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      Dynamic functional network reconfiguration underlying the pathophysiology of schizophrenia and autism spectrum disorder

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          Abstract

          The dynamics of the human brain span multiple spatial scales, from connectivity associated with a specific region/network to the global organization, each representing different brain mechanisms. Yet brain reconfigurations at different spatial scales are seldom explored and whether they are associated with the neural aspects of brain disorders is far from understood. In this study, we introduced a dynamic measure called step‐wise functional network reconfiguration (sFNR) to characterize how brain configuration rewires at different spatial scales. We applied sFNR to two independent datasets, one includes 160 healthy controls (HCs) and 151 patients with schizophrenia (SZ) and the other one includes 314 HCs and 255 individuals with autism spectrum disorder (ASD). We found that both SZ and ASD have increased whole‐brain sFNR and sFNR between cerebellar and subcortical/sensorimotor domains. At the ICN level, the abnormalities in SZ are mainly located in ICNs within subcortical, sensory, and cerebellar domains, while the abnormalities in ASD are more widespread across domains. Interestingly, the overlap SZ‐ASD abnormality in sFNR between cerebellar and sensorimotor domains was correlated with the reasoning‐problem‐solving performance in SZ ( r = −.1652, p = .0058) as well as the Autism Diagnostic Observation Schedule in ASD ( r = .1853, p = .0077). Our findings suggest that dynamic reconfiguration deficits may represent a key intersecting point for SZ and ASD. The investigation of brain dynamics at different spatial scales can provide comprehensive insights into the functional reconfiguration, which might advance our knowledge of cognitive decline and other pathophysiology in brain disorders.

          Abstract

          In this study, we found that both schizophrenia and autism have increased whole‐brain dynamic network reconfiguration and increased dynamic network reconfiguration associated with cerebellar and subcortical/sensorimotor domains. Interestingly, the diseases' overlapping abnormality in dynamic network reconfiguration between cerebellar and sensorimotor domains was correlated with the reasoning‐problem‐solving performance in schizophrenia as well as the Autism Diagnostic Observation Schedule in autism. Our findings suggest that dynamic functional connectivity deficits may represent a key intersecting point for schizophrenia and autism.

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

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            Sparse inverse covariance estimation with the graphical lasso.

            We consider the problem of estimating sparse graphs by a lasso penalty applied to the inverse covariance matrix. Using a coordinate descent procedure for the lasso, we develop a simple algorithm--the graphical lasso--that is remarkably fast: It solves a 1000-node problem ( approximately 500,000 parameters) in at most a minute and is 30-4000 times faster than competing methods. It also provides a conceptual link between the exact problem and the approximation suggested by Meinshausen and Bühlmann (2006). We illustrate the method on some cell-signaling data from proteomics.
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              Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.

              An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10(-3)) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.
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                Author and article information

                Contributors
                fzn198637@gmail.com
                Journal
                Hum Brain Mapp
                Hum Brain Mapp
                10.1002/(ISSN)1097-0193
                HBM
                Human Brain Mapping
                John Wiley & Sons, Inc. (Hoboken, USA )
                1065-9471
                1097-0193
                23 September 2020
                January 2021
                : 42
                : 1 ( doiID: 10.1002/hbm.v42.1 )
                : 80-94
                Affiliations
                [ 1 ] Tri‐Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) Georgia State University, Georgia Institute of Technology, Emory University Atlanta Georgia USA
                [ 2 ] Chinese Academy of Sciences (CAS) Centre for Excellence in Brain Science and Intelligence Technology University of Chinese Academy of Sciences Beijing China
                [ 3 ] Department of Psychology Georgia State University Atlanta Georgia USA
                [ 4 ] School of Computer and Information Technology Shanxi University Taiyuan China
                [ 5 ] Olin Neuropsychiatry Research Center, The Institute of Living Hartford Connecticut USA
                [ 6 ] Department of Psychiatry Yale University School of Medicine New Haven Connecticut USA
                Author notes
                [*] [* ] Correspondence

                Zening Fu, Tri‐Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA.

                Email: fzn198637@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-1591-4900
                https://orcid.org/0000-0001-6837-5966
                https://orcid.org/0000-0002-0079-8177
                Article
                HBM25205
                10.1002/hbm.25205
                7721229
                32965740
                352286d1-159d-47fa-9074-e674b89f0c2b
                © 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.

                History
                : 27 April 2020
                : 14 July 2020
                : 05 September 2020
                Page count
                Figures: 5, Tables: 1, Pages: 15, Words: 11292
                Funding
                Funded by: National Institutes of Health (NIH) , open-funder-registry 10.13039/100000002;
                Award ID: R37MH43775
                Award ID: P20GM103472
                Award ID: R01REB020407
                Award ID: R01EB006841
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                January 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.5 mode:remove_FC converted:07.12.2020

                Neurology
                autism spectrum disorder,dynamic functional connectivity,network reconfiguration at different spatial scales,schizophrenia

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