Increased orbitofrontal connectivity in misophonia

Abstract For individuals with misophonia, specific innocuous sensory stimuli - such as hearing another person chewing or breathing - evoke strong negative emotional and physiological responses, such as extreme anger, disgust, stress and anxiety. Instead people with misophonia do not experience or display atypical reactions to generic aversive sounds such as screams or nails scratching on a blackboard. Misophonia appears to be unrelated to neurological trauma or hearing deficit, and features a characteristic developmental pattern. Its aetiology is currently unknown. The few previous fMRI studies on misophonia showed that sufferers feature increased dorsal anterior insula activity during trigger vs. generic aversive sounds. While this effect likely reflects the saliency associated with the perception of trigger sounds in people with misophonia, in the present fMRI study we investigate the neural mechanisms underlying the emotional reaction to trigger stimuli. To this aim, we probe the task-dependent connectivity of mid-cingulate, medial premotor and ventrolateral premotor cortex. We observe that only in participants with misophonia the presentation of trigger audio-visuals prompts an increased interaction of these three brain regions with the lateral orbitofrontal cortex. This brain region is crucial for behavioural inhibition mediated by cognitive and emotional content (such as in reward-reversal learning) and is part of the temporo-amygdala-orbitofrontal network, which integrates visceral and emotional states with cognition and behaviour. We also observe that in people with misophonia trigger sounds prompt a significant increase in the interaction between mid-cingulate and the primary auditory cortex. Our study replicates previous results and expands the network of brain regions involved in misophonia. The involvement of the orbitofrontal cortex suggests a defective functioning of high-order integrative processes allowing the reappraisal of experience-dependent negative emotional association with harmless sensory stimuli, and sheds light on the mechanisms underlying the compulsive nature of the misophonic reaction. The increased interaction, rather than the overall activity, of the primary auditory cortex with the mid-cingulate supports the hypothesis that the emotional response in misophonia is subserved by an indirect auditory-limbic pathway processing the subjective valence of specific sounds, rather than their physical properties alone.