Mega-Analysis of Structural Brain Imaging in Functional Neurological Disorder
Abstract
BACKGROUND:: Despite recent advances, the pathophysiology of functional neurological disorder (FND) remains incompletely understood. Structural neuroimaging studies have identified gray matter alterations in somatomotor-, salience-, limbic-, and default mode network–associated areas, although findings have been inconsistent. Mega-analyses, which combine individual-level data across studies, can help clarify structural alterations.
METHODS:: We conducted a mega-analysis of brain structural morphometrics derived from T1-weighted magnetic resonance imaging scans from 15 international research groups. After across-site harmonization with ComBat, we compared 493 patients with functional motor disorder and functional seizures with 564 healthy control participants. Euler numbers were included to account for head motion.
RESULTS:: The FND cohort showed reduced cortical thickness in the bilateral superior frontal gyri (left d = 0.22, right d = 0.21) and sulci (d = 0.22 and 0.23), bilateral superior precentral sulcus (d = 0.22 and 0.26), right precentral gyrus (d = 0.25), right paracentral gyrus and sulcus (d = 0.23), right cuneus (d = 0.23), and right inferior opercular gyrus (d = 0.21); we also found reduced left postcentral gyrus surface area (d = 0.25) and right hippocampal volume (d = 0.22). No regions were different in relative surface area. There were no associations between morphometrics and illness duration or lifetime history of depression or anxiety. Differences between motor and seizure variants were not identified.
CONCLUSIONS:: This large mega-analysis suggests subtle morphometric differences, particularly in prefrontal and motor regions. This may represent predisposing vulnerabilities, compensatory mechanisms, or FND-specific alterations. Improved neuropsychiatric characterization of FND research cohorts will help further contextualize the biological relevance of structural alterations.
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BibTeX
@article{butler2026megaanalysis,
title = {{Mega-Analysis of Structural Brain Imaging in Functional Neurological Disorder}},
author = {Matt Butler and Miriam Vignando and Jane B. Allendorfer and Thomas Hassa and Silvina G. Horovitz and Jacobus F.A. Jansen and Johannes Jungilligens and Wesley T. Kerr and Ramesh S. Marapin and Enrico Premi and Aleksandar J. Ristic and Tereza Serranova and Petr Sojka and Daichi Sone and Barbara Borroni and Anthony David and Quinton Deeley and Ibai Diez and Sara Paredes Echeverri and Dawn S. Elashiv and Jeannette M. Gelauff and Mark Hallett and Richard Kanaan and Marina A.J. de Koning-Tijssen and Madeleine Love and Mauro Magoni and Kirpal Sadheura and Noriko Salamon and Noriko Sato and Ariel Schoenfeld and John M. Stern and Jerzy P. Szaflarski and David L. Perez and Selma Aybek and Mitul A. Mehta and Timothy Nicholson},
journal = {Biological psychiatry},
year = {2026},
month = jul,
doi = {10.1016/j.biopsych.2026.06.031},
url = {https://europepmc.org/article/PMC/PMC13719111},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mega-Analysis of Structural Brain Imaging in Functional Neurological Disorder
AU - Matt Butler
AU - Miriam Vignando
AU - Jane B. Allendorfer
AU - Thomas Hassa
AU - Silvina G. Horovitz
AU - Jacobus F.A. Jansen
AU - Johannes Jungilligens
AU - Wesley T. Kerr
AU - Ramesh S. Marapin
AU - Enrico Premi
AU - Aleksandar J. Ristic
AU - Tereza Serranova
AU - Petr Sojka
AU - Daichi Sone
AU - Barbara Borroni
AU - Anthony David
AU - Quinton Deeley
AU - Ibai Diez
AU - Sara Paredes Echeverri
AU - Dawn S. Elashiv
AU - Jeannette M. Gelauff
AU - Mark Hallett
AU - Richard Kanaan
AU - Marina A.J. de Koning-Tijssen
AU - Madeleine Love
AU - Mauro Magoni
AU - Kirpal Sadheura
AU - Noriko Salamon
AU - Noriko Sato
AU - Ariel Schoenfeld
AU - John M. Stern
AU - Jerzy P. Szaflarski
AU - David L. Perez
AU - Selma Aybek
AU - Mitul A. Mehta
AU - Timothy Nicholson
PY - 2026
DA - 2026/07/10
JO - Biological psychiatry
DO - 10.1016/j.biopsych.2026.06.031
UR - https://europepmc.org/article/PMC/PMC13719111
AB - BACKGROUND:: Despite recent advances, the pathophysiology of functional neurological disorder (FND) remains incompletely understood. Structural neuroimaging studies have identified gray matter alterations in somatomotor-, salience-, limbic-, and default mode network–associated areas, although findings have been inconsistent. Mega-analyses, which combine individual-level data across studies, can help clarify structural alterations. METHODS:: We conducted a mega-analysis of brain structural morphometrics derived from T1-weighted magnetic resonance imaging scans from 15 international research groups. After across-site harmonization with ComBat, we compared 493 patients with functional motor disorder and functional seizures with 564 healthy control participants. Euler numbers were included to account for head motion. RESULTS:: The FND cohort showed reduced cortical thickness in the bilateral superior frontal gyri (left d = 0.22, right d = 0.21) and sulci (d = 0.22 and 0.23), bilateral superior precentral sulcus (d = 0.22 and 0.26), right precentral gyrus (d = 0.25), right paracentral gyrus and sulcus (d = 0.23), right cuneus (d = 0.23), and right inferior opercular gyrus (d = 0.21); we also found reduced left postcentral gyrus surface area (d = 0.25) and right hippocampal volume (d = 0.22). No regions were different in relative surface area. There were no associations between morphometrics and illness duration or lifetime history of depression or anxiety. Differences between motor and seizure variants were not identified. CONCLUSIONS:: This large mega-analysis suggests subtle morphometric differences, particularly in prefrontal and motor regions. This may represent predisposing vulnerabilities, compensatory mechanisms, or FND-specific alterations. Improved neuropsychiatric characterization of FND research cohorts will help further contextualize the biological relevance of structural alterations.
SN - 0006-3223
SN - 1873-2402
ER -