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      Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder

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          Abstract

          Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical–cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical–cerebellar networks and visuomotor impairments in ASD have not yet been clarified.

          Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined.

          Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex.

          Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar–cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.

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          Most cited references69

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          Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

          In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.
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            Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations.

            A previous report of correlations in low-frequency resting-state fluctuations between right and left hemisphere motor cortices in rapidly sampled single-slice echoplanar data is confirmed using a whole-body echoplanar MRI scanner at 1.5 T. These correlations are extended to lower sampling rate multislice echoplanar acquisitions and other right/left hemisphere-symmetric functional cortices. The specificity of the correlations in the lower sampling-rate acquisitions is lower due to cardiac and respiratory-cycle effects which are aliased into the pass-band of the low-pass filter. Data are combined for three normal right-handed male subjects. Correlations to left hemisphere motor cortex, visual cortex, and amygdala are measured in long resting-state scans.
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              Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity.

              The brain activation of a group of high-functioning autistic participants was measured using functional MRI during sentence comprehension and the results compared with those of a Verbal IQ-matched control group. The groups differed in the distribution of activation in two of the key language areas. The autism group produced reliably more activation than the control group in Wernicke's (left laterosuperior temporal) area and reliably less activation than the control group in Broca's (left inferior frontal gyrus) area. Furthermore, the functional connectivity, i.e. the degree of synchronization or correlation of the time series of the activation, between the various participating cortical areas was consistently lower for the autistic than the control participants. These findings suggest that the neural basis of disordered language in autism entails a lower degree of information integration and synchronization across the large-scale cortical network for language processing. The article presents a theoretical account of the findings, related to neurobiological foundations of underconnectivity in autism.
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                Author and article information

                Contributors
                Journal
                Front Integr Neurosci
                Front Integr Neurosci
                Front. Integr. Neurosci.
                Frontiers in Integrative Neuroscience
                Frontiers Media S.A.
                1662-5145
                31 May 2019
                2019
                : 13
                : 17
                Affiliations
                [1] 1Department of Occupational Therapy, University of Florida , Gainesville, FL, United States
                [2] 2Huaxi Magnetic Resonance Research Center, Department of Radiology, West China Hospital of Sichuan University , Chengdu, China
                [3] 3Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine , Cincinnati, OH, United States
                [4] 4Schiefelbusch Institute for Life Span Studies, University of Kansas , Lawrence, KS, United States
                [5] 5Clinical Child Psychology Program, University of Kansas , Lawrence, KS, United States
                [6] 6Kansas Center for Autism Research and Training, University of Kansas , Lawrence, KS, United States
                Author notes

                Edited by: Thomas W. James, Indiana University Bloomington, United States

                Reviewed by: Elias Manjarrez, Meritorious Autonomous University of Puebla, Mexico; Wei Liao, University of Electronic Science and Technology of China, China

                *Correspondence: Su Lui lusuwcums@ 123456hotmail.com
                Matthew W. Mosconi mosconi@ 123456ku.edu

                †These authors share first authorship

                Article
                10.3389/fnint.2019.00017
                6554427
                31213995
                cbe912e9-95b2-458d-a109-40e234eb4eac
                Copyright © 2019 Wang, Wang, Sweeney, Gong, Lui and Mosconi.

                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) and the copyright owner(s) 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
                : 29 January 2019
                : 06 May 2019
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 91, Pages: 14, Words: 10603
                Funding
                Funded by: National Institute of Mental Health 10.13039/100000025
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development 10.13039/100009633
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Categories
                Neuroscience
                Original Research

                Neurosciences
                autism spectrum disorder,resting-state functional mri,visuomotor control,precision grip,cortical–cerebellar connectivity,amplitude of low-frequency fluctuations,functional connectivity

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