title: Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network.
abstract: Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed.
authors.affiliation: Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Physiology, Southeast University, Nanjing, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology, Southeast University, Nanjing, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Physiology, Southeast University, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Chun-Qiang
authors.initials: CQ
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Feng-Chao
authors.initials: FC
authors.lastname: Zang
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, The State University of New York, Buffalo, United States.
authors.forename: Kelly
authors.initials: K
authors.lastname: Radziwon
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, The State University of New York, Buffalo, United States.
authors.forename: Guang-Di
authors.initials: GD
authors.lastname: Chen
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, The State University of New York, Buffalo, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, The State University of New York, Buffalo, United States.
authors.forename: Vijaya Prakash
authors.initials: VP
authors.lastname: Krishnan Muthaiah
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, The State University of New York, Buffalo, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
authors.affiliation: Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Gao-Jun
authors.initials: GJ
authors.lastname: Teng
mesh_terms: D000679:Amygdala / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001303:Auditory Cortex / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology*; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005829:Geniculate Bodies / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D012001:Hyperacusis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007245:Inferior Colliculi / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008960:Models, Psychological; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D011595:Psychomotor Agitation / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000473:pathology / Q000503:physiopathology*; D020156:Salicylic Acid; D014012:Tinnitus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
chemical_list: D020156:Salicylic Acid
keywords: ALFF; functional MRI; functional connectivity; hyperacusis; neuroscience; rat; salicylate; tinnitus