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A framework for understanding the pathophysiology of functional neurological disorder

Published online by Cambridge University Press:  04 September 2020

Daniel L. Drane
Departments of Neurology and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
Negar Fani
Department of Psychiatry and Behavioral Sciences, Emory School of Medicine, Atlanta, Georgia, USA
Mark Hallett
Human Motor Control Section, NINDS, National Institutes of Health, Bethesda, Maryland, USA
Sahib S. Khalsa
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA Oxley College of Health Sciences, The University of Tulsa, Tulsa, Oklahoma, USA
David L. Perez*
Cognitive Behavioral Neurology and Neuropsychiatry Units, Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Nicole A. Roberts
School of Social and Behavioral Sciences, Arizona State University, Phoenix, Arizona, USA
*Author for correspondence: David L. Perez MD, MMSc, Email:


The symptoms of functional neurological disorder (FND) are a product of its pathophysiology. The pathophysiology of FND is reflective of dysfunction within and across different brain circuits that, in turn, affects specific constructs. In this perspective article, we briefly review five constructs that are affected in FND: emotion processing (including salience), agency, attention, interoception, and predictive processing/inference. Examples of underlying neural circuits include salience, multimodal integration, and attention networks. The symptoms of each patient can be described as a combination of dysfunction in several of these networks and related processes. While we have gained a considerable understanding of FND, there is more work to be done, including determining how pathophysiological abnormalities arise as a consequence of etiologic biopsychosocial factors. To facilitate advances in this underserved and important area, we propose a pathophysiology-focused research agenda to engage government-sponsored funding agencies and foundations.

© The Author(s), 2020. Published by Cambridge University Press

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All authors contributed equally to this study.


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