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Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole\u2010brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate\u2010induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high\u2010gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.<\/jats:p>","DOI":"10.1002\/advs.202304709","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T19:09:37Z","timestamp":1701112177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-7803","authenticated-orcid":false,"given":"Ting","family":"Fan","sequence":"first","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology EYE &amp; ENT Hospital Fudan University  Shanghai 200031 China"},{"name":"NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng\u2010Fei","family":"Guan","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology EYE &amp; 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