Patterns of shared and differential neural activity in misophonia and non-misophonic clinical emotional dysregulation

Misophonia is a poorly understood clinical condition characterized by reduced tolerance to select trigger sounds. Whether misophonic distress and its regulation involve unique neural mechanisms compared to other forms of emotion dysregulation remains unclear. We used functional magnetic resonance imaging (fMRI) to identify putative neural signatures of misophonic reactivity and regulation compared to a transdiagnostic clinical control group. Twenty-nine adults with misophonia and 30 with high emotional dysregulation and a DSM-5 psychiatric disorder underwent an fMRI session. After the presentation of misophonic, aversive, or neutral sound cues, they either experienced emotions naturally or reduced negative affect through cognitive reappraisal. Compared to controls, participants with misophonia showed greater distress after listening to or downregulating misophonic sounds and lower distress when listening to non-misophonic aversive sounds. Listening to misophonic sounds elicited lower functional connectivity between the right insula and the left dorsomedial prefrontal cortex (dmPFC), and between the left insula and the right superior temporal sulcus, in the misophonia group compared with controls. During the regulation of misophonic sounds, the misophonia group showed increased left insula connectivity with the anterior cingulate cortex and increased right insula connectivity with the bilateral dmPFC and other sensorimotor regions compared to controls. In the misophonia group only, higher emotion dysregulation and lower habitual use of reappraisal were respectively associated with increased insula-dmPFC connectivity and with increased insula connectivity with the dorsolateral prefrontal cortex. Prefrontal cortex activation during regulation of misophonic distress was not significantly different between the two groups. Insula activity and connectivity may be key features that distinguish misophonia from other forms of emotional dysregulation. These novel findings identify candidate neural processes that may be selectively associated with misophonia, as well as processes that may be shared between misophonia and other forms of emotion dysregulation.