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Research paper
Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders
  1. David L Perez1,2,3,
  2. Nassim Matin1,
  3. Arthur Barsky4,
  4. Victor Costumero-Ramos5,
  5. Sara J Makaretz1,6,
  6. Sigrid S Young1,
  7. Jorge Sepulcre3,
  8. W Curt LaFranceJr7,
  9. Matcheri S Keshavan8,
  10. Bradford C Dickerson3,6
  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, Harvard Medical School, Boston, Massachusetts, USA
  3. 3 Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
  4. 4 Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  5. 5 Department of Methodology, University of Valencia, Valencia, Spain
  6. 6 Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  7. 7 Neuropsychiatry and Behavioral Neurology Division, Departments of Psychiatry and Neurology, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, Rhode Island, USA
  8. 8 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr David L Perez, Massachusetts General Hospital, Departments of Neurology and Psychiatry 149 13 th Street, Charlestown, MA 02129, USA; dlperez{at}


Objective Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas.

Methods This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects.

Results Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume.

Conclusions This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified.

  • Conversion Disorder
  • Functional Movement Disorders
  • Functional Weakness
  • Psychogenic Nonepileptic Seizures
  • Voxel-Based Morphometry

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  • DLP and NM are joint first authors.

  • Funding DLP was funded by the NINDS R25NS065743-05S1, Dupont-Warren Fellowship, Massachusetts General Hospital Physician/Scientist Development Award and the Sidney R. Baer, Jr. Foundation. This work was also supported by the Shared Instrumentation Grant 1S10RR023401.

  • Competing interests None declared.

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

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