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

Research output: Contribution to journalReview articlepeer-review

Antje A. T. S. Reinders, David L. Perez, Timothy Nicholson, Ali Asadi-Pooya, Indrit Bègue, Matthew Butler, Allan J. Carson, Anthony David

Original languageEnglish
Article number102623
Pages (from-to)1-15
Number of pages15
JournalNeuroImage: Clinical
Volume30
Early online date11 Mar 2021
DOIs
Accepted/In press3 Mar 2021
E-pub ahead of print11 Mar 2021
Published2 May 2021

Bibliographical note

Funding Information: D.L.P. was funded by the National Institute of Mental Health Grant K23MH111983 and the Sidney R. Baer Jr. Foundation. I.B. is funded by the University of Geneva and University Hospitals of Geneva. M.H. and S.H. are supported by the NINDS Intramural Program. W.C.L. and J.P.Sz. received support from the Office of the Assistant Secretary of Defense for Health Affairs, Epilepsy Research Program Award No. W81XWH-17-1-0619. K.L. has received funding from the Ayers Foundation. C.W.M. has received funding from the Parkinson’s Foundation. J.P.St. was funded by the U.S. Army Medical Research Acquisition Activity, Complex Traumatic Brain Injury Rehabilitation Research – Clinical Research Award W81XWH-18-1-0760. J.S. is supported by a National Research Scotland Career Fellowship Grant. A.A.T.S. is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. SA was supported by a Swiss National Research Foundation grant PP00P3_176985/1. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, US Department of Defense, NHS, the NIHR, or the Department of Health. Funding Information: D.L.P., honoraria from Harvard Medical School for continuing medical education lectures on FND and serves on the editorial board of Epilepsy & Behavior. A.A.A.P, Honoraria from Cobel Daruo, RaymandRad and Tekaje; Royalty: Oxford University Press (Book royalties). A.J.C., paid associate editor of Journal of Neurology, Neurosurgery and Psychiatry (JNNP) and provides expert testimony in court on a range of neuropsychiatric topics including FND. A.J.E., grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Acadia, Acorda, Kyowa Kirin, Sunovion, Lundbeck, and USWorldMeds; honoraria from USWorldMeds, Acadia, and Sunovion; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. M.H., inventor of patents held by NIH for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulation; in relation to the latter, received license fee payments from the NIH (from Brainsway); on the Medical Advisory Boards of CALA Health and Brainsway; research grants from Allergan for studies of methods to inject botulinum toxins, Medtronic, Inc. for a study of DBS for dystonia, and CALA Health for studies of a device to suppress tremor. W.C.L., has served on the editorial boards of Epilepsia, Epilepsy & Behavior, JNNP, and Journal of Neuropsychiatry and Clinical Neurosciences; receives editor's royalties from the publication of Gates and Rowan's Nonepileptic Seizures, 3rd ed (Cambridge University Press, 2010) and 4th ed (2018); receives author's royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); received research support from the US Department of Defense (W81XWH-17-0169), National Institutes of Health (NIH; NINDS 5K23NS45902 [principal investigator]), PVAMC, Center for Neurorestoration and Neurorehabilitation, Rhode Island Hospital, the American Epilepsy Society (AES), the Epilepsy Foundation, Brown University, and the Siravo Foundation; on the Epilepsy Foundation New England Professional Advisory Board, the FND Society Board of Directors, and the American Neuropsychiatric Association Advisory Council; received honoraria for the AES Annual Meeting; served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health, Emory University, and Oregon Health Sciences University; and provided medicolegal expert testimony. K.L., honoraria from the American Academy of Neurology and the International Parkinson and Movement Disorder Society, personal compensation for scientific advisory boards from Acorda. J.S., royalties from UpToDate and carries out expert witness work in relation to FND; runs a free website for people with FND, www.neurosymptoms.org. J.P.S., funded by the NIH, National Science Foundation, US Department of Defense (W81XWH-17-0169), State of Alabama, Shor Foundation for Epilepsy Research, UCB Pharma, NeuroPace, Greenwich Biosciences, Biogen, Xenon Pharmaceuticals, Serina Therapeutics, and Eisai; served on consulting/advisory boards for Greenwich Biosciences, NeuroPace, Serina Therapeutics, LivaNova, UCB Pharma, Lundbeck, and Elite Medical Experts; and serves as an editorial board member for Epilepsy & Behavior, Journal of Epileptology (Associate Editor), Epilepsy & Behavior Reports (Associate Editor), Journal of Medical Science, Epilepsy Currents (Contributing Editor), and Folia Medica Copernicana. Funding Information: None. D.L.P. was funded by the National Institute of Mental Health Grant K23MH111983 and the Sidney R. Baer Jr. Foundation. I.B. is funded by the University of Geneva and University Hospitals of Geneva. M.H. and S.H. are supported by the NINDS Intramural Program. W.C.L. and J.P.Sz. received support from the Office of the Assistant Secretary of Defense for Health Affairs, Epilepsy Research Program Award No. W81XWH-17-1-0619. K.L. has received funding from the Ayers Foundation. C.W.M. has received funding from the Parkinson's Foundation. J.P.St. was funded by the U.S. Army Medical Research Acquisition Activity, Complex Traumatic Brain Injury Rehabilitation Research ? Clinical Research Award W81XWH-18-1-0760. J.S. is supported by a National Research Scotland Career Fellowship Grant. A.A.T.S. is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. SA was supported by a Swiss National Research Foundation grant PP00P3_176985/1. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, US Department of Defense, NHS, the NIHR, or the Department of Health. D.L.P. honoraria from Harvard Medical School for continuing medical education lectures on FND and serves on the editorial board of Epilepsy & Behavior. A.A.A.P, Honoraria from Cobel Daruo, RaymandRad and Tekaje; Royalty: Oxford University Press (Book royalties). A.J.C. paid associate editor of Journal of Neurology, Neurosurgery and Psychiatry (JNNP) and provides expert testimony in court on a range of neuropsychiatric topics including FND. A.J.E. grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Acadia, Acorda, Kyowa Kirin, Sunovion, Lundbeck, and USWorldMeds; honoraria from USWorldMeds, Acadia, and Sunovion; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. M.H. inventor of patents held by NIH for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulation; in relation to the latter, received license fee payments from the NIH (from Brainsway); on the Medical Advisory Boards of CALA Health and Brainsway; research grants from Allergan for studies of methods to inject botulinum toxins, Medtronic, Inc. for a study of DBS for dystonia, and CALA Health for studies of a device to suppress tremor. W.C.L. has served on the editorial boards of Epilepsia, Epilepsy & Behavior, JNNP, and Journal of Neuropsychiatry and Clinical Neurosciences; receives editor's royalties from the publication of Gates and Rowan's Nonepileptic Seizures, 3rd ed (Cambridge University Press, 2010) and 4th ed (2018); receives author's royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); received research support from the US Department of Defense (W81XWH-17-0169), National Institutes of Health (NIH; NINDS 5K23NS45902 [principal investigator]), PVAMC, Center for Neurorestoration and Neurorehabilitation, Rhode Island Hospital, the American Epilepsy Society (AES), the Epilepsy Foundation, Brown University, and the Siravo Foundation; on the Epilepsy Foundation New England Professional Advisory Board, the FND Society Board of Directors, and the American Neuropsychiatric Association Advisory Council; received honoraria for the AES Annual Meeting; served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health, Emory University, and Oregon Health Sciences University; and provided medicolegal expert testimony. K.L. honoraria from the American Academy of Neurology and the International Parkinson and Movement Disorder Society, personal compensation for scientific advisory boards from Acorda. J.S. royalties from UpToDate and carries out expert witness work in relation to FND; runs a free website for people with FND, www.neurosymptoms.org. J.P.S. funded by the NIH, National Science Foundation, US Department of Defense (W81XWH-17-0169), State of Alabama, Shor Foundation for Epilepsy Research, UCB Pharma, NeuroPace, Greenwich Biosciences, Biogen, Xenon Pharmaceuticals, Serina Therapeutics, and Eisai; served on consulting/advisory boards for Greenwich Biosciences, NeuroPace, Serina Therapeutics, LivaNova, UCB Pharma, Lundbeck, and Elite Medical Experts; and serves as an editorial board member for Epilepsy & Behavior, Journal of Epileptology (Associate Editor), Epilepsy & Behavior Reports (Associate Editor), Journal of Medical Science, Epilepsy Currents (Contributing Editor), and Folia Medica Copernicana. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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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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