Clinical trial NCT04348591: Identifying the Optimal Neural Target for Misophonia Interventions
Official title: Identifying the Optimal Neural Target for Misophonia Interventions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Misophonia
Emotion Dysregulation
Keywords: neurostimulation
neuroscience
misophonia
emotion dysregulation
insula
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Misophonia Research Fund
First posted: 2020-04-16
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Interested participants will be excluded if:

1. current or past history of mania or psychosis,
2. verbal IQ \< 70,
3. not medically cleared for TMS or fMRI (for example taking medications known to reduce the seizure threshold such as Lamictal, Lithium, Clozaril, stimulants including the ADHD medications (e.g. Ritalin, Adderall), Wellbutrin/Buproprion, Provigil (Modafinil), Aminophylline, and Theophylline, implants, TBI, stroke, etc),
4. going to jail in the next 2 months,
5. pregnant,
6. high risk for suicide
7. moderate/severe current alcohol or substance dependence,
8. cannot come to Duke for the three study visits.

Inclusion criteria are:

1. stable psychotherapy and medication for at least 4 weeks
2. self reports high emotional dysregulation OR misophonia

Participants will be matched on gender and age between the two groups

Primary outcomes:
measure: Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks
timeFrame: Two minute blocks during the neurostimulation experimental session during which participants listened to or downregulated emotions associated with experimental sounds (45 minutes total).
measure: Skin Conductance Level (SCL)
timeFrame: Two minute blocks during the neurostimulation experimental session (when participants listened to or downregulated emotions associated with experimental sounds)
measure: Behavioral Outcome: Acceptability of Procedures
timeFrame: At the end of the neurostimulation session (session 3 in the experiment), which occured within a month of the initial assessment
measure: Neuroimaging Outcome: Differential Change in BOLD Signal Between Groups Within the Dorsolateral Prefrontal Cortex (dlPFC), That is Greater During Regulation of Misophonic Versus Non-misophonic Distress
timeFrame: during the neuroimaging session, within a month of the intake assessment
measure: Neuroimaging Outcome: Differential Change in BOLD Signal Within the Ventromedial Prefrontal Cortex (vmPFC) When Engaging in the Regulation of Emotional Versus Misophonic Distress
timeFrame: during the neuroimaging session, within a month of the intake assessment
measure: Neuroimaging Outcome: Differential Change in BOLD Signal Within the Anterior Insular Cortex (AIC) Activation When Being Presented With Cues for Emotional Versus Misophonic Distress
timeFrame: during the neuroimaging session, within a month of the intake assessment
Secondary outcomes:
measure: Change in Subjective Units of Distress (SUDS)
timeFrame: Baseline, during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment)
measure: Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS)
timeFrame: From baseline to the end of neurostimulation session, an average of 4 weeks.
measure: Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile
timeFrame: At baseline
measure: Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Aversive Versus Neutral Sounds.
timeFrame: During the neuroimaging session, within a month of the intake assessment
measure: Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Misophonic Versus Aversive Sounds.
timeFrame: during the neuroimaging session, within a month of the intake assessment
measure: Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Downregulation of Distress Associated With Misophonic Sounds to Exposure to Misophonic Sounds
timeFrame: during the neuroimaging session, within a month of the intake assessment
measure: Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Downregulation of Distress Associated With Aversive Sounds to Exposure to AversiveSounds
timeFrame: during the neuroimaging session, within a month of the intake assessment
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center-Civitan Bldg
state: North Carolina
Study officials:
affiliation: Duke Health
name: Andrada D Neacsiu, PhD
role: PRINCIPAL_INVESTIGATOR
References: