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      Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder

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          Abstract

          Background

          Neuroimaging studies can shed light on the neurobiological underpinnings of autism spectrum disorders (ASD). Studies of the resting brain have shown both altered baseline metabolism from PET/SPECT and altered functional connectivity (FC) of intrinsic brain networks based on resting-state fMRI. To date, however, no study has investigated these two physiological parameters of resting brain function jointly, or explored the relationship between these measures and ASD symptom severity.

          Methods

          Here, we used pseudo-continuous arterial spin labeling with 3D background-suppressed GRASE to assess resting cerebral blood flow (CBF) and FC in 17 youth with ASD and 22 matched typically developing (TD) children.

          Results

          A pattern of altered resting perfusion was found in ASD versus TD children including frontotemporal hyperperfusion and hypoperfusion in the dorsal anterior cingulate cortex. We found increased local FC in the anterior module of the default mode network (DMN) accompanied by decreased CBF in the same area. In our cohort, both alterations were associated with greater social impairments as assessed with the Social Responsiveness Scale (SRS-total T scores). While FC was correlated with CBF in TD children, this association between FC and baseline perfusion was disrupted in children with ASD. Furthermore, there was reduced long-range FC between anterior and posterior modules of the DMN in children with ASD.

          Conclusion

          Taken together, the findings of this study – the first to jointly assess resting CBF and FC in ASD – highlight new avenues for identifying novel imaging markers of ASD symptomatology.

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          Most cited references71

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          Diagnostic and statistical manual of mental disorders.

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            Rich-club organization of the human connectome.

            The human brain is a complex network of interlinked regions. Recent studies have demonstrated the existence of a number of highly connected and highly central neocortical hub regions, regions that play a key role in global information integration between different parts of the network. The potential functional importance of these "brain hubs" is underscored by recent studies showing that disturbances of their structural and functional connectivity profile are linked to neuropathology. This study aims to map out both the subcortical and neocortical hubs of the brain and examine their mutual relationship, particularly their structural linkages. Here, we demonstrate that brain hubs form a so-called "rich club," characterized by a tendency for high-degree nodes to be more densely connected among themselves than nodes of a lower degree, providing important information on the higher-level topology of the brain network. Whole-brain structural networks of 21 subjects were reconstructed using diffusion tensor imaging data. Examining the connectivity profile of these networks revealed a group of 12 strongly interconnected bihemispheric hub regions, comprising the precuneus, superior frontal and superior parietal cortex, as well as the subcortical hippocampus, putamen, and thalamus. Importantly, these hub regions were found to be more densely interconnected than would be expected based solely on their degree, together forming a rich club. We discuss the potential functional implications of the rich-club organization of the human connectome, particularly in light of its role in information integration and in conferring robustness to its structural core.
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              Model of autism: increased ratio of excitation/inhibition in key neural systems.

              Autism is a severe neurobehavioral syndrome, arising largely as an inherited disorder, which can arise from several diseases. Despite recent advances in identifying some genes that can cause autism, its underlying neurological mechanisms are uncertain. Autism is best conceptualized by considering the neural systems that may be defective in autistic individuals. Recent advances in understanding neural systems that process sensory information, various types of memories and social and emotional behaviors are reviewed and compared with known abnormalities in autism. Then, specific genetic abnormalities that are linked with autism are examined. Synthesis of this information leads to a model that postulates that some forms of autism are caused by an increased ratio of excitation/inhibition in sensory, mnemonic, social and emotional systems. The model further postulates that the increased ratio of excitation/inhibition can be caused by combinatorial effects of genetic and environmental variables that impinge upon a given neural system. Furthermore, the model suggests potential therapeutic interventions.
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                Author and article information

                Journal
                Brain Behav
                Brain Behav
                brb3
                Brain and Behavior
                John Wiley & Sons, Ltd (Chichester, UK )
                2162-3279
                2162-3279
                September 2015
                25 June 2015
                : 5
                : 9
                : e00358
                Affiliations
                [1 ]Laboratory of FMRI Technology (LOFT), Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, California
                [2 ]Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, California
                Author notes
                Correspondence Kay Jann, Laboratory of Functional MRI Technology, Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, 660 Charles E Young Drive South, Los Angeles, CA 90095. Tel: +1 310-206-2200; Fax: +1 310-794-7406; E-mail: kayjann@ 123456ucla.edu

                Funding Information This work was supported by grants from NICHD (P50 HD055784), NIMH (1R01- MH080892), 5P50HD055784-07 sub#: 5845, R01-NS081077, R01-EB014922, the Garen & Shari Staglin and the International Mental Health Research Organization. K. Jann has a fellowship funded by SNSF/SSMBS (grant no. 142743).

                Article
                10.1002/brb3.358
                4589806
                26445698
                b4ad09ad-4f09-4fe2-afd0-4608c6598747
                © 2015 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 February 2015
                : 27 March 2015
                : 12 May 2015
                Categories
                Original Research

                Neurosciences
                arterial spin labeling,autism spectrum disorder,cerebral blood flow,default mode network,dorsal acc,functional connectivity

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