A Revised Surgical Approach to Induce Endolymphatic Hydrops in the Guinea Pig

Endolymphatic hydrops is an enlargement of scala media that is most often associated with Meniere&#39;s disease, though the pathophysiologic mechanism(s) ...

Washington University School of Medicine in St. Louis

Autism spectrum disorder (ASD) is a developmental disability that is poorly understood. ASD can influence communication, social interaction, and behavior. Children with ASD often have sensory hypersensitivities, including auditory hypersensitivity (hyperacusis). In adults with hyperacusis who are otherwise neurotypical, the medial olivocochlear (MOC) efferent reflex is stronger than usual. In children with ASD, the MOC reflex has been measured, but without also assessing hyperacusis. We assessed the MOC reflex in children with ASD by measuring the strength of MOC-induced inhibition of transient-evoked otoacoustic emissions (TEOAEs), a noninvasive physiological measure that reflects cochlear amplification. MOC activity was evoked by contralateral noise. Hyperacusis was assessed subjectively on the basis of the children's symptoms. We found a significant correlation between hyperacusis scores and MOC strength in children with ASD. When children were divided into ASD-with-severe-hyperacusis (ASDs), ASD-with-not-severe-hyperacusis (ASDns), and neurotypical (NT) groups, the last two groups had similar hyperacusis and MOC reflexes, whereas the ASDs group, on average, had hyperacusis and MOC reflexes that were approximately twice as strong. The MOC inhibition of TEOAEs averaged larger at all frequencies in the ASDs compared with ASDns and NT groups. The results suggest that the MOC reflex can be used to estimate hyperacusis in children with ASD and might be used to validate future questionnaires to assess hyperacusis. Our results also provide evidence that strong MOC reflexes in children with ASD are associated with hyperacusis and that hyperacusis is a comorbid condition and is not a necessary, integral part of the abnormal neural processing associated with ASD. Children with autism spectrum disorder (ASD) are a heterogeneous group, some with hyperacusis and some without. Our research shows that hyperacusis can be estimated in children with ASD by using medial olivocochlear (MOC) reflex measurements. By establishing that an objective measure correlates with attributes of hyperacusis, our results enable future work to enable subtyping of children with ASD to provide improved individualized treatments to at-risk children and those without adequate language to describe their hyperacusis symptoms.

Efferent inhibition strength is a physiological correlate of hyperacusis in children with autism spectrum disorder.

Endolymphatic hydrops is associated with low-frequency sensorineural hearing loss, with a large body of research dedicated to examining its putative causal role in low-frequency hearing loss. Investigations have been thwarted by the fact that hearing loss is measured in intact ears, but gold standard assessments of endolymphatic hydrops are made postmortem only; and that no objective low-frequency hearing measure has existed. Yet the association of endolymphatic hydrops with low-frequency hearing loss is so strong that it has been established as one of the important defining features for Ménière's disease, rendering it critical to detect endolymphatic hydrops early, regardless of whether it serves a causal role or is the result of other disease mechanisms. We surgically induced endolymphatic hydrops in guinea pigs and employed our recently developed objective neural measure of low-frequency hearing, the Auditory Nerve Overlapped Waveform (ANOW). Hearing loss and endolymphatic hydrops were assessed at various time points after surgery. The ANOW detected low-frequency hearing loss as early as the first day after surgery, well before endolymphatic hydrops was found histologically. The ANOW detected low-frequency hearing loss with perfect sensitivity and specificity in all ears after endolymphatic hydrops developed, where there was a strong linear relationship between degree of endolymphatic hydrops and severity of low-frequency hearing loss. Further, histological data demonstrated that endolymphatic hydrops is seen first in the high-frequency cochlear base, though the ANOW demonstrated that dysfunction begins in the low-frequency apical cochlear half. The results lay the groundwork for future investigations of the causal role of endolymphatic hydrops in low-frequency hearing loss.

Early Detection of Endolymphatic Hydrops using the Auditory Nerve Overlapped Waveform (ANOW).

Cochlear amplification of basilar membrane traveling waves is thought to occur between a tone's characteristic frequency (CF) place and within one octave basal of the CF. Evidence for this view comes only from the cochlear base. Stimulus-frequency otoacoustic emissions (SFOAEs) provide a noninvasive alternative to direct measurements of cochlear motion that can be measured across a wide range of CF regions. Coherent reflection theory indicates that SFOAEs arise mostly from the peak region of the traveling wave, but several studies using far-basal suppressor tones claimed that SFOAE components originate many octaves basal of CF. We measured SFOAEs while perfusing guinea pig cochleas from apex to base with salicylate or KCl solutions that reduced outer-hair-cell function and SFOAE amplification. Solution effects on inner hair cells reduced auditory nerve compound action potentials (CAPs) and provided reference times for when solutions reached the SFOAE-frequency CF region. As solution flowed from apex to base, SFOAE reductions generally occurred later than CAP reductions and showed that the effects of cochlear amplification usually peaked ∼1/2 octave basal of the CF region. For tones ≥2 kHz, cochlear amplification typically extended ∼1.5 octaves basal of CF, and the data are consistent with coherent reflection theory. SFOAE amplification did not extend to the basal end of the cochlea, even though reticular lamina motion is amplified in this region, which indicates that reticular lamina motion is not directly coupled to basilar membrane traveling waves. Previous reports of SFOAE-frequency residuals produced by suppressor frequencies far above the SFOAE frequency are most likely due to additional sources created by the suppressor. For some tones <2 kHz, SFOAE amplification extended two octaves apical of CF, which highlights that different vibratory motions produce SFOAEs and CAPs, and that the amplification region depends on the cochlear mode of motion considered. The concept that there is a single "cochlear amplification region" needs to be revised.

Jeffery T. Lichtenhan

Department of Otolaryngology,
Head and Neck Surgery,
Department of Otolaryngology, Head and Neck Surgery

Washington University School of Medicine in St. Louis

A Revised Surgical Approach to Induce Endolymphatic Hydrops in the Guinea Pig

Jeffery T. Lichtenhan

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Otolaryngology,Head and Neck Surgery,Department of Otolaryngology, Head and Neck Surgery

Washington University School of Medicine in St. Louis

A Revised Surgical Approach to Induce Endolymphatic Hydrops in the Guinea Pig

Department of Otolaryngology,
Head and Neck Surgery,
Department of Otolaryngology, Head and Neck Surgery