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Research paper
Corticolimbic structural alterations linked to health status and trait anxiety in functional neurological disorder
  1. David L Perez1,2,3,
  2. Benjamin Williams1,
  3. Nassim Matin1,
  4. W Curt LaFrance Jr4,
  5. Victor Costumero-Ramos5,6,
  6. Gregory L Fricchione7,
  7. Jorge Sepulcre3,
  8. Matcheri S Keshavan8,
  9. Bradford C Dickerson3,9
  1. 1 Department of Neurology, Functional Neurology Research Group, Cognitive Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  2. 2 Department of Psychiatry, Neuropsychiatry Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
  3. 3 Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, USA
  4. 4 Neuropsychiatry and Behavioral Neurology Division, Departments of Psychiatry and Neurology, Rhode Island Hospital, Brown University, Alpert Medical School, Providence, Rhode Island, USA
  5. 5 Department of Methodology, University of Valencia, Valencia, Spain
  6. 6 Department of Basic and Clinical Psychology and Psychobiology, University Jaume I, Castellón de la Plana, Spain
  7. 7 Department of Psychiatry, Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  8. 8 Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
  9. 9 Department of Neurology, Frontotemporal Disorders Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr David L Perez, Massachusetts General Hospital, Departments of Neurology and Psychiatry 149 13th Street, Charlestown, MA 02129; dlperez{at}


Objective Affective symptoms influence health status (health-related quality of life) in functional neurological disorder (FND), and the salience network is implicated in the pathophysiology of FND and mood/anxiety disorders. We hypothesised that self-reported health status and affective symptoms would map onto salience network regions and that patients with FND would show decreased insular volumes compared with controls.

Methods This voxel-based morphometry study investigated volumetric differences in 26 patients with FND (21 women, 5 men; mean age=40.3±11.5) compared with 27 healthy controls (22 women, 5 men; mean age=40.5±10.8). Post hoc analyses stratified patients with FND by mental and physical health scores (Short Form Health Survey-36). Within-group analyses investigated associations with mental health, physical health, trait anxiety and depression in patients with FND.

Results There were no volumetric differences between the complete FND cohort and controls. In stratified analyses, however, patients with FND reporting the most severe physical health impairments showed reduced left anterior insular volume compared with controls. In within-group analyses, impaired mental health and elevated trait anxiety were associated with increased right amygdalar volumes in patients with FND. The relationship between amygdalar volume and mental health, driven by emotional well-being deficits and role limitations due to emotional problems, was independent of sensorimotor functional neurological symptom severity and motor FND subtype. In secondary within-group analyses, increased periaqueductal grey volume was associated with role limitations due to emotional problems. Impaired physical functioning correlated with decreased left anterior insular volumes.

Conclusions These findings support roles for several regions of the salience network in the pathophysiology of FND.

  • conversion disorder
  • functional movement disorders
  • psychogenic nonepileptic seizures
  • voxel-based morphometry
  • insula

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  • Contributors DLP, WCL, MSK and BCD designed the study. DLP, BW and NM collected the data. DLP, BW, NM and VC-R performed the analyses. DLP and BW drafted the manuscript. All authors critically interpreted the results and critically revised the manuscript.

  • Funding DLP was funded by the Dupont Warren and Livingston Fellowships, Massachusetts General Hospital Physician-Scientist Development Award, and the Sidney R. Baer Jr. Foundation.

  • Competing interests BCD: consultant at Merck, Med Learning Group and Haymarket; royalties from Oxford University Press and Cambridge University Press; on the editorial board of Neuroimage: Clinical, Cortex, Hippocampus, Neurodegenerative Disease Management. MSK: consultant at Forum Pharmaceuticals; editor for Schizophrenia Research. WCL has served on the editorial boards of Epilepsia, Epilepsy & Behavior 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. (2017); author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); has received research support from the NIH (NINDS 5K23NS45902 [PI]), Rhode Island Hospital, the American Epilepsy Society (AES), the Epilepsy Foundation (EF), Brown University and the Siravo Foundation; serves on the Epilepsy Foundation Professional Advisory Board; has received honoraria for the American Academy of Neurology Annual Meeting Annual Course; has served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health and Emory University; and has provided medico legal expert testimony. All other authors report no conflicts of interest.

  • Patient consent Obtained.

  • Ethics approval Partners Human Research Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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