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      Dysconnectivity of Multiple Brain Networks in Schizophrenia: A Meta-Analysis of Resting-State Functional Connectivity

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          Abstract

          Background: Seed-based studies on resting-state functional connectivity (rsFC) in schizophrenia have shown disrupted connectivity involving a number of brain networks; however, the results have been controversial.

          Methods: We conducted a meta-analysis based on independent component analysis (ICA) brain templates to evaluate dysconnectivity within resting-state brain networks in patients with schizophrenia. Seventy-six rsFC studies from 70 publications with 2,588 schizophrenia patients and 2,567 healthy controls (HCs) were included in the present meta-analysis. The locations and activation effects of significant intergroup comparisons were extracted and classified based on the ICA templates. Then, multilevel kernel density analysis was used to integrate the results and control bias.

          Results: Compared with HCs, significant hypoconnectivities were observed between the seed regions and the areas in the auditory network (left insula), core network (right superior temporal cortex), default mode network (right medial prefrontal cortex, and left precuneus and anterior cingulate cortices), self-referential network (right superior temporal cortex), and somatomotor network (right precentral gyrus) in schizophrenia patients. No hyperconnectivity between the seed regions and any other areas within the networks was detected in patients, compared with the connectivity in HCs.

          Conclusions: Decreased rsFC within the self-referential network and default mode network might play fundamental roles in the malfunction of information processing, while the core network might act as a dysfunctional hub of regulation. Our meta-analysis is consistent with diffuse hypoconnectivities as a dysregulated brain network model of schizophrenia.

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          Most cited references111

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          Emotional processing in anterior cingulate and medial prefrontal cortex.

          Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions. Published by Elsevier Ltd.
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            Electrophysiological signatures of resting state networks in the human brain.

            Functional neuroimaging and electrophysiological studies have documented a dynamic baseline of intrinsic (not stimulus- or task-evoked) brain activity during resting wakefulness. This baseline is characterized by slow (<0.1 Hz) fluctuations of functional imaging signals that are topographically organized in discrete brain networks, and by much faster (1-80 Hz) electrical oscillations. To investigate the relationship between hemodynamic and electrical oscillations, we have adopted a completely data-driven approach that combines information from simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Using independent component analysis on the fMRI data, we identified six widely distributed resting state networks. The blood oxygenation level-dependent signal fluctuations associated with each network were correlated with the EEG power variations of delta, theta, alpha, beta, and gamma rhythms. Each functional network was characterized by a specific electrophysiological signature that involved the combination of different brain rhythms. Moreover, the joint EEG/fMRI analysis afforded a finer physiological fractionation of brain networks in the resting human brain. This result supports for the first time in humans the coalescence of several brain rhythms within large-scale brain networks as suggested by biophysical studies.
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              The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology.

              The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                12 July 2019
                2019
                : 10
                : 482
                Affiliations
                [1] 1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University , Chengdu, China
                [2] 2Department of Radiology, West China Hospital, Sichuan University , Chengdu, China
                [3] 3Department of Psychoradiology, Chengdu Mental Health Center , Chengdu, China
                [4] 4Department of Geriatric Psychiatry, The Fourth People’s Hospital of Chengdu , Chengdu, China
                [5] 5Department of Psychiatry, Zigong Mental Health Center , Zigong, China
                Author notes

                Edited by: André Schmidt, University of Basel, Switzerland

                Reviewed by: Matthias Kirschner, Psychiatrische Klinik der Universität Zürich, Switzerland; Debo Dong, University of Electronic Science and Technology of China, China

                *Correspondence: Su Lui, lusuwcums@ 123456tom.com

                This article was submitted to Neuroimaging and Stimulation, a section of the journal Frontiers in Psychiatry

                †These authors have contributed equally to this work.

                Article
                10.3389/fpsyt.2019.00482
                6639431
                31354545
                d40d177b-a722-4fdc-adb6-9ce607f3cffd
                Copyright © 2019 Li, Hu, Zhang, Tao, Dai, Gong, Tan, Cai and Lui

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 February 2019
                : 19 June 2019
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 146, Pages: 11, Words: 4230
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Categories
                Psychiatry
                Systematic Review

                Clinical Psychology & Psychiatry
                schizophrenia,resting state,magnetic resonance imaging,functional connectivity,brain network,meta-analysis

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