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Reduced limbic microstructural integrity in functional neurological disorder

Published online by Cambridge University Press:  26 November 2019

Ibai Diez
Affiliation:
Department of Neurology, Functional Neurology Research Group, Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Nuclear Medicine, Gordon Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Neurotechnology Laboratory, Tecnalia Health Department, Derio, Spain
Benjamin Williams
Affiliation:
Department of Neurology, Functional Neurology Research Group, Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Marek R. Kubicki
Affiliation:
Department of Psychiatry, Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Nikos Makris
Affiliation:
Department of Psychiatry, Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Radiology, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
David L. Perez*
Affiliation:
Department of Neurology, Functional Neurology Research Group, Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Psychiatry, Neuropsychiatry Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
*
Author for correspondence: David L. Perez, E-mail: dlperez@partners.org

Abstract

Background

Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration.

Methods

A diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons.

Results

Compared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients.

Conclusions

In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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