frequency increase was followed after 1 s by a decrease back to base frequency.

ApoE genotype and abnormal auditory cortical potentials in healthy older females.

Apolipoprotein E (ApoE) status and gender are risk factors for the development of Alzheimer's disease. Alzheimer's disease is more prevalent in female relative to male carriers of the ApoE epsilon 4 gene. We examined cortical sensory (P50, N100) and cognitive (P300) potentials in an auditory target detection task in females as a function of ApoE genotype (ApoE epsilon 4 carriers, ApoE epsilon 4 non-carriers) to define the incidence of abnormalities prior to the clinical expression of cognitive impairments.

Frequency changes in a continuous tone: auditory cortical potentials.

Objective: We examined auditory cortical potentials in normal hearing subjects to spectral changes in continuous low and high frequency pure tones.

Methods: Cortical potentials were recorded to increments of frequency from continuous 250 or 4000Hz tones. The magnitude of change was random and varied from 0% to 50% above the base frequency.