title: The middle ear muscle reflex in the diagnosis of cochlear neuropathy.
abstract: Cochlear neuropathy, i.e. the loss of auditory nerve fibers (ANFs) without loss of hair cells, may cause hearing deficits without affecting threshold sensitivity, particularly if the subset of ANFs with high thresholds and low spontaneous rates (SRs) is preferentially lost, as appears to be the case in both aging and noise-damaged cochleas. Because low-SR fibers may also be important drivers of the medial olivocochlear reflex (MOCR) and middle-ear muscle reflex (MEMR), these reflexes might be sensitive metrics of cochlear neuropathy. To test this hypothesis, we measured reflex strength and reflex threshold in mice with noise-induced neuropathy, as documented by confocal analysis of immunostained cochlear whole-mounts. To assay the MOCR, we measured contra-noise modulation of ipsilateral distortion-product otoacoustic emissions (DPOAEs) before and after the administration of curare to block the MEMR or curare + strychnine to also block the MOCR. The modulation of DPOAEs was 1) dominated by the MEMR in anesthetized mice, with a smaller contribution from the MOCR, and 2) significantly attenuated in neuropathic mice, but only when the MEMR was intact. We then measured MEMR growth functions by monitoring contra-noise induced changes in the wideband reflectance of chirps presented to the ipsilateral ear. We found 1) that the changes in wideband reflectance were mediated by the MEMR alone, and 2) that MEMR threshold was elevated and its maximum amplitude was attenuated in neuropathic mice. These data suggest that the MEMR may be valuable in the early detection of cochlear neuropathy.
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: Michelle_Valero@meei.harvard.edu.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Valero
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Hancock
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001299:Audiometry; D001305:Auditory Fatigue; D001309:Auditory Threshold; D003056:Cochlear Nerve / Q000187:drug effects / Q000503:physiopathology*; D003472:Curare / Q000008:administration & dosage; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000294:innervation*; D042241:Early Diagnosis; D006317:Hearing Loss, Noise-Induced / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008808:Mice, Inbred CBA; D018482:Muscle, Skeletal / Q000294:innervation*; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage; D009622:Noise / Q000009:adverse effects; D017084:Otoacoustic Emissions, Spontaneous; D011237:Predictive Value of Tests; D012018:Reflex / Q000187:drug effects; D013331:Strychnine / Q000008:administration & dosage; D009435:Synaptic Transmission; D000160:Vestibulocochlear Nerve Diseases / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology
chemical_list: D003473:Neuromuscular Nondepolarizing Agents; D003472:Curare; D013331:Strychnine
keywords: Acoustic overexposure; Cochlear neuropathy; Hidden hearing loss; Medial olivocochlear reflex; Middle-ear muscle reflex; Wideband reflectance