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      Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test


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          Idiopathic Normal Pressure Hydrocephalus (iNPH)—the leading cause of reversible dementia in aging—is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH‐specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer's disease (AD). Here we investigate the resting‐state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer's pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive‐control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD‐pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross‐network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.


          Idiopathic normal pressure hydrocephalus (iNPH), the leading cause of reversible dementia in ageing, is a prevalent neurological disorder characterised by gait, urinary, and cognitive impairments with ventriculomegaly. We show that iNPH patients have changes of brain functional dynamics which explain gait and executive deficits, are partially reverted by a CSF tap test, and are not driven by Alzheimer's disease or cerebrovascular comorbidities. Our results shed new light on the neurobiological substrates of iNPH and functional plasticity mechanisms following an invasive intervention, with possible implications for iNPH differential diagnosis and better clinical management.

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              The organization of the human cerebral cortex estimated by intrinsic functional connectivity.

              Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

                Author and article information

                Hum Brain Mapp
                Hum Brain Mapp
                Human Brain Mapping
                John Wiley & Sons, Inc. (Hoboken, USA )
                09 December 2020
                1 April 2021
                : 42
                : 5 ( doiID: 10.1002/hbm.v42.5 )
                : 1485-1502
                [ 1 ] Department of Clinical Neurosciences, Division of Neurology Geneva University Hospitals and Faculty of Medicine, University of Geneva Geneva Switzerland
                [ 2 ] Institute of Bioengineering Center of Neuroprosthetics, École Polytechnique Fédérale De Lausanne (EPFL) Geneva Switzerland
                [ 3 ] Department of Rehabilitation and Geriatrics Geneva University Hospitals and University of Geneva Geneva Switzerland
                [ 4 ] Department of Radiology and Medical Informatics University of Geneva Geneva Switzerland
                [ 5 ] Department of Neurology, Division of Cognitive & Motor Aging Albert Einstein College of Medicine, Yeshiva University Bronx New York USA
                Author notes
                [*] [* ] Correspondence

                Alessandra Griffa, Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.

                Email: alessandra.griffa@ 123456gmail.com

                Author information
                © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                : 13 August 2020
                : 02 November 2020
                : 26 November 2020
                Page count
                Figures: 6, Tables: 2, Pages: 18, Words: 16585
                Funded by: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung , open-funder-registry 10.13039/501100001711;
                Award ID: 320030_173153
                Funded by: Swiss National Science Foundation , open-funder-registry 10.13039/501100001711;
                Research Article
                Research Articles
                Custom metadata
                April 1, 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.9 mode:remove_FC converted:03.03.2021

                brain dynamics,brain plasticity,co‐activation pattern analysis,csf tap test,default mode network,normal pressure hydrocephalus,resting state fmri


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