[Brain activity alterations in chronic cough: a resting-state functional magnetic resonance imaging study]

Objective: To explore the characteristics of altered brain functional activity in patients with chronic cough using resting-state functional magnetic resonance imaging (fMRI). Methods: This was a prospective study. From January 2016 to January 2019, a total of 20 patients with refractory chronic cough [10 males and 10 females, (39.3±8.2) years], 19 patients with somatic cough syndrome [14 males and 5 females, (34.5±9.2) years], and 29 healthy controls [19 males and 10 females, (38.3±12.1) years] were recruited from the chronic cough outpatient clinic of the First Affiliated Hospital of Guangzhou Medical University for analysis. All participants underwent resting-state fMRI, as well as assessment of cough severity, and capsaicin cough challenge. The amplitude of low-frequency fluctuations (ALFF) was used to assess brain functional activity. First, differences in brain activity between patients with refractory chronic cough and healthy controls were compared. Subsequently, brain regions showing significant differences were selected as seed points, and seed-based whole-brain functional connectivity (FC) analyses were performed to examine group differences. Cough severity was evaluated using the visual analog scale (VAS), and cough sensitivity was defined as the capsaicin concentration that elicited five coughs (C5), expressed as lgC5. One-way analysis of variance (ANOVA) was used to compare the differences in lung function among groups. The Kruskal-Wallis test was applied to compare the differences in cough symptom scores (VAS) and capsaicin cough sensitivity (lgC5) among groups. The fMRI data were statistically analyzed using Rest 1.8 software, and two independent-sample t-tests were conducted for each group. Results: Patients with refractory chronic cough exhibited significantly higher ALFF values in the right cerebellar region 8 (0.96±0.14 vs. 0.72±0.15, t=5.46, P<0.001) and the right cerebellar region Crus2 (0.87±0.11 vs. 0.68±0.11, t=6.25, P<0.001) than healthy controls. Patients with somatic cough syndrome had significantly higher ALFF values in the rectus frontal muscle than healthy controls (1.19±0.26 vs. 0.90±0.16, t=4.92, P<0.001). With the right cerebellar region 8 as the seed point, the analysis of the whole brain FC showed that patients with refractory chronic cough had higher FC values in the left cerebellar region 8 (0.60±0.18 vs. 0.35±0.15, t=5.47, P<0.001), cerebellar vermis (0.85±0.17 vs. 0.69±0.16, t=5.26, P<0.001), and claustrum (0.33±0.13 vs. 0.14±0.10, t=6.02, P<0.001). With the right cerebellar region Crus2 as the seed point, the analysis of the whole brain FC showed that patients with refractory chronic had higher FC values in the right middle temporal gyrus, thalamus (0.31±0.17 vs. 0.10±0.11, t=5.57, P<0.001), right dorsolateral superior frontal gyrus (0.35±0.16 vs. 0.1±0.13, t=6.20, P<0.001) and right posterior central gyrus (0.41±0.19 vs. 0.17±0.17, t=4.52, P<0.001). In the correlation analysis, there was a moderate positive correlation (r=0.57, P=0.001) between the ALFF values of the right cerebellar region 8 and Crus2 regions in patients with refractory chronic cough. Conclusions: Enhanced FC in multiple brain regions was found in patients with refractory chronic cough and patients with somatic cough syndrome, suggesting central sensitization in these patients. The different active brain regions in patients with refractory chronic cough and patients with somatic cough syndrome indicate different central hypersensitivity mechanisms among different causes of chronic cough.