Altered functional connectivity related to prepulse inhibition in functional movement disorder

Area of Science:

• Neuroscience
• Clinical Neurology
• Systems Neuroscience

Background:

• Functional neurological disorder (FND) is increasingly recognized as a complex, multinetwork disorder.
• Deficits in sensorimotor gating, indicated by reduced prepulse inhibition (PPI) of the startle reflex, are observed in FND, suggesting impaired sensory input filtering.
• The neural mechanisms connecting impaired gating to intrinsic network dysfunction in FND remain unclear.

Purpose of the Study:

• To investigate the relationship between sensorimotor gating (PPI) and resting-state functional connectivity in patients with functional movement disorder (FMD).
• To identify the neural correlates of impaired gating in FMD by examining functional connectivity patterns.

Main Methods:

• Compared PPI of the blink reflex and resting-state functional connectivity (seed-based connectivity analysis) between 38 FMD patients and 39 healthy controls (HC).
• Utilized the CONN toolbox with a default atlas for whole-brain connectivity analyses.
• Examined group-by-PPI interactions to determine if associations between PPI and connectivity differed between FMD patients and HC.

Main Results:

• FMD patients demonstrated significantly reduced PPI compared to HC.
• Significant group-by-PPI interactions were found in the bilateral temporoparietal junction (TPJ), linked to insular cortex and supramarginal gyrus seeds.
• In HC, higher PPI correlated with stronger insula-TPJ and inter-TPJ connectivity; these associations were absent in FMD patients.

Conclusions:

• Effective sensorimotor gating relies on functional coupling within insula-TPJ circuits, crucial for salience and ventral attention networks.
• Disrupted insula-TPJ network modulation in FMD suggests impaired top-down sensory filtering.
• This provides a mechanistic link between sensory processing deficits and aberrant salience network dynamics in FMD.