Altered functional connectivity related to prepulse inhibition in functional movement disorder

Functional neurological disorder (FND) is increasingly understood as a multinetwork disorder. Deficits in subcortical sensorimotor gating, indexed by reduced prepulse inhibition (PPI) of the startle reflex, are reported in FND and may reflect impaired filtering and contextual weighting of sensory input. However, the neural correlates linking impaired gating to intrinsic network dysfunction remain unclear.

We examined the relationship between PPI and resting-state functional connectivity in 38 patients with functional movement disorder (FMD) and 39 healthy controls (HC). PPI of the blink reflex was assessed using a standardized neurophysiological paradigm, and seed-based connectivity (SBC) analyses were performed in CONN toolbox using the default atlas comprising cortical and subcortical regions across the whole brain. To investigate a potential interaction between group and PPI size, we tested whether associations between PPI and SBC differed between FMD and HC groups.

FMD patients exhibited significantly reduced PPI compared to HCs. Across several seeds-the left insular cortex, right supramarginal gyrus and bilateral anterior insula-significant Group × PPI interactions emerged in bilateral temporoparietal junction (TPJ). In HCs, higher PPI was associated with stronger connectivity between the insula and TPJ and between bilateral TPJ regions. These relationships were absent in FMD patients.

Our findings demonstrate that effective sensorimotor gating depends on intact functional coupling within insula-TPJ circuits, key nodes of the salience and ventral attention networks. Disrupted modulation of this network in FMD suggests impaired top-down filtering of sensory information, providing a mechanistic link between sensory processing deficits and aberrant salience-network dynamics in FMD.