Mega-analysis of Structural Brain Imaging in Functional Neurological Disorder

Despite recent advances, the pathophysiology of functional neurological disorder (FND) remains incompletely understood. Structural neuroimaging studies have identified grey matter alterations in somatomotor, salience, limbic, and default mode network associated areas, although findings are inconsistent. Mega-analyses, which combine individual-level data across studies, can help clarify structural alterations.

We conducted a mega-analysis of brain structural morphometrics derived from T1-weighed MRI scans from fifteen international research groups. After across-site harmonisation with ComBat, we compared 493 functional motor and seizure patients with 564 healthy controls. Euler numbers were included to account for head motion.

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 & 0.23), bilateral superior precentral sulcus (d = 0.22 & 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); 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.

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 characterisation of FND research cohorts will help further contextualise the biological relevance of structural alterations.