Given that the multimodal integration network (insula, dorsal anterior cingulate, temporoparietal junction (TPJ)) is implicated in sensory-motor, affective and interoceptive processing, we hypothesized that functional neurological disorder (FND) patients would exhibit altered motor and amygdalar resting-state propagation to this network. Symptom severity and clinical outcome were also hypothesized to map onto multimodal integration areas.

Individuals with FND frequently exhibit motor and affective disturbances, along with limbic hyper-reactivity and enhanced motor-limbic connectivity. However, the pathways through which motor and limbic areas interact remain poorly understood. 

Between-group differences in primary motor and amygdalar sub-nuclei (laterobasal, centromedial) were examined using graph-theory stepwise functional connectivity (SFC) in 30 patients with motor FND compared to 30 healthy controls. Within-group analyses correlated SFC profiles with symptom severity and prospectively collected 6-month outcomes (Screening for Somatoform Symptoms Conversion Disorder subscale and Patient Health Questionnaire-15 composite score). Findings were cluster-wise corrected for multiple comparisons.

Compared to controls, patients with FND exhibited increased SFC from motor regions to the bilateral posterior insula, TPJ, supplementary motor area (SMA), and putamen. From the right laterobasal amygdala, the FND cohort showed enhanced connectivity to the left anterior insula, periaqueductal gray and hypothalamus. Patient-reported symptom severity correlated with enhanced link-step connectivity from the left anterior insula to the right anterior insula and TPJ; increased SFC from the left centromedial amygdala to the right anterior insula correlated with 6-month clinical improvement. Within-group associations held controlling for depression, anxiety and antidepressant use.

We identified enhanced propagation from primary motor and laterobasal amygdala to areas implicated in salience, interoception, stress responses and self/emotional awareness. Altered link-step connectivity from the left anterior insula to the right anterior insula and TPJ related to symptom severity; centromedial amygdala–anterior insula interactions require more study as a possible outcome biomarker. These findings suggest candidate neurocircuit pathways in the pathophysiology of FND.