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The brainstem nucleus locus coeruleus (LC) is a promising target for early diagnosis because of its early structural alterations and its relationship to the functional disturbances in the patients. In this study, we applied our improved method of localisation\u2010based LC resting\u2010state fMRI to investigate the differences in central sensory signal processing when comparing functional connectivity (fc) of a patient group with mild cognitive impairment (MCI, <jats:italic>n<\/jats:italic>\u00a0=\u00a028) and an age\u2010matched healthy control group (<jats:italic>n<\/jats:italic>\u00a0=\u00a029). MCI and control participants could be differentiated in their Mini\u2010Mental\u2010State\u2010Examination (MMSE) scores (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and LC intensity ratio (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.010). In the fMRI, LC fc to anterior cingulate cortex (FDR <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and left anterior insula (FDR <jats:italic>p<\/jats:italic>\u00a0=\u00a0.012) was elevated, and LC fc to right temporoparietal junction (rTPJ, FDR <jats:italic>p<\/jats:italic>\u00a0=\u00a0.012) and posterior cingulate cortex (PCC, FDR <jats:italic>p<\/jats:italic>\u00a0=\u00a0.021) was decreased in the patient group. Importantly, LC to rTPJ connectivity was also positively correlated to MMSE scores in MCI patients (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.017). Furthermore, we found a hyperactivation of the left\u2010insula salience network in the MCI patients. Our results and our proposed disease model shed new light on the functional pathogenesis of MCI by directing to attentional network disturbances, which could aid new therapeutic strategies and provide a marker for diagnosis and prediction of disease progression.<\/jats:p>","DOI":"10.1002\/hbm.26039","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T09:45:35Z","timestamp":1660211135000},"page":"5630-5642","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Investigation of the functional pathogenesis of mild cognitive impairment by localisation\u2010based locus coeruleus resting\u2010state <scp>fMRI<\/scp>"],"prefix":"10.1002","volume":"43","author":[{"given":"Thomas","family":"Liebe","sequence":"first","affiliation":[{"name":"Department of Psychiatry Medical University of Vienna  Vienna Austria"},{"name":"Department of Radiology University Hospital Jena  Jena 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