title: Auditory Brainstem Response Latency in Noise as a Marker of Cochlear Synaptopathy.
abstract: Evidence from animal and human studies suggests that moderate acoustic exposure, causing only transient threshold elevation, can nonetheless cause "hidden hearing loss" that interferes with coding of suprathreshold sound. Such noise exposure destroys synaptic connections between cochlear hair cells and auditory nerve fibers; however, there is no clinical test of this synaptopathy in humans. In animals, synaptopathy reduces the amplitude of auditory brainstem response (ABR) wave-I. Unfortunately, ABR wave-I is difficult to measure in humans, limiting its clinical use. Here, using analogous measurements in humans and mice, we show that the effect of masking noise on the latency of the more robust ABR wave-V mirrors changes in ABR wave-I amplitude. Furthermore, in our human cohort, the effect of noise on wave-V latency predicts perceptual temporal sensitivity. Our results suggest that measures of the effects of noise on ABR wave-V latency can be used to diagnose cochlear synaptopathy in humans.
  
  
  CONCLUSIONS
  Although there are suspicions that cochlear synaptopathy affects humans with normal hearing thresholds, no one has yet reported a clinical measure that is a reliable marker of such loss. By combining human and animal data, we demonstrate that the latency of auditory brainstem response wave-V in noise reflects auditory nerve loss. This is the first study of human listeners with normal hearing thresholds that links individual differences observed in behavior and auditory brainstem response timing to cochlear synaptopathy. These results can guide development of a clinical test to reveal this previously unknown form of noise-induced hearing loss in humans.
authors.affiliation: Program in Speech and Hearing Bioscience and Technology, Harvard University/Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, Center for Computational Neuroscience and Neural Technology, Boston University, Boston, Massachusetts 02215, gmehraei@mit.edu.
authors.forename: Golbarg
authors.identifier: http://orcid.org/0000-0002-0389-8632
authors.initials: G
authors.lastname: Mehraei
authors.affiliation: Program in Speech and Hearing Bioscience and Technology, Harvard University/Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114.
authors.forename: Ann E
authors.identifier: http://orcid.org/0000-0003-1033-9887
authors.initials: AE
authors.lastname: Hickox
authors.affiliation: Center for Computational Neuroscience and Neural Technology, Boston University, Boston, Massachusetts 02215, Martinos Center for Biomedical Imaging, Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129.
authors.forename: Hari M
authors.identifier: http://orcid.org/0000-0001-8685-9630
authors.initials: HM
authors.lastname: Bharadwaj
authors.affiliation: Program in Speech and Hearing Bioscience and Technology, Harvard University/Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors.forename: Hannah
authors.initials: H
authors.lastname: Goldberg
authors.affiliation: Center for Computational Neuroscience and Neural Technology, Boston University, Boston, Massachusetts 02215, Cluster of Excellence Hearing4All and Medical Physics, Department of Medical Physics and Acoustics, Oldenburg University, 26129 Oldenburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Verhulst
authors.affiliation: Program in Speech and Hearing Bioscience and Technology, Harvard University/Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
authors.affiliation: Center for Computational Neuroscience and Neural Technology, Boston University, Boston, Massachusetts 02215, Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215.
authors.forename: Barbara G
authors.identifier: http://orcid.org/0000-0002-5096-5914
authors.initials: BG
authors.lastname: Shinn-Cunningham
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000818:Animals; D001307:Auditory Perception / Q000502:physiology; D001309:Auditory Threshold / Q000502:physiology; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000473:pathology*; D004569:Electroencephalography; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D005260:Female; D006317:Hearing Loss, Noise-Induced / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D009622:Noise; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D011930:Reaction Time / Q000502:physiology*; D013569:Synapses / Q000473:pathology*; D055815:Young Adult
keywords: auditory brainstem response; auditory nerve loss; cochlear synaptopathy; hidden hearing loss; temporal coding