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      Is functional brain connectivity atypical in autism? A systematic review of EEG and MEG studies

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          Abstract

          Background

          Although it is well recognized that autism is associated with altered patterns of over- and under-connectivity, specifics are still a matter of debate. Little has been done so far to synthesize available literature using whole-brain electroencephalography (EEG) and magnetoencephalography (MEG) recordings.

          Objectives

          1) To systematically review the literature on EEG/MEG functional and effective connectivity in autism spectrum disorder (ASD), 2) to synthesize and critically appraise findings related with the hypothesis that ASD is characterized by long-range underconnectivity and local overconnectivity, and 3) to provide, based on the literature, an analysis of tentative factors that are likely to mediate association between ASD and atypical connectivity (e.g., development, topography, lateralization).

          Methods

          Literature reviews were done using PubMed and PsychInfo databases. Abstracts were screened, and only relevant articles were analyzed based on the objectives of this paper. Special attention was paid to the methodological characteristics that could have created variability in outcomes reported between studies.

          Results

          Our synthesis provides relatively strong support for long-range underconnectivity in ASD, whereas the status of local connectivity remains unclear. This observation was also mirrored by a similar relationship with lower frequencies being often associated with underconnectivity and higher frequencies being associated with both under- and over-connectivity. Putting together these observations, we propose that ASD is characterized by a general trend toward an under-expression of lower-band wide-spread integrative processes compensated by more focal, higher-frequency, locally specialized, and segregated processes. Further investigation is, however, needed to corroborate the conclusion and its generalizability across different tasks. Of note, abnormal lateralization in ASD, specifically an elevated left-over-right EEG and MEG functional connectivity ratio, has been also reported consistently across studies.

          Conclusions

          The large variability in study samples and methodology makes a systematic quantitative analysis (i.e. meta-analysis) of this body of research impossible. Nevertheless, a general trend supporting the hypothesis of long-range functional underconnectivity can be observed. Further research is necessary to more confidently determine the status of the hypothesis of short-range overconnectivity. Frequency-band specific patterns and their relationships with known symptoms of autism also need to be further clarified.

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          Most cited references194

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          Mechanisms of gamma oscillations.

          Gamma rhythms are commonly observed in many brain regions during both waking and sleep states, yet their functions and mechanisms remain a matter of debate. Here we review the cellular and synaptic mechanisms underlying gamma oscillations and outline empirical questions and controversial conceptual issues. Our main points are as follows: First, gamma-band rhythmogenesis is inextricably tied to perisomatic inhibition. Second, gamma oscillations are short-lived and typically emerge from the coordinated interaction of excitation and inhibition, which can be detected as local field potentials. Third, gamma rhythm typically concurs with irregular firing of single neurons, and the network frequency of gamma oscillations varies extensively depending on the underlying mechanism. To document gamma oscillations, efforts should be made to distinguish them from mere increases of gamma-band power and/or increased spiking activity. Fourth, the magnitude of gamma oscillation is modulated by slower rhythms. Such cross-frequency coupling may serve to couple active patches of cortical circuits. Because of their ubiquitous nature and strong correlation with the "operational modes" of local circuits, gamma oscillations continue to provide important clues about neuronal population dynamics in health and disease.
            • Record: found
            • Abstract: found
            • Article: not found

            Abnormal neural oscillations and synchrony in schizophrenia.

            Converging evidence from electrophysiological, physiological and anatomical studies suggests that abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of schizophrenia. Neural oscillations are a fundamental mechanism for the establishment of precise temporal relationships between neuronal responses that are in turn relevant for memory, perception and consciousness. In patients with schizophrenia, the synchronization of beta- and gamma-band activity is abnormal, suggesting a crucial role for dysfunctional oscillations in the generation of the cognitive deficits and other symptoms of the disorder. Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (gamma-aminobutyric acid) interneurons and in cortico-cortical connections.
              • Record: found
              • Abstract: found
              • Article: not found

              The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism

              Autism spectrum disorders (ASD) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, life-long nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. While the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE) – a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) datasets with corresponding structural MRI and phenotypic information from 539 individuals with ASD and 573 age-matched typical controls (TC; 7–64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 males with ASD and 403 male age-matched TC. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo and hyperconnectivity in the ASD literature; both were detected, though hypoconnectivity dominated, particularly for cortico-cortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASD (mid and posterior insula, posterior cingulate cortex), and highlighted less commonly explored regions such as thalamus. The survey of the ABIDE R-fMRI datasets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international datasets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 May 2017
                2017
                : 12
                : 5
                : e0175870
                Affiliations
                [1 ]Douglas Mental Health University Institute, 6875 Boulevard Lasalle, Verdun, Canada
                [2 ]Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, QC, Canada
                [3 ]McGill Center for Integrative Neuroscience, Montreal Neurological Institute, McGill University, 3801 University Street, Montréal, QC, Canada
                Istituto Italiano di Tecnologia, ITALY
                Author notes

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

                • Conceptualization: CO JL ME.

                • Funding acquisition: ME.

                • Investigation: CO.

                • Methodology: CO ME.

                • Project administration: ME.

                • Supervision: ME.

                • Visualization: CO.

                • Writing – original draft: CO.

                • Writing – review & editing: CO JL ME.

                [¤]

                Current address: Blue Brain Projet, École Polytechnique Fédérale de Lausanne, Campus Biotech, Chemin des Mines 9, Geneva, Switzerland

                Author information
                http://orcid.org/0000-0002-3149-4934
                Article
                PONE-D-16-34600
                10.1371/journal.pone.0175870
                5414938
                28467487
                3f57db78-5241-4991-bc93-a59fc21726e2
                © 2017 O’Reilly et al

                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
                : 31 August 2016
                : 31 March 2017
                Page count
                Figures: 2, Tables: 1, Pages: 28
                Funding
                Funded by: Bourgeois Foundation
                Award Recipient :
                Funded by: Fonds de Recherche du Québec - Santé (CA)
                Award Recipient :
                Funded by: funder-id https://doi.org/10.13039/100009408, Fondation Brain Canada;
                Award Recipient :
                Funded by: funder-id https://doi.org/10.13039/501100005155, Azrieli Foundation;
                Award ID: BC_Azrieli_MIRI_3388
                Award Recipient :
                This work is supported by grants from the Fonds de recherche du Québec – Santé (FRQS; http://www.frqs.gouv.qc.ca/en/), Bourgeois Foundation, Brain Canada ( http://www.braincanada.ca/), and the Azrieli Foundation (grant number BC_Azrieli_MIRI_3388; http://www.azrielifoundation.org/) attributed to ME. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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