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      Resting-state network dysfunction in Alzheimer's disease: A systematic review and meta-analysis

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          Abstract

          Introduction

          We performed a systematic review and meta-analysis of the Alzheimer's disease (AD) literature to examine consistency of functional connectivity alterations in AD dementia and mild cognitive impairment, using resting-state functional magnetic resonance imaging.

          Methods

          Studies were screened using a standardized procedure. Multiresolution statistics were performed to assess the spatial consistency of findings across studies.

          Results

          Thirty-four studies were included (1363 participants, average 40 per study). Consistent alterations in connectivity were found in the default mode, salience, and limbic networks in patients with AD dementia, mild cognitive impairment, or in both groups. We also identified a strong tendency in the literature toward specific examination of the default mode network.

          Discussion

          Convergent evidence across the literature supports the use of resting-state connectivity as a biomarker of AD. The locations of consistent alterations suggest that highly connected hub regions in the brain might be an early target of AD.

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          Most cited references71

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

          Yoav Benjamini, Yosef Hochberg (1995)
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            Selective changes of resting-state networks in individuals at risk for Alzheimer's disease.

            Christian Sorg, Valentin Riedl, Mark Mühlau … (2007)
            Alzheimer's disease (AD) is a neurodegenerative disorder that prominently affects cerebral connectivity. Assessing the functional connectivity at rest, recent functional MRI (fMRI) studies reported on the existence of resting-state networks (RSNs). RSNs are characterized by spatially coherent, spontaneous fluctuations in the blood oxygen level-dependent signal and are made up of regional patterns commonly involved in functions such as sensory, attention, or default mode processing. In AD, the default mode network (DMN) is affected by reduced functional connectivity and atrophy. In this work, we analyzed functional and structural MRI data from healthy elderly (n = 16) and patients with amnestic mild cognitive impairment (aMCI) (n = 24), a syndrome of high risk for developing AD. Two questions were addressed: (i) Are any RSNs altered in aMCI? (ii) Do changes in functional connectivity relate to possible structural changes? Independent component analysis of resting-state fMRI data identified eight spatially consistent RSNs. Only selected areas of the DMN and the executive attention network demonstrated reduced network-related activity in the patient group. Voxel-based morphometry revealed atrophy in both medial temporal lobes (MTL) of the patients. The functional connectivity between both hippocampi in the MTLs and the posterior cingulate of the DMN was present in healthy controls but absent in patients. We conclude that in individuals at risk for AD, a specific subset of RSNs is altered, likely representing effects of ongoing early neurodegeneration. We interpret our finding as a proof of principle, demonstrating that functional brain disorders can be characterized by functional-disconnectivity profiles of RSNs.
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              Growing together and growing apart: regional and sex differences in the lifespan developmental trajectories of functional homotopy.

              Xi-Nian Zuo, Clare Kelly, Adriana Di Martino … (2010)
              Functional homotopy, the high degree of synchrony in spontaneous activity between geometrically corresponding interhemispheric (i.e., homotopic) regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, despite its prominence, the lifespan development of the homotopic resting-state functional connectivity (RSFC) of the human brain is rarely directly examined in functional magnetic resonance imaging studies. Here, we systematically investigated age-related changes in homotopic RSFC in 214 healthy individuals ranging in age from 7 to 85 years. We observed marked age-related changes in homotopic RSFC with regionally specific developmental trajectories of varying levels of complexity. Sensorimotor regions tended to show increasing homotopic RSFC, whereas higher-order processing regions showed decreasing connectivity (i.e., increasing segregation) with age. More complex maturational curves were also detected, with regions such as the insula and lingual gyrus exhibiting quadratic trajectories and the superior frontal gyrus and putamen exhibiting cubic trajectories. Sex-related differences in the developmental trajectory of functional homotopy were detected within dorsolateral prefrontal cortex (Brodmann areas 9 and 46) and amygdala. Evidence of robust developmental effects in homotopic RSFC across the lifespan should serve to motivate studies of the physiological mechanisms underlying functional homotopy in neurodegenerative and psychiatric disorders.
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                Author and article information

                Contributors
                AmanPreet Badhwar
                Pierre Bellec
                Journal
                Journal ID (nlm-ta): Alzheimers Dement (Amst)
                Journal ID (iso-abbrev): Alzheimers Dement (Amst)
                Title: Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring
                Publisher: Elsevier
                ISSN (Electronic): 2352-8729
                Publication date PMC-release: 18 April 2017
                Publication date Collection: 2017
                Publication date (Electronic): 18 April 2017
                Volume: 8
                Pages: 73-85
                Affiliations
                [a ]Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Montreal, Quebec, Canada
                [b ]Université de Montréal, Montreal, Quebec, Canada
                [c ]McGill University, Montreal, Quebec, Canada
                [d ]Douglas Mental Health University Institute Research Centre, Montreal, Quebec, Canada
                [e ]Institute of Neuroscience and Medicine (INM-1, INM-7), Research Centre Jülich, Jülich, Germany
                [f ]Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
                [g ]Institute of Systems Neuroscience, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
                Author notes
                [∗ ]Corresponding author. Tel.: +1-514-340-3540x3367; Fax: +1-514-340-2802. amanpreet.badhwar@ 123456criugm.qc.ca
                [∗∗ ]Corresponding author. Tel.: +1-514-340-3540x4782; Fax: +1-514-340-2802. pierre.bellec@ 123456criugm.qc.ca
                Article
                Publisher ID: S2352-8729(17)30022-2
                DOI: 10.1016/j.dadm.2017.03.007
                PMC ID: 5436069
                PubMed ID: 28560308
                SO-VID: 8b5fe45f-480a-43d8-b278-6e9656106127
                Copyright © © 2017 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Subject: Neuroimaging

                Keywords: resting-state fmri,functional connectivity,alzheimer's disease,mild cognitive impairment,meta-analysis
                Data availability:
                Keywords: resting-state fmri, functional connectivity, alzheimer's disease, mild cognitive impairment, meta-analysis

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