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      Reconceptualizing functional brain connectivity in autism from a developmental perspective

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          Abstract

          While there is almost universal agreement amongst researchers that autism is associated with alterations in brain connectivity, the precise nature of these alterations continues to be debated. Theoretical and empirical work is beginning to reveal that autism is associated with a complex functional phenotype characterized by both hypo- and hyper-connectivity of large-scale brain systems. It is not yet understood why such conflicting patterns of brain connectivity are observed across different studies, and the factors contributing to these heterogeneous findings have not been identified. Developmental changes in functional connectivity have received inadequate attention to date. We propose that discrepancies between findings of autism related hypo-connectivity and hyper-connectivity might be reconciled by taking developmental changes into account. We review neuroimaging studies of autism, with an emphasis on functional magnetic resonance imaging studies of intrinsic functional connectivity in children, adolescents and adults. The consistent pattern emerging across several studies is that while intrinsic functional connectivity in adolescents and adults with autism is generally reduced compared with age-matched controls, functional connectivity in younger children with the disorder appears to be increased. We suggest that by placing recent empirical findings within a developmental framework, and explicitly characterizing age and pubertal stage in future work, it may be possible to resolve conflicting findings of hypo- and hyper-connectivity in the extant literature and arrive at a more comprehensive understanding of the neurobiology of autism.

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          Most cited references73

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          A self-report measure of pubertal status: Reliability, validity, and initial norms.

          Puberty is a central process in the complex set of changes that constitutes the transition from childhood to adolescence. Research on the role of pubertal change in this transition has been impeded by the difficulty of assessing puberty in ways acceptable to young adolescents and others involved. Addressing this problem, this paper describes and presents norms for a selfreport measure of pubertal status. The measure was used twice annually over a period of three years in a longitudinal study of 335 young adolescent boys and girls. Data on a longitudinal subsample of 253 subjects are reported. The scale shows good reliability, as indicated by coefficient alpha. In addition, several sources of data suggest that these reports are valid. The availability of such a measure is important for studies, such as those based in schools, in which more direct measures of puberty may not be possible.
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            An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data.

            Several recent reports in large, independent samples have demonstrated the influence of motion artifact on resting-state functional connectivity MRI (rsfc-MRI). Standard rsfc-MRI preprocessing typically includes regression of confounding signals and band-pass filtering. However, substantial heterogeneity exists in how these techniques are implemented across studies, and no prior study has examined the effect of differing approaches for the control of motion-induced artifacts. To better understand how in-scanner head motion affects rsfc-MRI data, we describe the spatial, temporal, and spectral characteristics of motion artifacts in a sample of 348 adolescents. Analyses utilize a novel approach for describing head motion on a voxelwise basis. Next, we systematically evaluate the efficacy of a range of confound regression and filtering techniques for the control of motion-induced artifacts. Results reveal that the effectiveness of preprocessing procedures on the control of motion is heterogeneous, and that improved preprocessing provides a substantial benefit beyond typical procedures. These results demonstrate that the effect of motion on rsfc-MRI can be substantially attenuated through improved preprocessing procedures, but not completely removed. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Autism spectrum disorders: developmental disconnection syndromes.

              Autism is a common and heterogeneous childhood neurodevelopmental disorder. Analogous to broad syndromes such as mental retardation, autism has many etiologies and should be considered not as a single disorder but, rather, as 'the autisms'. However, recent genetic findings, coupled with emerging anatomical and functional imaging studies, suggest a potential unifying model in which higher-order association areas of the brain that normally connect to the frontal lobe are partially disconnected during development. This concept of developmental disconnection can accommodate the specific neurobehavioral features that are observed in autism, their emergence during development, and the heterogeneity of autism etiology, behaviors and cognition.
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                Author and article information

                Journal
                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                1662-5161
                07 August 2013
                2013
                : 7
                : 458
                Affiliations
                [1] 1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine Stanford, CA, USA
                [2] 2Program in Neuroscience, Stanford University School of Medicine Stanford, CA, USA
                [3] 3Department of Neurology and Neurological Sciences, Stanford University School of Medicine Stanford, CA, USA
                Author notes

                Edited by: Rajesh K. Kana, University of Alabama at Birmingham, USA

                Reviewed by: Qingbao Yu, The Mind Research Network, USA; R. Matthew Hutchison, Western University, Canada; Timothy A. Keller, Carnegie Mellon University, USA; Diane L. Williams, Duquesne University, USA

                *Correspondence: Lucina Q. Uddin, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd., Stanford, CA 94305-5719, USA e-mail: lucina@ 123456stanford.edu
                Article
                10.3389/fnhum.2013.00458
                3735986
                23966925
                a2b0da6e-d979-4ea6-bb18-f907cdf905b1
                Copyright © 2013 Uddin, Supekar and Menon.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 April 2013
                : 22 July 2013
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 112, Pages: 11, Words: 9301
                Categories
                Neuroscience
                Review Article

                Neurosciences
                autism spectrum disorders,brain development,functional connectivity,puberty,fmri
                Neurosciences
                autism spectrum disorders, brain development, functional connectivity, puberty, fmri

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