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      Widespread brain dysconnectivity associated with psychotic-like experiences in the general population

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          Abstract

          It is becoming increasingly clear that psychosis occurs along a continuum. At the high end are formal psychotic disorders such as schizophrenia, and at the low-end are individuals who experience occasional psychotic symptoms, but are otherwise healthy (non-clinical psychosis, NCP). Schizophrenia has been shown to be marked by altered patterns of connectivity between brain regions, but it is not known if such dysconnectivity exists in NCP. In the current study we used functional magnetic resonance imaging (fMRI) to compare resting-state functional connectivity in NCP individuals ( n = 25) and healthy controls ( n = 27) for four brain networks of interest (fronto-parietal, cingulo-opercular, default mode, and cerebellar networks). NCP individuals showed reduced connectivity compared to controls between regions of the default mode network and frontal regions, and between regions in all of the networks and the thalamus. NCP individuals showed greater connectivity compared to controls within regions of frontal control networks. Further, positive symptom scores in NCP individuals were positively correlated with connectivity between the cingulo-opercular network and the visual cortex, and were negatively correlated with connectivity between the cerebellar network and the posterior parietal cortex and dorsal premotor cortex. Connectivity was not correlated with positive symptom scores in controls. Taken together, these findings demonstrate that a spectrum of abnormal connectivity underlies the psychosis continuum, and that individuals with sub-clinical psychotic experiences represent a key population for understanding pathogenic processes.

          Highlights

          • We compared resting state connectivity in controls and non-clinical psychosis (NCP).

          • NCP showed disrupted connectivity in control, default-mode and cerebellum regions.

          • Disrupted connectivity was associated with positive symptom scores.

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          The attention system of the human brain.

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            Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization.

            Resting state functional connectivity MRI (fcMRI) is widely used to investigate brain networks that exhibit correlated fluctuations. While fcMRI does not provide direct measurement of anatomic connectivity, accumulating evidence suggests it is sufficiently constrained by anatomy to allow the architecture of distinct brain systems to be characterized. fcMRI is particularly useful for characterizing large-scale systems that span distributed areas (e.g., polysynaptic cortical pathways, cerebro-cerebellar circuits, cortical-thalamic circuits) and has complementary strengths when contrasted with the other major tool available for human connectomics-high angular resolution diffusion imaging (HARDI). We review what is known about fcMRI and then explore fcMRI data reliability, effects of preprocessing, analysis procedures, and effects of different acquisition parameters across six studies (n = 98) to provide recommendations for optimization. Run length (2-12 min), run structure (1 12-min run or 2 6-min runs), temporal resolution (2.5 or 5.0 s), spatial resolution (2 or 3 mm), and the task (fixation, eyes closed rest, eyes open rest, continuous word-classification) were varied. Results revealed moderate to high test-retest reliability. Run structure, temporal resolution, and spatial resolution minimally influenced fcMRI results while fixation and eyes open rest yielded stronger correlations as contrasted to other task conditions. Commonly used preprocessing steps involving regression of nuisance signals minimized nonspecific (noise) correlations including those associated with respiration. The most surprising finding was that estimates of correlation strengths stabilized with acquisition times as brief as 5 min. The brevity and robustness of fcMRI positions it as a powerful tool for large-scale explorations of genetic influences on brain architecture. We conclude by discussing the strengths and limitations of fcMRI and how it can be combined with HARDI techniques to support the emerging field of human connectomics.
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              Patterns of brain activity supporting autobiographical memory, prospection, and theory of mind, and their relationship to the default mode network.

              The ability to rise above the present environment and reflect upon the past, the future, and the minds of others is a fundamentally defining human feature. It has been proposed that these three self-referential processes involve a highly interconnected core set of brain structures known as the default mode network (DMN). The DMN appears to be active when individuals are engaged in stimulus-independent thought. This network is a likely candidate for supporting multiple processes, but this idea has not been tested directly. We used fMRI to examine brain activity during autobiographical remembering, prospection, and theory-of-mind reasoning. Using multivariate analyses, we found a common pattern of neural activation underlying all three processes in the DMN. In addition, autobiographical remembering and prospection engaged midline DMN structures to a greater degree and theory-of-mind reasoning engaged lateral DMN areas. A functional connectivity analysis revealed that activity of a critical node in the DMN, medial prefrontal cortex, was correlated with activity in other regions in the DMN during all three tasks. We conclude that the DMN supports common aspects of these cognitive behaviors involved in simulating an internalized experience.
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                Author and article information

                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                18 January 2014
                18 January 2014
                2014
                : 4
                : 343-351
                Affiliations
                [a ]University of Colorado Boulder, Institute for Cognitive Science, USA
                [b ]Mind Research Network, Translational Neuroscience Department, USA
                [c ]Georgia State University, Department of Psychology and Neuroscience Institute, USA
                [d ]University of Colorado Boulder, Department of Psychology and Neuroscience, USA
                [e ]University of Colorado Boulder, Center for Neuroscience, USA
                Author notes
                [* ]Corresponding author at: 1777 Exposition Dr. CINC 182D Boulder, CO 80309, USA. Tel.: + 1 303 735 2553. Joseph.orr@ 123456colorado.edu
                Article
                S2213-1582(14)00007-2
                10.1016/j.nicl.2014.01.006
                3913833
                24501703
                23023b84-860f-4881-af43-7e79d6554997
                © 2014 The Authors
                History
                : 15 October 2013
                : 20 December 2013
                : 9 January 2014
                Categories
                Article

                non-clinical psychosis,continuum,default mode network,connectivity,resting-state

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