title: Tinnitus and hyperacusis: Contributions of paraflocculus, reticular formation and stress.
abstract: Tinnitus and hyperacusis are common and potentially serious hearing disorders associated with noise-, age- or drug-induced hearing loss. Accumulating evidence suggests that tinnitus and hyperacusis are linked to excessive neural activity in a distributed brain network that not only includes the central auditory pathway, but also brain regions involved in arousal, emotion, stress and motor control. Here we examine electrophysiological changes in two novel non-auditory areas implicated in tinnitus and hyperacusis: the caudal pontine reticular nucleus (PnC), involved in arousal, and the paraflocculus lobe of the cerebellum (PFL), implicated in head-eye coordination and gating tinnitus and we measure the changes in corticosterone stress hormone levels. Using the salicylate-induced model of tinnitus and hyperacusis, we found that long-latency (>10 ms) sound-evoked response components in both the brain regions were significantly enhanced after salicylate administration, while the short-latency responses were reduced, likely reflecting cochlear hearing loss. These results are consistent with the central gain model of tinnitus and hyperacusis, which proposes that these disorders arise from the amplification of neural activity in central auditory pathway plus other regions linked to arousal, emotion, tinnitus gating and motor control. Finally, we demonstrate that salicylate results in an increase in corticosterone level in a dose-dependent manner consistent with the notion that stress may interact with hearing loss in tinnitus and hyperacusis development. This increased stress response has the potential to have wide-ranging effects on the central nervous system and may therefore contribute to brain-wide changes in neural activity.
authors.affiliation: Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, China; Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, NY 14214, USA. Electronic address: gchen7@buffalo.edu.
authors.forename: Guang-Di
authors.initials: GD
authors.lastname: Chen
authors.affiliation: Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Auerbach
authors.affiliation: Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Senthilvelan
authors.initials: S
authors.lastname: Manohar
authors.affiliation: Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Radziwon
authors.affiliation: Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001306:Auditory Pathways / Q000503:physiopathology; D001522:Behavior, Animal; D015415:Biomarkers / Q000097:blood; D002531:Cerebellum / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004644:Emotions; D005072:Evoked Potentials, Auditory; D006309:Hearing; D012001:Hyperacusis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D066265:Midbrain Reticular Formation / Q000503:physiopathology*; D009043:Motor Activity; D065821:Pontine Tegmentum / Q000473:pathology / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012980:Sodium Salicylate; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology* / Q000523:psychology; D013997:Time Factors; D014012:Tinnitus / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology
chemical_list: D015415:Biomarkers; D003345:Corticosterone; D012980:Sodium Salicylate
keywords: Corticosterone; Hyperacusis; Paraflocculus; Reticular formation; Salicylate; Stress; Tinnitus