Resting-state CNS networks in refractory/unexplained chronic cough

<bold>Background:</bold> The neurobiology of refractory/unexplained chronic cough (RUCC) is complex, but CNS mechanisms, including altered sensory processing and top-down control of airway perceptions, are thought to contribute. We evaluated differences in resting state functional MRI (rs-fMRI) networks between RUCC and healthy volunteers (HV). In RUCC we evaluated wether rs-fMRI differed accross sexes or related to cough measures. <bold>Methods:</bold> RUCC (n=46) and HV (n=19) underwent hypotonic cough challenge, 24h cough monitoring and rs-fMRI (10-min scan, 3T Philips multiband scanner). Data pre-processing, single subject and group ICA were performed (FSL, Oxford UK), followed by dual regression (DR) and covariate analysis. <bold>Results:</bold> RUCC vs. HV were comparable in age (median 62 vs. 56y, p=0.39) and sex distribution (female 59% RUCC vs. 47% HV, p=0.65). DR showed greater rs-fMRI activation within the sensorimotor network in HV compared to RUCC, (p=0.009). In RUCC, rs-fMRI activity was increased in males vs. females in a region of the right frontal lobe (p = 0.01, displayed in Figure). There was no association between rs-CNS signal and cough frequency or maximum cough response to hypotonic saline (no region with p < 0.05). <fig><object-id>erj;64/suppl_68/OA1965/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig><bold>Conclusion</bold> Dysregulated perception and motor control of airway sensations may contribute to RUCC and explain heightened laryngeal symptoms at rest. Frontal lobe CNS activation, associated with cough suppression, may differ between sexes in RUCC.