Breathlessness catastrophising after COVID-19 involves both interoceptive and visceromotor connectivity

Abstract

Persistent breathlessness is common after COVID-19, yet its severity typically correlates weakly with objective clinical measures. This discordance is often attributed to perceptual inference amplified by anxiety. Because breathing involves a closed perception-action loop, breathlessness may also reflect alterations in interoceptive and visceromotor pathways. We acquired 7-tesla resting-state functional MRI in 53 post-COVID patients with varying breathlessness and estimated functional connectivity across 18 pre-defined interoceptive and visceromotor regions. Linear regression identified two connections associated with breathlessness catastrophising: reduced dorsal periaqueductal grey-posterior insula (dPAG-PoI1) and increased basolateral amygdala-dorsal anterior cingulate (BLA-dACC) connectivity. The dPAG-PoI1 association was stronger in patients who had required mechanical ventilation, whereas the BLA-dACC association was attenuated at higher generalised anxiety. These findings are consistent with two potentially separable contributions to symptom burden: weakened interoceptive signalling between brainstem and sensory cortex, and heightened visceromotor influence of threat processing on autonomic control, rather than anxiety-driven misperception alone.