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      Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale

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          Abstract

          Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8-18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-α rhythm. In contrast, the mu-β rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-β was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism group, P < 0.01 and P < 0.0001 for the typical group), with autism severity (P < 0.03), and with diagnosis (89% accuracy). A biophysically realistic computational model using data driven feedforward and feedback parameters replicated the magnetoencephalography data faithfully. The direct observation of both abnormally increased and abnormally decreased functional connectivity in autism occurring simultaneously in different functional connectivity streams, offers a potential unifying framework for the unexplained discrepancies in current findings. Given that cortical feedback, whether local or long-range, is intrinsically non-linear, while cortical feedforward is generally linear relative to the stimulus, the present results suggest decreased non-linearity alongside an increased veridical component of the cortical response in autism.

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          Cortical surface-based analysis. I. Segmentation and surface reconstruction.

          Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging. Copyright 1999 Academic Press.
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            Nonparametric statistical testing of EEG- and MEG-data.

            In this paper, we show how ElectroEncephaloGraphic (EEG) and MagnetoEncephaloGraphic (MEG) data can be analyzed statistically using nonparametric techniques. Nonparametric statistical tests offer complete freedom to the user with respect to the test statistic by means of which the experimental conditions are compared. This freedom provides a straightforward way to solve the multiple comparisons problem (MCP) and it allows to incorporate biophysically motivated constraints in the test statistic, which may drastically increase the sensitivity of the statistical test. The paper is written for two audiences: (1) empirical neuroscientists looking for the most appropriate data analysis method, and (2) methodologists interested in the theoretical concepts behind nonparametric statistical tests. For the empirical neuroscientist, a large part of the paper is written in a tutorial-like fashion, enabling neuroscientists to construct their own statistical test, maximizing the sensitivity to the expected effect. And for the methodologist, it is explained why the nonparametric test is formally correct. This means that we formulate a null hypothesis (identical probability distribution in the different experimental conditions) and show that the nonparametric test controls the false alarm rate under this null hypothesis.
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              Spectrum estimation and harmonic analysis

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                Author and article information

                Journal
                Brain
                Brain
                Oxford University Press (OUP)
                0006-8950
                1460-2156
                April 23 2015
                May 2015
                May 2015
                March 12 2015
                : 138
                : 5
                : 1394-1409
                Article
                10.1093/brain/awv043
                25765326
                7fb33778-26de-4de4-8fb0-c7b25cfd6dde
                © 2015
                History

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