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Anterior hippocampal grey matter predicts mental health outcome in functional neurological disorders: an exploratory pilot study
  1. David L Perez1,2,3,
  2. Benjamin Williams1,
  3. Nassim Matin1,
  4. Julie Mello4,
  5. Bradford C Dickerson3,5,
  6. W Curt LaFrance Jr6,7,
  7. Matcheri S Keshavan8
  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 Department of Physical Therapy, Massachusetts General Hospital, Boston, Massachusetts, USA
  5. 5 Department of Neurology, Frontotemporal Disorders Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
  6. 6 Neuropsychiatry and Behavioral Neurology Division, Rhode Island Hospital, Providence, Rhode Island, USA
  7. 7 Departments of Psychiatry and Neurology, Brown University, Alpert Medical School, Providence, Rhode Island, USA
  8. 8 Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr David L Perez, Departments of Neurology and Psychiatry, Massachusetts General Hospital, Boston, MA 02129, USA; dlperez{at}

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Advancements in the management of FND emphasise a ‘rule-in’ diagnosis and roles for cognitive behavioural therapy (CBT)1 and physical therapy (PT).2 Neuroimaging studies have also started delineating the neuropathophysiology of FND.3 In the same cohort as this present study, we previously identified that impaired mental health and increased trait anxiety correlated with individual differences in amygdalar volume in patients with FND, while diminished physical functioning was associated with reduced anterior insular volume.4 In FND, the magnitude of adverse life event burden also correlated with decreased insular and hippocampal volumes.5

This pilot voxel-based morphometry (VBM) study used a within-group design to investigate the relationship between baseline volumetric profiles and prospectively collected 6-month outcome data in 22 patients with FND. Stratified comparative analyses with 27 controls were performed to contextualise statistically significant within-group findings. Based on the outcome literature6 and previously described corticolimbic associations with health status and adverse life events,4 5 we hypothesised that baseline amygdalar–hippocampal and cingulo-insular volumes would predict clinical outcomes in FND.


Methods were adapted from Perez et al.4


Twenty-two subjects with FND (19 women, 3 men; age=41.7±11.0 years; illness duration=3.9±4.6 years) were recruited from the Massachusetts General Hospital (MGH) FND Clinic with baseline (MRI+psychometric data) and follow-up (psychometric only) data collected at 6.4±1.1 months; 4 of 26 initial patients were lost to follow-up. Twenty-seven healthy controls (22 women, 5 men; age=40.5±10.8 years) were also recruited through local advertisements.

Patients met criteria for clinically established functional movement disorders (n=12), documented (n=8) or clinically established (n=1) psychogenic non-epileptic seizures and/or exhibited signs of functional weakness (n=9). Eight had mixed symptoms. Inclusion/exclusion criteria were as previously described.4 Psychiatric comorbidities were assessed through the Structured Clinical Interview for DSM-IV-TR. Nineteen patients were on psychotropic medications at baseline (online supplementary table 1 …

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  • WCLFJ and MSK contributed equally.

  • Contributors DLP, MSK, WCL and BCD: designed the study. DLP, BW and NM: collected and analysed the data. DLP: drafted the manuscript. All authors: critically interpreted the data and critically reviewed and edited the manuscript.

  • Funding DLP was funded by the National Institute of Mental Health Grant 1K23MH111983-01A1, Sidney R Baer Jr. Foundation and the Massachusetts General Hospital Physician-Scientist Development Award.

  • Disclaimer BCD is a consultant at Merck, Med Learning Group and Haymarket; received royalties from Oxford University Press and Cambridge University Press; on the editorial board of NeuroImage: Clinical, Cortex, Hippocampus, Neurodegenerative Disease Management. MSK is a consultant at Forum Pharmaceuticals; editor for Schizophrenia Research. WCL has served on the editorial boards of Epilepsia, Epilepsy & Behavior and Journal of Neuropsychiatry & Clinical Neurosciences; receives editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures, 3rd edition (Cambridge University Press, 2010) and 4th edition (2017); receives 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 (principal investigator)), Department of Defense, 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 medicolegal expert testimony.

  • Competing interests None declared.

  • Ethics approval Partners Human Research Committee.

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

  • Correction notice Since this letter was first published online the author surname LaFrance has been updated to include the suffix Jr.