Abstract
BACKGROUND: Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration. METHODS: A diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons. RESULTS: Compared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients. CONCLUSIONS: In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.