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      The Imaginary Part of Coherency in Autism: Differences in Cortical Functional Connectivity in Preschool Children

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          Abstract

          Cognition arises from the transient integration and segregation of activity across functionally distinct brain areas. Autism Spectrum Disorders (ASD), which encompass a wide range of developmental disabilities, have been presumed to be associated with a problem in cortical and sub-cortical dynamics of coordinated activity, often involving enhanced local but decreased long range coordination over areas of integration. In this paper we challenge this idea by presenting results from a relatively large population of ASD children and age-matched controls during a face-processing task. Over most of the explored domain, children with ASD exhibited enhanced synchronization, although finer detail reveals specific enhancement/reduction of synchrony depending on time, frequency and brain site. Our results are derived from the use of the imaginary part of coherency, a measure which is not susceptible to volume conduction artifacts and therefore presents a credible picture of coordinated brain activity. We also present evidence that this measure is a good candidate to provide features in building a classifier to be used as a potential biomarker for autism.

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          Identifying true brain interaction from EEG data using the imaginary part of coherency.

          The main obstacle in interpreting EEG/MEG data in terms of brain connectivity is the fact that because of volume conduction, the activity of a single brain source can be observed in many channels. Here, we present an approach which is insensitive to false connectivity arising from volume conduction. We show that the (complex) coherency of non-interacting sources is necessarily real and, hence, the imaginary part of coherency provides an excellent candidate to study brain interactions. Although the usual magnitude and phase of coherency contain the same information as the real and imaginary parts, we argue that the Cartesian representation is far superior for studying brain interactions. The method is demonstrated for EEG measurements of voluntary finger movement. We found: (a) from 5 s before to movement onset a relatively weak interaction around 20 Hz between left and right motor areas where the contralateral side leads the ipsilateral side; and (b) approximately 2-4 s after movement, a stronger interaction also at 20 Hz in the opposite direction. It is possible to reliably detect brain interaction during movement from EEG data. The method allows unambiguous detection of brain interaction from rhythmic EEG/MEG data.
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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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              EEG coherency. I: Statistics, reference electrode, volume conduction, Laplacians, cortical imaging, and interpretation at multiple scales.

              Several methodological issues which impact experimental design and physiological interpretations in EEG coherence studies are considered, including reference electrode and volume conduction contributions to erroneous coherence estimates. A new measure, 'reduced coherency', is introduced as the difference between measured coherency and the coherency expected from uncorrelated neocortical sources, based on simulations and analytic-statistical studies with a volume conductor model. The concept of reduced coherency is shown to be in semi-quantitative agreement with experimental EEG data. The impact of volume conduction on statistical confidence intervals for coherence estimates is discussed. Conventional reference, average reference, bipolar, Laplacian, and cortical image coherencies are shown to be partly independent measures of neocortical dynamic function at different spatial scales, due to each method's unique spatial filtering of intracranial source activity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                1 October 2013
                : 8
                : 10
                : e75941
                Affiliations
                [1 ]Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
                [2 ]Milton and Ethel Harris Research Initiative, York University, Toronto, Ontario, Canada
                [3 ]Neuroscience and Mental Health Programme, Brain and Behaviour Centre, Division of Neurology, Hospital for Sick Children; Department of Paediatrics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
                Bellvitge Biomedical Research Institute-IDIBELL, Spain
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JS SS. Performed the experiments: JS. Analyzed the data: LGD. Contributed reagents/materials/analysis tools: LGD. Wrote the paper: LGD JLPV JS.

                Article
                PONE-D-12-14884
                10.1371/journal.pone.0075941
                3788049
                24098409
                62c8f3b7-7478-4b80-8baf-952afe2e4ab1
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 May 2012
                : 23 August 2013
                Page count
                Pages: 13
                Funding
                This research was made possible by the generous support of the Harris Steel Foundation and the Harris family, which made it possible to create the Milton and Ethel Harris Research Initiative ( www.mehri.ca). The authors have also received support from the Unicorn Foundation, Cure Autism Now, the Public Health Agency of Canada, the Templeton Foundation, York University, and the facilities of the Shared Hierarchical Academic Research Computing Network (SHARCNET: www.sharcnet.ca) and Compute/Calcul Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Research Article

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