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Previous studies have demonstrated a heterogenous functional architecture of the region that is composed of discrete functional modules reflecting a complex pattern of functional connectivity. However, little is understood about the mechanisms underpinning this complex network architecture in neurodegenerative disease, and the differential vulnerability of connectivity\u2010based subdivisions in the PMC to AD pathogenesis. Using a data\u2010driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project to characterise the local functional connectivity patterns within the PMC, and its unique whole\u2010brain functional connectivity. These distinct connectivity profiles were subsequently quantified in the Alzheimer's Disease Neuroimaging Initiative study, to examine functional connectivity differences in AD patients and cognitively normal (CN) participants, as well as the entire AD pathological spectrum. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex (PCC), and the central precuneus in AD patients compared to CN participants. Functional abnormalities in the dorsal PCC and central precuneus were also related to amyloid burden and volumetric hippocampal loss. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease severity and specific deficits in memory and executive function. These findings provide new evidence showing that the PMC is selectively impacted in AD, with prominent network failures of the dorsal PCC and central precuneus underpinning the neurodegenerative and cognitive dysfunctions associated with the disease.<\/jats:p>","DOI":"10.1002\/hbm.24894","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T06:36:20Z","timestamp":1576737380000},"page":"1557-1572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-4945","authenticated-orcid":false,"given":"Wasim","family":"Khan","sequence":"first","affiliation":[{"name":"The Florey Institute for Neuroscience and Mental Health University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-2910","authenticated-orcid":false,"given":"Ali","family":"Amad","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London  London UK"},{"name":"Univ Lille Nord de France, CHRU de Lille  Lille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Giampietro","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Werden","sequence":"additional","affiliation":[{"name":"The Florey Institute for Neuroscience and Mental Health University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"De Simoni","sequence":"additional","affiliation":[{"name":"Computational, Cognitive and Clinical Neuroimaging Laboratory Imperial College London, Division of Brain Sciences, Hammersmith Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-6959","authenticated-orcid":false,"given":"Jonathan","family":"O'Muircheartaigh","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London  London UK"},{"name":"Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London  London UK"},{"name":"Department of Perinatal Imaging and Health St. Thomas' Hospital, King's College London  London UK"},{"name":"MRC Centre for Neurodevelopmental Disorders King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Westman","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London  London UK"},{"name":"Department of Neurobiology Care Sciences and Society, Karolinska Institute  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen","family":"O'Daly","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve C. 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