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      Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study

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          Abstract

          Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.

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          Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity.

          The brain activation of a group of high-functioning autistic participants was measured using functional MRI during sentence comprehension and the results compared with those of a Verbal IQ-matched control group. The groups differed in the distribution of activation in two of the key language areas. The autism group produced reliably more activation than the control group in Wernicke's (left laterosuperior temporal) area and reliably less activation than the control group in Broca's (left inferior frontal gyrus) area. Furthermore, the functional connectivity, i.e. the degree of synchronization or correlation of the time series of the activation, between the various participating cortical areas was consistently lower for the autistic than the control participants. These findings suggest that the neural basis of disordered language in autism entails a lower degree of information integration and synchronization across the large-scale cortical network for language processing. The article presents a theoretical account of the findings, related to neurobiological foundations of underconnectivity in autism.
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            Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity.

            It is commonly assumed that functional brain connectivity reflects structural brain connectivity. The exact relationship between structure and function, however, might not be straightforward. In this review we aim to examine how our understanding of the relationship between structure and function in the 'resting' brain has advanced over the last several years. We discuss eight articles that directly compare resting-state functional connectivity with structural connectivity and three clinical case studies of patients with limited white matter connections between the cerebral hemispheres. All studies examined show largely convergent results: the strength of resting-state functional connectivity is positively correlated with structural connectivity strength. However, functional connectivity is also observed between regions where there is little or no structural connectivity, which most likely indicates functional correlations mediated by indirect structural connections (i.e. via a third region). As the methodologies for measuring structural and functional connectivity continue to improve and their complementary strengths are applied in parallel, we can expect important advances in our diagnostic and prognostic capacities in diseases like Alzheimer's, multiple sclerosis, and stroke.
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              Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task.

              Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy.
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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
                18 June 2013
                : 8
                : 6
                : e67329
                Affiliations
                [1 ]Institute of Clinical Radiology, Ludwig-Maximilians University Munich, Munich, Germany
                [2 ]Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University Munich, Munich, Germany
                [3 ]Department of Psychology, Stanford University, Stanford, California, United States of America
                [4 ]Department of Neurology, Ludwig-Maximilians University Munich, Munich, Germany
                [5 ]German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University Munich, Munich, Germany
                [6 ]Department of Psychiatry, University of Rostock, Rostock, Germany
                [7 ]Department of Psychology, Ludwig-Maximilians University Munich, Munich, Germany
                Centre Hospitalier Universitaire Vaudois Lausanne - CHUV, UNIL, Switzerland
                Author notes

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

                Conceived and designed the experiments: SM DK KHF TM. Performed the experiments: AS UC MH JB. Analyzed the data: SM DK MG KHF OE. Contributed reagents/materials/analysis tools: VK MFR TM OE. Wrote the paper: SM.

                Article
                PONE-D-12-26704
                10.1371/journal.pone.0067329
                3688993
                23825652
                8261c36a-9ba4-4fe4-b2c9-e6c5d582387b
                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
                : 30 August 2012
                : 19 May 2013
                Page count
                Pages: 11
                Funding
                This study was supported by internal funds of the Department of Psychology and the Institute of Clinical Radiology, Ludwig Maximilians University Munich. Sophia Mueller receives a research fellowship from the German Research Foundation (MU 3222/2-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Neuroscience
                Computational Neuroscience
                Neural Networks
                Neuroimaging
                Medicine
                Mental Health
                Psychiatry
                Neuropsychiatric Disorders
                Psychology
                Cognitive Psychology
                Neurology
                Radiology

                Uncategorized
                Uncategorized

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