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      Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome

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          Abstract

          Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging ( rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

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          Most cited references 45

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          Interoception: the sense of the physiological condition of the body.

          Converging evidence indicates that primates have a distinct cortical image of homeostatic afferent activity that reflects all aspects of the physiological condition of all tissues of the body. This interoceptive system, associated with autonomic motor control, is distinct from the exteroceptive system (cutaneous mechanoreception and proprioception) that guides somatic motor activity. The primary interoceptive representation in the dorsal posterior insula engenders distinct highly resolved feelings from the body that include pain, temperature, itch, sensual touch, muscular and visceral sensations, vasomotor activity, hunger, thirst, and 'air hunger'. In humans, a meta-representation of the primary interoceptive activity is engendered in the right anterior insula, which seems to provide the basis for the subjective image of the material self as a feeling (sentient) entity, that is, emotional awareness.
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            Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases.

            This paper reports the development of a self-report instrument designed to assess pain in cancer and other diseases. It is argued that issues of reliability and validity should be considered for every pain questionnaire. Most research on measures of pain examine reliability to the relative neglect of validity concerns. The Wisconsin Brief Pain Questionnaire (BPQ) is evaluated with regard to both reliability and validity. Data from patients with cancer at 4 primary sites and from patients with rheumatoid arthritis suggest that the BPQ is sufficiently reliable and valid for research purposes. Additional methodological and theoretical issues related to validity are discussed, and the need for continuing evaluation of the BPQ and other measures of clinical pain is stressed.
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              Development of functional and structural connectivity within the default mode network in young children.

              Functional and structural maturation of networks comprised of discrete regions is an important aspect of brain development. The default-mode network (DMN) is a prominent network which includes the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), medial temporal lobes (MTL), and angular gyrus (AG). Despite increasing interest in DMN function, little is known about its maturation from childhood to adulthood. Here we examine developmental changes in DMN connectivity using a multimodal imaging approach by combining resting-state fMRI, voxel-based morphometry and diffusion tensor imaging-based tractography. We found that the DMN undergoes significant developmental changes in functional and structural connectivity, but these changes are not uniform across all DMN nodes. Convergent structural and functional connectivity analyses suggest that PCC-mPFC connectivity along the cingulum bundle is the most immature link in the DMN of children. Both PCC and mPFC also showed gray matter volume differences, as well as prominent macrostructural and microstructural differences in the dorsal cingulum bundle linking these regions. Notably, structural connectivity between PCC and left MTL was either weak or non-existent in children, even though functional connectivity did not differ from that of adults. These results imply that functional connectivity in children can reach adult-like levels despite weak structural connectivity. We propose that maturation of PCC-mPFC structural connectivity plays an important role in the development of self-related and social-cognitive functions that emerge during adolescence. More generally, our study demonstrates how quantitative multimodal analysis of anatomy and connectivity allows us to better characterize the heterogeneous development and maturation of brain networks. Copyright 2010 Elsevier Inc. All rights reserved.
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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, CA USA )
                1932-6203
                14 July 2016
                2016
                : 11
                : 7
                Affiliations
                [1 ]Department of Pediatrics, Akershus University Hospital, Nordbyhagen, Norway
                [2 ]Department of Psychology, University of Oslo, Oslo, Norway
                [3 ]Cognitive Developmental Research Unit, Department of Psychology, University of Oslo, Oslo, Norway
                [4 ]Research Department, Innlandet Hospital Trust, Lillehammer, Norway
                Institute of Psychology, Chinese Academy of Sciences, CHINA
                Author notes

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

                Conceived and designed the experiments: TE AM MØ VBW. Performed the experiments: TE AM MØ VBW. Analyzed the data: LAW AS. Contributed reagents/materials/analysis tools: LAW TE AS. Wrote the paper: LAW VBW MØ TE AM AS.

                Article
                PONE-D-16-08681
                10.1371/journal.pone.0159351
                4944916
                27414048
                © 2016 Wortinger 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.

                Page count
                Figures: 2, Tables: 4, Pages: 16
                Product
                Funding
                Funded by: Norwegian Research Council
                Award ID: 228874
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100006095, Helse Sør-Øst RHF;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100005366, Universitetet i Oslo;
                Award Recipient :
                Norwegian Research Council, http://www.forskningsradet.no/en (VBW, grant number 228874); Health South–East Hospital Trust, http://www.helse-sorost.no/fagfolk_/forskning_/forskningsmidler (VBW); and the University of Oslo, http://www.uio.no/english/ (VBW).
                Categories
                Research Article
                Medicine and Health Sciences
                Neurology
                Neuromuscular Diseases
                Chronic Fatigue Syndrome
                Medicine and Health Sciences
                Rheumatology
                Chronic Fatigue Syndrome
                People and Places
                Population Groupings
                Age Groups
                Adolescents
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fatigue
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fatigue
                Computer and Information Sciences
                Neural Networks
                Biology and Life Sciences
                Neuroscience
                Neural Networks
                Biology and Life Sciences
                Physiology
                Sensory Physiology
                Somatosensory System
                Pain Sensation
                Medicine and Health Sciences
                Physiology
                Sensory Physiology
                Somatosensory System
                Pain Sensation
                Biology and Life Sciences
                Neuroscience
                Sensory Systems
                Somatosensory System
                Pain Sensation
                Biology and Life Sciences
                Neuroscience
                Brain Mapping
                Functional Magnetic Resonance Imaging
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Functional Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Functional Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Functional Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Functional Magnetic Resonance Imaging
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Functional Magnetic Resonance Imaging
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Custom metadata
                All NIFTI files will be available from the OpenfMRI database, https://openfmri.org/ (accession number—ds000173).

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