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      Reduced cortical volume of the default mode network in adolescents with generalized anxiety disorder

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          Abstract

          Background

          Widespread structural alterations have been shown to be implicated in individuals with generalized anxiety disorder (GAD). However, there have been inconsistent findings in cortical volume (CV) differences. Most structural neuroimaging studies looking at GAD used region‐based approach with relatively small sample sizes, let alone be specific to adolescents with GAD. We believe this is the first study to look at CV measures using a network‐based approach in a larger sample of adolescents with GAD. The goal of the current study was to focus on three different brain networks (i.e., Limbic, Frontoparietal, and Default Mode Network [DMN]) in adolescents with GAD.

          Method

          The study involved 81 adolescents with GAD and 112 typically developing (TD) comparison individuals matched on age (15.98 and 15.63 respective means), sex (42F/39M and 45F/67M), and IQ (101.90 and 103.94 respective means). Participants underwent structural MRI. Freesurfer was used to estimate CV (both network‐specific and region‐specific within networks) and region‐specific sub‐cortical volume measures. Multivariate analysis of covariance (MANCOVA; with sex, age, IQ, and intracranial volume [ICV] as potential covariates) was used to estimate group differences.

          Results

          We found significantly lower CV for the DMN in adolescents with GAD, compared with TD individuals. Adolescents with GAD also showed significantly lower hemispheric mean CV of the default‐mode regions (particularly the prefrontal and temporal regions) and the hippocampus, compared with TD individuals.

          Conclusion

          The current findings suggest structural alterations in adolescents with GAD. These structural alterations will need to be addressed when implementing and developing treatments for patients with GAD.

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          Most cited references67

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          An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.

          In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0.835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.
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            The organization of the human cerebral cortex estimated by intrinsic functional connectivity.

            Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.
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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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                Author and article information

                Contributors
                johannah.bashford@boystown.org
                Journal
                Depress Anxiety
                Depress Anxiety
                10.1002/(ISSN)1520-6394
                DA
                Depression and Anxiety
                John Wiley and Sons Inc. (Hoboken )
                1091-4269
                1520-6394
                21 March 2022
                June 2022
                : 39
                : 6 , DEPRESSION AND ANXIETY IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS ( doiID: 10.1002/da.v39.6 )
                : 485-495
                Affiliations
                [ 1 ] Multimodal Clinical Neuroimaging Laboratory (MCNL), Center for Neurobehavioral Research Boys Town National Research Hospital Boys Town Nebraska USA
                [ 2 ] Center for Brain, Biology, and Behavior University of Nebraska‐Lincoln Lincoln Nebraska USA
                [ 3 ] Department of Psychology University of North Dakota Grand Forks North Dakota USA
                [ 4 ] Inpatient Psychiatric Care Unit Boys Town National Research Hospital Boys Town Nebraska USA
                [ 5 ] Child and Adolescent Mental Health Centre, Mental Health Services Capital Region of Denmark Copenhagen Denmark
                Author notes
                [*] [* ] Correspondence Johannah Bashford‐Largo, PLMHP Center for Neurobehavioral Research, Boys Town National Research Hospital, 14015 Flanagan Blvd, Boys Town, NE 68010‐7520, USA.

                Email: johannah.bashford@ 123456boystown.org

                Author information
                http://orcid.org/0000-0002-0128-9526
                http://orcid.org/0000-0003-0629-6036
                Article
                DA23252
                10.1002/da.23252
                9246827
                35312127
                40b9b981-7e8b-4747-b301-d5be74c91f8f
                © 2022 The Authors. Depression and Anxiety published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 03 March 2022
                : 05 August 2021
                : 06 March 2022
                Page count
                Figures: 1, Tables: 4, Pages: 10, Words: 7516
                Funding
                Funded by: National Institute of Mental Health , doi 10.13039/100000025;
                Award ID: K22‐MH109558
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                June 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

                Clinical Psychology & Psychiatry
                adolescents,cortical volume,default mode network,gad,neuroimaging
                Clinical Psychology & Psychiatry
                adolescents, cortical volume, default mode network, gad, neuroimaging

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