Structural and Functional Correlates of Higher Cortical Brain Regions in Chronic Refractory Cough

Chronic refractory cough significantly impairs the psychological and social aspects of quality of life. Loss of inhibitory control is suggested as a potential central neurobiological mechanism underlying chronic refractory cough.Do structural and functional changes related to chronic cough occur in higher cortical brain regions?The structural and resting-state functional alterations in the brains of 15 patients with chronic refractory cough and 15 age- and sex-matched healthy control participants were evaluated. Gray matter volumes of the whole brain were measured using voxel-based morphometry based on T1-weighted MRI. Intrinsic functional connectivity within large-scale brain networks was examined on resting-state functional MRI. Correlation analyses were performed to examine the relationships of these brain changes with duration, severity, and impact of cough.Compared with healthy control participants, patients with chronic refractory cough demonstrated a lower gray matter volume in the left frontal cluster and enhanced functional connectivity within the left frontoparietal network, which were associated with greater cough scores. Furthermore, enhanced functional connectivity within the left frontoparietal network was associated with a greater psychological and social impact of coughing. Lower left frontal gray matter volume was associated with longer cough duration.Structural and functional alterations in the left frontal brain regions may be implicated in the psychological and social impact and disease duration of chronic refractory cough. Our findings provide new perspectives on developing interventional approaches targeting the cognitive modulation of chronic coughing.