Selective Disruption of Salience-Network Anterior Insula Connectivity in Misophonia: A Disorder-Specific Neural Signature.

Misophonia, a disorder characterized by extreme aversion to certain sounds, affects 5%-20% of the general population, yet mechanisms are still largely unknown. Recent neuroimaging studies have reported abnormal functional connectivity of the anterior insula to various limbic, salience, and motor regions in smaller samples of misophonic individuals versus controls, suggesting potential differences in underlying attentional or emotional processes. These findings prompt questions about the insular connectivity profile in larger samples of adults, what patterns emerge when the samples span a wider range of misophonia severity, and how these patterns may or may not overlap with other co-occurring disorders. To address these questions, we analyzed resting-state functional magnetic resonance imaging data from the open Welsh Advanced Neuroimaging Database (N = 162) comprising participants recruited from the general adult population and assessed for sensory sensitivity, anxiety, depression, and autistic traits. A misophonia severity score was derived from the sensory sensitivity data using a model trained on a second adult self-report sample from Oklahoma (N = 777). Using anterior insula as a seed for a whole-brain seed-to-voxel connectivity analysis, the derived misophonia severity scores were found to be significantly related to connectivity from the insula to clusters overlapping the planum temporale, operculum, precentral gyrus, and supplementary motor area. Notably, this insular connectivity profile was unique to the anterior insula of the salience network and was not observed when dividing the sample into misophonia (patient) versus control groups, or when grouping participants as a function of anxiety, depression, or autistic traits. These results underline the importance of the salience-network anterior insula in understanding misophonic aversion and provide tentative evidence of neurological differences between misophonia and anxiety, depression, and autism. This work aids in our understanding of neural mechanisms of misophonia and emphasizes the benefit of treating misophonia as a continuous spectrum disorder to better reflect the variability of symptoms in the real world.