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Misophonia is a disorder of decreased tolerance to certain aversive, repetitive common sounds, or to stimuli associated with these sounds. Two matched groups of adults (29 participants with misophonia and 30 clinical controls with high emotion dysregulation) received inhibitory neurostimulation (1 Hz) over a personalized medial prefrontal cortex (mPFC) target functionally connected to the left insula; excitatory neurostimulation (10 Hz) over a personalized dorsolateral PFC (dlPFC) target; and sham stimulation over either target. Stimulations were applied while participants were either listening or cognitively downregulating emotions associated with personalized aversive, misophonic, or neutral sounds. Subjective units of distress (SUDS) and psychophysiological measurements (e.g., skin conductance response [SCR] and level [SCL]) were collected. Compared to controls, participants with misophonia reported higher distress (∆ SUDS  = 1.91-1.93, ps < 0.001) when listening to and when downregulating misophonic distress. Both types of neurostimulation reduced distress significantly more than sham, with excitatory rTMS providing the most benefit (Cohen's d SUDS  = 0.53; d SCL  = 0.14). Excitatory rTMS also enhanced the regulation of emotions associated with misophonic sounds in both groups when measured by SUDS (d control  = 1.28; d Misophonia  = 0.94), and in the misophonia group alone when measured with SCL (d = 0.20). Both types of neurostimulation were well tolerated. Engaging in cognitive restructuring enhanced with high-frequency neurostimulation led to the lowest misophonic distress, highlighting the best path forward for misophonia interventions., Competing Interests: Declaration of competing interest The authors reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Transdiagnostic clinical emotional dysregulation is a key component of many mental health disorders and offers an avenue to address multiple disorders with one transdiagnostic treatment. In the current study, we pilot an intervention that combines a one-time teaching and practice of cognitive restructuring (CR) with repetitive transcranial magnetic stimulation (rTMS), targeted based on functional magnetic resonance imaging (fMRI)., Methods: Thirty-seven clinical adults who self-reported high emotional dysregulation were enrolled in this randomized, double-blind, placebo-controlled trial. fMRI was collected as participants were reminded of lifetime stressors and asked to downregulate their distress using CR tactics. fMRI BOLD data were analyzed to identify the cluster of voxels within the left dorsolateral prefrontal cortex (dlPFC) with the highest activation when participants attempted to downregulate, versus passively remember, distressing memories. Participants underwent active or sham rTMS (10 Hz) over the left dlPFC target while practicing CR following emotional induction using recent autobiographical stressors., Results: Receiving active versus sham rTMS led to significantly higher high frequency heart rate variability during regulation, lower regulation duration during the intervention, and higher likelihood to use CR during the week following the intervention. There were no differences between conditions when administering neurostimulation alone without the CR skill and compared to sham. Participants in the sham versus active condition experienced less distress the week after the intervention. There were no differences between conditions at the one-month follow up., Conclusion: This study demonstrated that combining active rTMS with emotion regulation training for one session significantly enhances emotion regulation and augments the impact of training for as long as a week. These findings are a promising step towards a combined intervention for transdiagnostic emotion dysregulation., (Copyright © 2022 Elsevier B.V. All rights reserved.)