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      Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda

      review-article
      a , * , 1 , 2 , b , 1 , 3 , c , 4 , d , 5 , b , 6 , e , 7 , f , 8 , g , 9 , h , 10 , i , 11 , j , 12 , k , 13 , l , 14 , l , 15 , m , 16 , n , 17 , o , 18 , p , 19 , q , 20 , r , 21 , s , 22 , o , 23 , t , 24 , u , 25 , v , 26 , w , 27 , x , 28 , e , 29 , y , 30 , z , 1 , 31
      NeuroImage : Clinical
      Elsevier
      Functional neurological disorder, Conversion disorder, Neuroimaging, fMRI, MRI, DTI

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Highlights

          • 1st Neuroimaging Workgroup Meeting in Functional Neurological Disorder (FND).

          • Underscores the importance of FND cohort characterization in brain imaging research.

          • Details methodological approaches taken in FND neuroimaging research to date.

          • Research agenda proposed to definitely elucidate the neural circuitry of FND.

          • Discussions underway regarding having FND researchers join the ENIGMA consortium.

          Abstract

          Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart – leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using “rule-in” examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

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          Most cited references196

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          Complex network measures of brain connectivity: uses and interpretations.

          Brain connectivity datasets comprise networks of brain regions connected by anatomical tracts or by functional associations. Complex network analysis-a new multidisciplinary approach to the study of complex systems-aims to characterize these brain networks with a small number of neurobiologically meaningful and easily computable measures. In this article, we discuss construction of brain networks from connectivity data and describe the most commonly used network measures of structural and functional connectivity. We describe measures that variously detect functional integration and segregation, quantify centrality of individual brain regions or pathways, characterize patterns of local anatomical circuitry, and test resilience of networks to insult. We discuss the issues surrounding comparison of structural and functional network connectivity, as well as comparison of networks across subjects. Finally, we describe a Matlab toolbox (http://www.brain-connectivity-toolbox.net) accompanying this article and containing a collection of complex network measures and large-scale neuroanatomical connectivity datasets. Copyright (c) 2009 Elsevier Inc. All rights reserved.
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            Voxel-based morphometry--the methods.

            At its simplest, voxel-based morphometry (VBM) involves a voxel-wise comparison of the local concentration of gray matter between two groups of subjects. The procedure is relatively straightforward and involves spatially normalizing high-resolution images from all the subjects in the study into the same stereotactic space. This is followed by segmenting the gray matter from the spatially normalized images and smoothing the gray-matter segments. Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from the two groups are performed. Corrections for multiple comparisons are made using the theory of Gaussian random fields. This paper describes the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with nonuniformity artifact. We provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data. Copyright 2000 Academic Press.
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              White matter integrity, fiber count, and other fallacies: the do's and don'ts of diffusion MRI.

