Identifying the Optimal Neural Target for Misophonia Interventions
Condition: Misophonia; Emotion Dysregulation
Study type: Interventional

Summary: 
      Misophonia, the inability to tolerate certain repetitive aversive sounds that are common, is
      gaining recognition as a debilitating condition. It is not a well-understood condition and
      there are no known treatments. Up to one in five people report moderate or higher misophonia
      symptoms; nevertheless, resources aimed at understanding and treating this problem are
      scarce. In order to align misophonia research with the priorities of large funding agencies
      such as the National Institute of Mental Health, the investigators propose a novel study
      aimed at separating misophonic distress from other types of emotional distress. The
      investigators plan to examine changes in brain activation during presentation and regulation
      of misophonic versus distressing sounds. Emergent neural networks that may be involved in
      misophonia will then be tested in the lab with the use of noninvasive neurostimulation, a
      novel tool that can enhance or inhibit activation in a targeted brain region. The
      investigators plan to modulate activation in key areas of the misophonia brain circuitry with
      the aim to identify the optimal neural target for misophonia interventions. Our
      multidisciplinary team at the Duke Center for Misophonia and Emotion Regulation brings
      together experts in misophonia, neuroscience, neuromodulation, neurology, and biostatistics
      who share the long-term goal of developing and refining an intervention for this condition in
      an environment that is optimal to conduct the proposed research.

      The investigators propose to recruit adults who self-report significant misophonia symptoms
      and adults who meet criteria for a current psychiatric disorder and who self-report
      difficulties calming down when upset. All participants will undergo a brain imaging session
      during which misophonic cues; distressing, non-misophonic cues; or neutral cues will be
      presented. Participants will then be asked to experience, or attempt to downregulate emotions
      associated with these cues. Based on the imaging results, two personalized neurostimulation
      targets will be identified: (1) the region in the frontal cortex with the most activity
      during the downregulation of misophonic versus neutral sounds and (2) the prefrontal region
      with the strongest functional connectivity to the anterior insular cortex. Participants will
      receive real or sham neurostimulation over the prefrontal cortex and insula in a random
      order, while engaging in listening to versus downregulating misophonic, aversive, or neutral
      cues. The investigators plan to assess emotional dysregulation, psychopathology, and
      misophonia with a multi-method battery of measures during all three study appointments.
      Feasibility and acceptability will be examined qualitatively. If successful, our study can be
      the first step in a series of investigations that establish the unique targets for neural
      intervention for misophonia.
    

Detailed description: 
      Consistent with NIMH strategic priorities, neural targets that account for individual
      differences are needed for the next generation of mental health interventions. Misophonia,
      the inability to tolerate certain aversive repetitive and common sounds, is gaining rapid
      recognition as a debilitating condition that is not currently well understood and for which
      interventions do not yet exist. In order to align research efforts to understand and treat
      misophonia with NIMH priorities, the investigators propose to conduct an experimental study
      that differentiates the neural circuitry of misophonia-induced distress from other types of
      emotional distress, and that begins to identify the optimal neural target for possible
      interventions. Noninvasive neurostimulation (i.e., the purposeful modulation of neural
      circuitry), such as repetitive transcranial magnetic stimulation (rTMS), is a powerful tool
      which can modulate neuronal activation and can be used to examine the responsiveness of
      neural circuits to intervention. Therefore, for this project, the investigators bring
      together a multidisciplinary team of researchers with expertise in misophonia, neuroscience,
      neuromodulation, biostatistics, and neurology with the aims to: (1) differentiate the brain
      circuitry dysfunction in misophonia compared to non-misophonia emotional distress and (2)
      identify the optimal intervention target for changing misophonic distress using rTMS. The
      investigators propose to recruit adults who self-report significant misophonia symptoms and a
      comparison group of adults who meet criteria for a current psychiatric disorder and who
      self-report high emotional dysregulation. Those who have contra-indications for MRI or rTMS
      will be excluded. All participants will undergo an MRI session during which misophonic cues;
      aversive, non-misophonic cues; or neutral cues will be presented. Participants will be asked
      to listen only or listen and attempt to downregulate emotions associated with these cues.
      Functional MRI (fMRI) analysis will then be performed to define two personalized
      neurostimulation targets defined as the region in the frontal cortex that is the most (1)
      activated during emotion regulation and (2) connected to the anterior insular cortex (AIC)
      during emotional experiencing. Participants will be assigned to receive active or sham
      neurostimulation over target 1 and target 2 in a random order, while engaged in listening to
      versus downregulating misophonic, aversive, or neutral cues. The investigators plan to employ
      excitatory neuromodulation to examine the effects of enhancing prefrontal cortex activation
      during emotion regulation. The investigators also plan to employ inhibitory neuromodulation
      to examine the effects of inhibiting AIC activation during listening only without efforts to
      regulate emotional distress. The investigators plan to assess emotional dysregulation,
      psychopathology, and misophonia with a multi-method battery of measures during all three
      study appointments. Feasibility and acceptability will be examined qualitatively. The
      investigators will use results from this study to design larger trials and to seek federal
      funding with the ultimate goal of designing an effective misophonia intervention. If
      successful, our study can be the first step in a series of investigations that establish the
      unique targets for neural intervention for misophonia.
    

Intervention name(s): Cognitive Restructuring; neurostimulation
Intervention type(s): Behavioral; Device
Intervention description(s): All participants will learn how to change their thinking in order to be less upset when confronted with stressors; all participants will receive inhibitory, excitatory, and sham transcranial magnetic stimulation over different neural targets during the experimental session. The purpose of the neurostimulation is not treatment, but causal interference/enhancing of brain circuitry to identify candidate neural regions for future interventions
Other intervention name(s): transcranial magnetic stimulation
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: The investigators plan to compare adults who report misophonia with adults who report clinical emotional dysregulation in their neurobiological response to misophonic, aversive, and neutral sounds
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: neurostimulation; neuroscience; misophonia; emotion dysregulation; insula