Skip to main content
OpenTrials
Completed

NCT Number: NCT04348591

Identifying the Optimal Neural Target for Misophonia Interventions

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Misophonia Emotion Dysregulation

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Duke University Medical Center-Civitan Bldg

Durham, North Carolina, 27710, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Interested participants will be excluded if:

  • current or past history of mania or psychosis,
  • verbal IQ < 70,
  • 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),
  • going to jail in the next 2 months,
  • pregnant,
  • high risk for suicide
  • moderate/severe current alcohol or substance dependence,
  • cannot come to Duke for the three study visits.

Inclusion criteria

are:

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

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

Treatment and study plan

cognitive restructuring

Behavioral

All participants will learn how to change their thinking in order to be less upset when confronted with stressors

Neurostimulation

Device

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 names: transcranial magnetic stimulation

Primary outcomes

  1. Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks

    Time frame: Two minute blocks during the neurostimulation experimental session during which participants listened to or downregulated emotions associated with experimental sounds (45 minutes total).

    HF-HRV was extracted from 2 minute blocks during which participants engage in a behavioral strategy (listen or downregulate emotions using cognitive restructuring), while listening to neutral, aversive, and misophonic sounds and receive active or sham neurostimulation. The results represent the average HF-HRV during experimental blocks. The raw values were transformed using a logarithmic function to preserve the normality assumption.

  2. Skin Conductance Level (SCL)

    Time frame: Two minute blocks during the neurostimulation experimental session (when participants listened to or downregulated emotions associated with experimental sounds)

    Physiological arousal measured by SCL during each experimental block was extracted using Acqknowledge software and BIOPAC hardware (during the neurostimulation session). Raw galvanic skin response was continuously collected throughout the experiment. Raw data was then examined for abrupt changes (skin conductance responses), which were removed. The processed data was then averaged for each two minute experimental block. Higher SCL means higher arousal.

  3. Behavioral Outcome: Acceptability of Procedures

    Time frame: At the end of the neurostimulation session (session 3 in the experiment), which occured within a month of the initial assessment

    The investigators will record how many participants completed the neurostimulation session as a marker of acceptability.

  4. 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

    Time frame: during the neuroimaging session, within a month of the intake assessment

    Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. Higher values indicate higher activity changes within a contrast of interes. A dlPFC mask was employed to find the maximum value of the [downregulate misophonic sounds > downregulate aversive sounds] contrast in this region. Once the voxel containing this maximum was identified, a 6 mm sphere ROI was created around this spot (restricted to the dlPFC mask) and the average contrast value within this sphere was used as the outcome variable.

  5. Neuroimaging Outcome: Differential Change in BOLD Signal Within the Ventromedial Prefrontal Cortex (vmPFC) When Engaging in the Regulation of Emotional Versus Misophonic Distress

    Time frame: during the neuroimaging session, within a month of the intake assessment

    Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. A vmPFC mask was employed to find the maximum value of the [downregulate misophonic sounds > downregulate aversive sounds] contrast in this region. Once the voxel containing this maximum was identified, a 6 mm sphere ROI was created around this spot (restricted to the vmPFC mask) and the average contrast value within this sphere will be used as the outcome variable. Higher scores indicate more activity when downregulating misophonic versus aversive sounds.

  6. Neuroimaging Outcome: Differential Change in BOLD Signal Within the Anterior Insular Cortex (AIC) Activation When Being Presented With Cues for Emotional Versus Misophonic Distress

    Time frame: during the neuroimaging session, within a month of the intake assessment

    Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. An AIC mask was employed to find the maximum value of the [hear misophonic sounds > hear aversive sounds] contrast in this region. Once the voxel containing this maximum was identified, a 6 mm sphere ROI was created around this spot (restricted to the AIC mask) and the average contrast value within this sphere will be used as the outcome variable. A larger score indicates more activity when hearing misophonic versus aversive sounds.

Secondary outcomes

  1. Change in Subjective Units of Distress (SUDS)

    Time frame: Baseline, during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment)

    Self reported distress after experimental blocks will also be examined for differences when accounting for baseline distress (during the neurostimulation session). SUDS will be measured using a 0-9 sale, where 0 indicates no distress, and 9 indicates extreme distress. The outcome measure represents SUDS after negative sound presentations (misophonic and aversive) minus SUDS after baseline. Higher SUDS represents higher distress.

  2. Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS)

    Time frame: From baseline to the end of neurostimulation session, an average of 4 weeks.

    A self report assessing difficulties regulating emotions will be examined before and after the experiment (i.e., at the end of the neurostimulation session). The DERS ranges from 36 to 180, with higher scores indicating more dysregulation.

  3. Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile

    Time frame: At baseline

    The PROMIS-43 is a 43-item questionnaire assessing health status in seven domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and participation in social roles. Lower scores indicate less impairment in functioning when compared to higher scores. Each item has five response options ranging in value from 1 to 5, except for the 1 Pain Intensity item which has eleven response options ranging in value from 0 to 10. A raw score is created from each domain that makes up the Profile. Each domain raw score ranging from 6-30 corresponds to a T-Score in the PROMIS scoring manual.

  4. Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Aversive Versus Neutral Sounds.

    Time frame: During the neuroimaging session, within a month of the intake assessment

    Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. The BOLD signal contrast between engaging with aversive sounds and engaging with neutral sounds were compared between groups across the whole brain on a voxel-wise basis. Voxel-wise significant results (i.e., z > 2.3) were clustered to statistically correct for multiple comparisons. The number of significant clusters that emerged from this analysis in each group are presented as outcome.

  5. Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Misophonic Versus Aversive Sounds.

    Time frame: during the neuroimaging session, within a month of the intake assessment

    Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for measuring brain activity using functional magnetic resonance imaging (fMRI). Change in a BOLD signal detected in fMRI, notes changes in brain blood flow and blood oxygenation. Neural activation across the brain when engaging with misophonic sounds versus aversive sounds during the neuroimaging day. The BOLD signal contrast between engaging with misophonic sounds and engaging with aversive sounds were compared between groups across the whole brain on a voxel-wise basis. Voxel-wise significant results (i.e., z > 2.3) were clustered to statistically correct for multiple comparisons. The number of significant clusters that emerged from this analysis in each group are presented as outcome.

  6. 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

    Time frame: during the neuroimaging session, within a month of the intake assessment

    Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. The BOLD signal contrast between regulating versus engaging with misophonic sounds across the entire brain was compared between participant groups on a voxel-wise basis. Voxel-wise results were clustered to statistically correct for multiple comparisons. The number of significant clusters within each group are presented as outcome (more cluster indicates more differences during regulation in that group versus the control group).

  7. 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

    Time frame: during the neuroimaging session, within a month of the intake assessment

    Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. The BOLD signal contrast between regulating and engaging with aversive sounds was compared between participant groups on a voxel-wise basis. Voxel-wise results were clustered to statistically correct for multiple comparisons. The number of significant clusters within each group are reported as the outcome measure.

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

  • Misophonia Research Fund

Registry information

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Apr 16, 2020
Registry last updated
Aug 25, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.