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Title: The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease.
Austin Authors: Khan, Wasim;Amad, Ali;Giampietro, Vincent;Werden, Emilio ;De Simoni, Sara;O'Muircheartaigh, Jonathan;Westman, Eric;O'Daly, Owen;Williams, Steve C R;Brodtmann, Amy 
Affiliation: Eastern Clinical Research Unit, Monash University, Box Hill Hospital, Melbourne, Victoria, Australia
MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK
Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London, UK
Department of Perinatal Imaging and Health, St. Thomas' Hospital, King's College London, London, UK
Univ Lille Nord de France, CHRU de Lille, Lille, France
The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia
Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London, UK
Austin Health, Heidelberg, Victoria, Australia
NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK
NIHR Biomedical Research Unit for Dementia, King's College London, London, UK
Computational, Cognitive and Clinical Neuroimaging Laboratory, Imperial College London, Division of Brain Sciences, Hammersmith Hospital, London, UK
Issue Date: 15-Apr-2020 2019-12-19
Publication information: Human Brain Mapping 2020; 41(6): 1557-1572
Abstract: The posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimer's disease (AD). 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-based subdivisions in the PMC to AD pathogenesis. Using a data-driven 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-brain 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.
DOI: 10.1002/hbm.24894
ORCID: 0000-0002-4489-4945
Journal: Human Brain Mapping
PubMed URL: 31854490
Type: Journal Article
Subjects: Alzheimer disease
magnetic resonance imaging
multivariate analysis
posterior cingulate cortex
Appears in Collections:Journal articles

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