              Diffusion-weighted MRI (DW-MRI) has been increasingly used in imaging neuroscience over the last decade. An early form of this technique, diffusion tensor imaging (DTI) was rapidly implemented by major MRI scanner companies as a scanner selling point. Due to the ease of use of such implementations, and the plausibility of some of their results, DTI was leapt on by imaging neuroscientists who saw it as a powerful and unique new tool for exploring the structural connectivity of human brain. However, DTI is a rather approximate technique, and its results have frequently been given implausible interpretations that have escaped proper critique and have appeared misleadingly in journals of high reputation. In order to encourage the use of improved DW-MRI methods, which have a better chance of characterizing the actual fiber structure of white matter, and to warn against the misuse and misinterpretation of DTI, we review the physics of DW-MRI, indicate currently preferred methodology, and explain the limits of interpretation of its results. We conclude with a list of 'Do's and Don'ts' which define good practice in this expanding area of imaging neuroscience. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                11 March 2021
                2021
                11 March 2021
                : 30
                : 102623
                Affiliations
                [a ]Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
                [b ]Section of Cognitive Neuropsychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
                [c ]Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz Iran; Department of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, Philadelphia, PA, USA
                [d ]Division of Adult Psychiatry, Department of Psychiatry, University of Geneva, Geneva Switzerland; Service of Neurology Department of Clinical Neuroscience, University of Geneva, Geneva, Switzerland
                [e ]Centre for Clinical Brain Sciences, The University of Edinburgh, EH16 4SB, UK
                [f ]Institute of Mental Health, University College London, London, UK
                [g ]South London and Maudsley NHS Foundation Trust, London UK Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, UK
                [h ]Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
                [i ]Neurosciences Research Centre, St George’s University of London, London, UK
                [j ]James J. and Joan A. Gardner Center for Parkinson’s Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA
                [k ]Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, Amsterdam, Netherlands
                [l ]Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
                [m ]Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Germany
                [n ]Department of Psychiatry, University of Melbourne, Austin Health Heidelberg, Australia
                [o ]Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Groningen, University of Groningen, The Netherlands
                [p ]The Children’s Hospital at Westmead, Westmead Institute of Medical Research, University of Sydney Medical School, Sydney, NSW, Australia
                [q ]Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
                [r ]Departments of Psychiatry and Neurology, Rhode Island Hospital, Brown University, Providence, RI, USA
                [s ]Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, University Health Network and the University of Toronto, Toronto, Ontario, Canada
                [t ]Department of Neurology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA
                [u ]Department of Psychiatry, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
                [v ]Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
                [w ]Department of Psychiatry, University Hospital Brno, Czech Republic
                [x ]Departments of Psychiatry and Psychology and Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic Rochester, MN, USA
                [y ]University of Alabama at Birmingham Epilepsy Center, Department of Neurology, University of Alabama at Birmingham Birmingham, AL, USA
                [z ]Neurology Department, Psychosomatic Medicine Unit, Bern University Hospital Inselspital, University of Bern, Bern, Switzerland
                Author notes
                [* ]Corresponding author: Departments of Neurology and Psychiatry, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. dlperez@ 123456nmr.mgh.harvard.edu
                [1]

                Denotes equal contributions.

                [2]

                David L. Perez: 0000-0003-2721-583X.

                [3]

                Timothy R. Nicholson: 0000-0002-2350-2332.

                [4]

                Ali A. Asadi-Pooya: 0000-0002-2598-7601.

                [5]

                Indrit Bègue: 0000-0001-5350-4454.

                [6]

                Matthew Butler: 0000-0002-9734-6539.

                [7]

                Alan J. Carson: 0000-0002-7425-0964.

                [8]

                Anthony S. David: 0000-0003-0967-774X.

                [9]

                Quinton Deeley: 0000-0001-5306-0769.

                [10]

                Ibai Diez: 0000-0001-5769-0178.

                [11]

                Mark J. Edwards: 0000-0002-8283-9015.

                [12]

                Alberto J. Espay: 0000-0002-3389-136X.

                [13]

                Jeannette M. Gelauff: 0000-0001-6639-6771.

                [14]

                Mark Hallett: 0000-0002-3180-6811.

                [15]

                Silvina G. Horovitz: 0000-0002-5501-5918.

                [16]

                Johannes Jungilligens: 0000-0002-4846-8337.

                [17]

                Richard A. Kanaan: 0000-0003-0992-1917.

                [18]

                Marina A. J. Tijssen: 0000-0001-5783-571X.

                [19]

                Kasia Kozlowska: 0000-0002-9578-0753.

                [20]

                Kathrin LaFaver: 0000-0001-5416-894X.

                [21]

                W. Curt LaFrance Jr.: 0000-0002-4901-3852.

                [22]

                Sarah C. Lidstone: 0000-0002-0147-0202.

                [23]

                Ramesh S. Marapin: 0000-0002-6344-7323.

                [24]

                Carine W. Maurer: 0000-0002-7892-7127.

                [25]

                Mandana Modirrousta: 0000-0003-3247-326X.

                [26]

                Antje A. T. S. Reinders: 0000-0002-7987-1532.

                [27]

                Petr Sojka: 0000-0002-7594-7093.

                [28]

                Jeffrey P. Staab: 0000-0002-1516-3131.

                [29]

                Jon Stone: 0000-0001-9829-8092.

                [30]

                Jerzy P. Szaflarski: 0000-0002-5936-6627.

                [31]

                Selma Aybek: 0000-0002-7877-6760.

                Article
                S2213-1582(21)00067-X 102623
                10.1016/j.nicl.2021.102623
                8111317
                34215138
                542d127c-2078-4e34-9111-81827112cfd0
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 16 February 2021
                : 3 March 2021
                Categories
                Review Article

                functional neurological disorder,conversion disorder,neuroimaging,fmri,mri,dti

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