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      Motor cortex facilitation: a marker of attention deficit hyperactivity disorder co-occurrence in autism spectrum disorder

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          Abstract

          The neural correlates distinguishing youth with Autism Spectrum Disorder (ASD-) and ASD with co-occurring Attention Deficit Hyperactivity Disorder (ASD+) are poorly understood despite significant phenotypic and prognostic differences. Paired-pulse transcranial magnetic stimulation (TMS) measures, including intracortical facilitation (ICF), short interval cortical inhibition (SICI), and cortical silent period (CSP) were measured in an age matched cohort of youth with ASD- ( n = 20), ASD + ( n = 29), and controls (TDC) ( n = 24). ASD− and ASD+ groups did not differ by IQ or social functioning; however, ASD+ had significantly higher inattention and hyperactivity ratings. ICF (higher ratio indicates greater facilitation) in ASD+ (Mean 1.0, SD 0.19) was less than ASD− (Mean 1.3, SD 0.36) or TDC (Mean 1.2, SD 0.24) (F2,68 = 6.5, p = 0.003; post-hoc tests, ASD+ vs either TDC or ASD−, p ≤ 0.05). No differences were found between groups for SICI or age corrected active/resting motor threshold (AMT/RMT). Across all ASD youth (ASD− and ASD+), ICF was inversely correlated with worse inattention (Conners-3 Inattention (r = −0.41; p < 0.01) and ADHDRS-IV Inattention percentile (r = −0.422, p < 0.01) scores. ICF remains intact in ASD− but is impaired in ASD+. Lack of ICF is associated with inattention and executive function across ASD. Taken with the present findings, ADHD may have a distinct electrophysiological “signature” in ASD youth. ICF may constitute an emerging biomarker to study the physiology of ADHD in ASD, which may align with disease prognosis or treatment response.

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

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            TMS and drugs revisited 2014.

            The combination of pharmacology and transcranial magnetic stimulation to study the effects of drugs on TMS-evoked EMG responses (pharmaco-TMS-EMG) has considerably improved our understanding of the effects of TMS on the human brain. Ten years have elapsed since an influential review on this topic has been published in this journal (Ziemann, 2004). Since then, several major developments have taken place: TMS has been combined with EEG to measure TMS evoked responses directly from brain activity rather than by motor evoked potentials in a muscle, and pharmacological characterization of the TMS-evoked EEG potentials, although still in its infancy, has started (pharmaco-TMS-EEG). Furthermore, the knowledge from pharmaco-TMS-EMG that has been primarily obtained in healthy subjects is now applied to clinical settings, for instance, to monitor or even predict clinical drug responses in neurological or psychiatric patients. Finally, pharmaco-TMS-EMG has been applied to understand the effects of CNS active drugs on non-invasive brain stimulation induced long-term potentiation-like and long-term depression-like plasticity. This is a new field that may help to develop rationales of pharmacological treatment for enhancement of recovery and re-learning after CNS lesions. This up-dated review will highlight important knowledge and recent advances in the contribution of pharmaco-TMS-EMG and pharmaco-TMS-EEG to our understanding of normal and dysfunctional excitability, connectivity and plasticity of the human brain. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
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              Shared and distinct intrinsic functional network centrality in autism and attention-deficit/hyperactivity disorder.

              Individuals with autism spectrum disorders (ASD) often exhibit symptoms of attention-deficit/hyperactivity disorder (ADHD). Across both disorders, observations of distributed functional abnormalities suggest aberrant large-scale brain network connectivity. Yet, common and distinct network correlates of ASD and ADHD remain unidentified. Here, we aimed to examine patterns of dysconnection in school-age children with ASD and ADHD and typically developing children who completed a resting state functional magnetic resonance imaging scan. We measured voxelwise network centrality, functional connectivity metrics indexing local (degree centrality [DC]) and global (eigenvector centrality) functional relationships across the entire brain connectome, in resting state functional magnetic resonance imaging data from 56 children with ASD, 45 children with ADHD, and 50 typically developing children. A one-way analysis of covariance, with group as fixed factor (whole-brain corrected), was followed by post hoc pairwise comparisons. Cortical and subcortical areas exhibited centrality abnormalities, some common to both ADHD and ASD, such as in precuneus. Others were disorder-specific and included ADHD-related increases in DC in right striatum/pallidum, in contrast with ASD-related increases in bilateral temporolimbic areas. Secondary analyses differentiating children with ASD into those with or without ADHD-like comorbidity (ASD(+) and ASD(-), respectively) revealed that the ASD(+) group shared ADHD-specific abnormalities in basal ganglia. By contrast, centrality increases in temporolimbic areas characterized children with ASD regardless of ADHD-like comorbidity. At the cluster level, eigenvector centrality group patterns were similar to DC. ADHD and ASD are neurodevelopmental disorders with distinct and overlapping clinical presentations. This work provides evidence for both shared and distinct underlying mechanisms at the large-scale network level. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                +1 513 636 4222 , ernest.pedapati@cchmc.org
                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group UK (London )
                2158-3188
                13 November 2019
                13 November 2019
                2019
                : 9
                : 298
                Affiliations
                [1 ]ISNI 0000 0000 9025 8099, GRID grid.239573.9, Divisions of Child and Adolescent Psychiatry, , Cincinnati Children’s Hospital Medical Center, ; Cincinnati, OH USA
                [2 ]ISNI 0000 0000 9025 8099, GRID grid.239573.9, Division of Neurology, , Cincinnati Children’s Hospital Medical Center, ; Cincinnati, OH USA
                [3 ]ISNI 0000 0004 1936 9684, GRID grid.27860.3b, Department of Psychology, , University of California, ; Davis, CA USA
                [4 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Department of Psychiatry, , University of Cincinnati College of Medicine, ; Cincinnati, OH USA
                [5 ]ISNI 0000 0000 9025 8099, GRID grid.239573.9, Developmental and Behavioral Pediatrics, , Cincinnati Children’s Hospital Medical Center, ; Cincinnati, OH USA
                [6 ]ISNI 0000 0000 9025 8099, GRID grid.239573.9, Divisions of Biostatistics and Epidemiology, , Cincinnati Children’s Hospital Medical Center, ; Cincinnati, OH USA
                Author information
                http://orcid.org/0000-0002-4990-5754
                Article
                614
                10.1038/s41398-019-0614-3
                6853984
                31723120
                3471ba97-a4a6-4c86-a642-fd302d14b5ee
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 April 2019
                : 23 September 2019
                : 15 October 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100005337, American Academy of Child and Adolescent Psychiatry (American Academy of Child & Adolescent Psychiatry);
                Award ID: Junior Investigator Award
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);
                Award ID: 5K23MH112936
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Clinical Psychology & Psychiatry
                diagnostic markers,physiology
                Clinical Psychology & Psychiatry
                diagnostic markers, physiology

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