Global and local brain connectivity changes associated with sudden unilateral sensorineural hearing loss

Recent studies suggest that even moderate sudden sensorineural hearing loss (SSNHL) causes reduction of gray matter volume in the primary auditory cortex, diminishing its ability to react to sound stimulation, as well as reorganization of functional brain networks. We employed resting-state functional MRI (rs-fMRI), in conjunction with graph-theoretical analysis and a newly developed functional "disruption index," to study whole-brain as well as local functional changes in patients with unilateral SSNHL. We also assessed the potential of graph-theoretical measures as biomarkers of disease, in terms of their relationship to clinically relevant audiological parameters. Eight patients with moderate or severe unilateral SSNHL and 15 healthy controls were included in this prospective pilot study. All patients underwent rs-fMRI to study potential changes in brain connectivity. From rs-fMRI data, global and local graph-theoretical measures, disruption index, and audiological examinations were estimated. Mann-Whitney U tests were used to study the differences between SSNHL patients and healthy controls. Associations between brain metrics and clinical variables were studied using multiple linear regressions, and the presence or absence of brain network hubs was assessed using Fisher's exact test. No statistically significant differences between SSNHL patients and healthy controls were found in global or local network measures. However, when analyzing brain networks through the disruption index, we found a brain-wide functional network reorganization (p < 0.001 as compared with controls), whose extent was associated with clinical impairment (p < 0.05). We also observed several functional hubs in SSNHL patients that were not present in healthy controls and vice versa. Our results demonstrate a brain involvement in SSNHL patients, not detectable using conventional graph-theoretical analysis, which may yield subtle disease clues and possibly aid in monitoring disease progression in clinical trials.