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

David L Perez¹, Timothy R Nicholson², Ali A Asadi-Pooya³, Indrit Bègue⁴, Matthew Butler², Alan J Carson⁵, Anthony S David⁶, Quinton Deeley⁷, Ibai Diez⁸, Mark J Edwards⁹, Alberto J Espay¹⁰, Jeannette M Gelauff¹¹, Mark Hallett¹², Silvina G Horovitz¹², Johannes Jungilligens¹³, Richard A A Kanaan¹⁴, Marina A J Tijssen¹⁵, Kasia Kozlowska¹⁶, Kathrin LaFaver¹⁷, W Curt LaFrance Jr¹⁸, Sarah C Lidstone¹⁹, Ramesh S Marapin¹⁵, Carine W Maurer²⁰, Mandana Modirrousta²¹, Antje A T S Reinders²², Petr Sojka²³, Jeffrey P Staab²⁴, Jon Stone⁵, Jerzy P Szaflarski²⁵, Selma Aybek²⁶

Affiliations

¹ Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: dlperez@nmr.mgh.harvard.edu.
² Section of Cognitive Neuropsychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³ Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz Iran; Department of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, Philadelphia, PA, USA.
⁴ Division of Adult Psychiatry, Department of Psychiatry, University of Geneva, Geneva Switzerland; Service of Neurology Department of Clinical Neuroscience, University of Geneva, Geneva, Switzerland.
⁵ Centre for Clinical Brain Sciences, The University of Edinburgh, EH16 4SB, UK.
⁶ Institute of Mental Health, University College London, London, UK.
⁷ South London and Maudsley NHS Foundation Trust, London UK Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
⁸ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Neurosciences Research Centre, St George's University of London, London, UK.
¹⁰ James J. and Joan A. Gardner Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
¹¹ Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, Amsterdam, Netherlands.
¹² Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
¹³ Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Germany.
¹⁴ Department of Psychiatry, University of Melbourne, Austin Health Heidelberg, Australia.
¹⁵ Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Groningen, University of Groningen, The Netherlands.
¹⁶ The Children's Hospital at Westmead, Westmead Institute of Medical Research, University of Sydney Medical School, Sydney, NSW, Australia.
¹⁷ Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
¹⁸ Departments of Psychiatry and Neurology, Rhode Island Hospital, Brown University, Providence, RI, USA.
¹⁹ 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.
²⁰ Department of Neurology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA.
²¹ Department of Psychiatry, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
²² Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²³ Department of Psychiatry, University Hospital Brno, Czech Republic.
²⁴ Departments of Psychiatry and Psychology and Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic Rochester, MN, USA.
²⁵ University of Alabama at Birmingham Epilepsy Center, Department of Neurology, University of Alabama at Birmingham Birmingham, AL, USA.
²⁶ Neurology Department, Psychosomatic Medicine Unit, Bern University Hospital Inselspital, University of Bern, Bern, Switzerland.

PMID: 34215138
PMCID: PMC8111317
DOI: 10.1016/j.nicl.2021.102623

Review

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

David L Perez et al. Neuroimage Clin. 2021.

. 2021:30:102623.

doi: 10.1016/j.nicl.2021.102623. Epub 2021 Mar 11.

Authors

Affiliations

¹ Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: dlperez@nmr.mgh.harvard.edu.
² Section of Cognitive Neuropsychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³ Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz Iran; Department of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, Philadelphia, PA, USA.
⁴ Division of Adult Psychiatry, Department of Psychiatry, University of Geneva, Geneva Switzerland; Service of Neurology Department of Clinical Neuroscience, University of Geneva, Geneva, Switzerland.
⁵ Centre for Clinical Brain Sciences, The University of Edinburgh, EH16 4SB, UK.
⁶ Institute of Mental Health, University College London, London, UK.
⁷ South London and Maudsley NHS Foundation Trust, London UK Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
⁸ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Neurosciences Research Centre, St George's University of London, London, UK.
¹⁰ James J. and Joan A. Gardner Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
¹¹ Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, Amsterdam, Netherlands.
¹² Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
¹³ Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Germany.
¹⁴ Department of Psychiatry, University of Melbourne, Austin Health Heidelberg, Australia.
¹⁵ Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Groningen, University of Groningen, The Netherlands.
¹⁶ The Children's Hospital at Westmead, Westmead Institute of Medical Research, University of Sydney Medical School, Sydney, NSW, Australia.
¹⁷ Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
¹⁸ Departments of Psychiatry and Neurology, Rhode Island Hospital, Brown University, Providence, RI, USA.
¹⁹ 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.
²⁰ Department of Neurology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA.
²¹ Department of Psychiatry, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
²² Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²³ Department of Psychiatry, University Hospital Brno, Czech Republic.
²⁴ Departments of Psychiatry and Psychology and Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic Rochester, MN, USA.
²⁵ University of Alabama at Birmingham Epilepsy Center, Department of Neurology, University of Alabama at Birmingham Birmingham, AL, USA.
²⁶ Neurology Department, Psychosomatic Medicine Unit, Bern University Hospital Inselspital, University of Bern, Bern, Switzerland.

PMID: 34215138
PMCID: PMC8111317
DOI: 10.1016/j.nicl.2021.102623

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.

Keywords: Conversion disorder; DTI; Functional neurological disorder; MRI; Neuroimaging; fMRI.

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References

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

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

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