Identifying Optimal Parameters for Neuroscience-Informed Interventions for Misophonia

Background Misophonia is the inability to tolerate certain aversive, repetitive common sounds. Methods Using a within-subjects experimental design, twenty-nine participants with misophonia and thirty clinical controls with high emotion dysregulation received inhibitory neurostimulation (1Hz) over a personalized medial prefrontal cortex (mPFC) target functionally connected to the left insula; excitatory neurostimulation (10Hz) 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 (skin conductance response[SCR] and level [SCL], and high-frequency heart rate variability [HF-HRV]) were collected. Results Compared to controls, participants with misophonia reported higher distress (ΔSUDS = 1.91-1.93, p s<.001) when listening to and when downregulating misophonic distress, although no psychophysiological differences were found. Both types of neurostimulation reduced distress significantly more than sham, with excitatory rTMS providing the most benefit (Cohen’s dSUDS= 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 ( dcontrol = 1.28; dMisophonia= 0.94), and in the misophonia group alone when measured with SCL ( d = 0.20). Both types of neurostimulation were well tolerated and feasible to administer. Discussion Clinical controls and misophonic participants were different in their self-report but not in psychophysiological measures of distress and regulations. Participants reported the lowest misophonic distress when engaging in cognitive restructuring enhanced with high-frequency neurostimulation, a finding that offers insight into the best path forward for misophonia interventions. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04348591 ### Funding Statement This research and the completion of the manuscript were supported by a Misophonia Fund award granted to the first author by the REAM Foundation ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Duke University Health System Institutional Review Board gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors