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      Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis

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          Abstract

          Background

          Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed.

          Methods

          We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2–32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults ( n = 212 ASD, n = 199 neurotypicals [NT], all with IQ > 75). We performed analyses in source-space using individual head models derived from the participants’ MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%–30% split).

          Results

          In the training dataset, we found an interaction between age and group for the reactivity to eye opening ( p = .042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52–0.62, specificity 0.59–0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset.

          Limitations

          The statistical power to detect weak effects—of the magnitude of those found in the training dataset—in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset’s effects.

          Conclusions

          This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13229-022-00500-x.

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          Most cited references80

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          FieldTrip: Open Source Software for Advanced Analysis of MEG, EEG, and Invasive Electrophysiological Data

          This paper describes FieldTrip, an open source software package that we developed for the analysis of MEG, EEG, and other electrophysiological data. The software is implemented as a MATLAB toolbox and includes a complete set of consistent and user-friendly high-level functions that allow experimental neuroscientists to analyze experimental data. It includes algorithms for simple and advanced analysis, such as time-frequency analysis using multitapers, source reconstruction using dipoles, distributed sources and beamformers, connectivity analysis, and nonparametric statistical permutation tests at the channel and source level. The implementation as toolbox allows the user to perform elaborate and structured analyses of large data sets using the MATLAB command line and batch scripting. Furthermore, users and developers can easily extend the functionality and implement new algorithms. The modular design facilitates the reuse in other software packages.
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            Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016

            Problem/Condition Autism spectrum disorder (ASD). Period Covered 2016. Description of System The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (40% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively). Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). Interpretation The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. Public Health Action These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.
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              Predicting the Future - Big Data, Machine Learning, and Clinical Medicine.

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                Author and article information

                Contributors
                pilar.garces@roche.com
                Journal
                Mol Autism
                Mol Autism
                Molecular Autism
                BioMed Central (London )
                2040-2392
                18 May 2022
                18 May 2022
                2022
                : 13
                : 22
                Affiliations
                [1 ]GRID grid.417570.0, ISNI 0000 0004 0374 1269, Roche Pharma Research and Early Development, Neuroscience and Rare Diseases, , Roche Innovation Center Basel, ; Basel, Switzerland
                [2 ]GRID grid.7700.0, ISNI 0000 0001 2190 4373, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, , Heidelberg University, ; Mannheim, Germany
                [3 ]GRID grid.88379.3d, ISNI 0000 0001 2324 0507, Department of Psychological Sciences, Centre for Brain and Cognitive Development, , Birkbeck, University of London, ; London, UK
                [4 ]GRID grid.8385.6, ISNI 0000 0001 2297 375X, Institute of Neuroscience and Medicine, Brain and Behaviour (INM-7), , Research Centre Jülich, ; Jülich, Germany
                [5 ]GRID grid.411327.2, ISNI 0000 0001 2176 9917, Medical Faculty, Institute of Systems Neuroscience, , Heinrich Heine University Düsseldorf, ; Düsseldorf, Germany
                [6 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Psychiatry, Autism Research Centre, , University of Cambridge, ; Cambridge, UK
                [7 ]GRID grid.467087.a, ISNI 0000 0004 0442 1056, Department of Women’s and Children’s Health, Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, , Karolinska Institutet and Child and Adolescent Psychiatry, Stockholm Health Care Services, ; Region Stockholm, Stockholm, Sweden
                [8 ]GRID grid.1032.0, ISNI 0000 0004 0375 4078, Curtin Autism Research Group, Curtin School of Allied Health, , Curtin University, ; Perth, WA Australia
                [9 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Cognitive Neuroscience, , Donders Institute for Brain, Cognition and Behaviour, Radboudumc, ; Nijmegen, The Netherlands
                [10 ]GRID grid.7692.a, ISNI 0000000090126352, Brain Center Rudolf Magnus, , University Medical Center Utrecht, ; Utrecht, The Netherlands
                [11 ]GRID grid.10438.3e, ISNI 0000 0001 2178 8421, Interdepartmental Program “Autism 0-90”, , “G. Martino” University Hospital, University of Messina, ; Messina, Italy
                [12 ]Human Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université de Paris, Paris, France
                [13 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Institute of Psychiatry, Psychology and Neuroscience, , King’s College, ; London, UK
                [14 ]Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Goethe University, Frankfurt am Main, Germany
                [15 ]GRID grid.7400.3, ISNI 0000 0004 1937 0650, Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, , University of Zurich, ; Zurich, Switzerland
                [16 ]GRID grid.7400.3, ISNI 0000 0004 1937 0650, Neuroscience Center Zurich, University and ETH Zurich, ; Zurich, Switzerland
                Author information
                http://orcid.org/0000-0003-4989-0123
                Article
                500
                10.1186/s13229-022-00500-x
                9118870
                35585637
                40778158-1963-4510-bacc-f19621faed41
                © The Author(s) 2022

                Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 14 September 2021
                : 6 May 2022
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Neurosciences
                autism spectrum disorder,eeg,resting state,power spectrum,functional connectivity
                Neurosciences
                autism spectrum disorder, eeg, resting state, power spectrum, functional connectivity

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