MisophoniaNCT04348591
Identifying the Optimal Neural Target for Misophonia Interventions
A study testing Cognitive Restructuring and neurostimulation in people with Misophonia and Emotion Dysregulation, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Misophonia, Emotion Dysregulation
- What is being tested?
- Cognitive Restructuring and neurostimulation
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2020to 28 May 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center-Civitan Bldg
Durham, North Carolina, 27710
About this study
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.
Read the 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.
- Conditions
- Misophonia, Emotion Dysregulation
- Being tested
- Cognitive Restructuring, neurostimulation
- Keywords
- neurostimulation, neuroscience, misophonia, emotion dysregulation, insula
- Medical subject headings
- misophonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive RestructuringBehavioural
All participants will learn how to change their thinking in order to be less upset when confronted with stressors
neurostimulationDevice
Also called transcranial magnetic stimulation
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
| Study group | Role | What they receive |
|---|---|---|
| Misophonia Group | Experimental | Participants who endorse Misophonia will undergo a neuroimaging session to identify different neurostimulation targets. Then Misophonic participants will be exposed to aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets. Receives: Behavioral: Cognitive Restructuring; Device: neurostimulation |
| Emotional Dysregulation Clinical Group | Active comparator | Participants who self report high emotional dysregulation and who meet diagnostic criteria for a DSM disorder will undergo a neuroimaging session to identify different neurostimulation targets. Then these participants will be exposed to aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets. Receives: Behavioral: Cognitive Restructuring; Device: neurostimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks
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.
Measured: Two minute blocks during the neurostimulation experimental session during which participants listened to or downregulated emotions associated with experimental sounds (45 minutes total).
Skin Conductance Level (SCL)
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.
Measured: Two minute blocks during the neurostimulation experimental session (when participants listened to or downregulated emotions associated with experimental sounds)
Behavioral Outcome: Acceptability of Procedures
The investigators will record how many participants completed the neurostimulation session as a marker of acceptability.
Measured: At the end of the neurostimulation session (session 3 in the experiment), which occured within a month of the initial assessment
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
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.
Measured: during the neuroimaging session, within a month of the intake assessment
Neuroimaging Outcome: Differential Change in BOLD Signal Within the Ventromedial Prefrontal Cortex (vmPFC) When Engaging in the Regulation of Emotional Versus Misophonic Distress
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.
Measured: during the neuroimaging session, within a month of the intake assessment
Neuroimaging Outcome: Differential Change in BOLD Signal Within the Anterior Insular Cortex (AIC) Activation When Being Presented With Cues for Emotional Versus Misophonic Distress
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.
Measured: during the neuroimaging session, within a month of the intake assessment
Secondary outcomes (7)
Change in Subjective Units of Distress (SUDS)
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.
Measured: Baseline, during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment)
Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS)
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.
Measured: From baseline to the end of neurostimulation session, an average of 4 weeks.
Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile
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.
Measured: At baseline
Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Aversive Versus Neutral Sounds.
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.
Measured: During the neuroimaging session, within a month of the intake assessment
Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Misophonic Versus Aversive Sounds.
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.
Measured: during the neuroimaging session, within a month of the intake assessment
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
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).
Measured: during the neuroimaging session, within a month of the intake assessment
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
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.
Measured: during the neuroimaging session, within a month of the intake assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2020
- Study start28 Oct 2020
- Primary completion27 May 2022
- Study completion28 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MisophoniaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Investigator
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Misophonia Research Fund
- Responsible party
- Sponsor
- Investigators
- Andrada D Neacsiu, PhD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04348591
- Sponsor's protocol ID
- Pro00103863
- Status last verified
- Aug 2023
- First submitted
- 7 Apr 2020
- Last updated
- 25 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Participant data from the study was shared to the Duke Research Data Repository (RDR). Neacsiu, A., LaBar, K., Rosenthal, M. Z., Bukhari-Parlakturk, N., Kelley, L. (2022). Identifying the optimal neural target for misophonia interventions. Duke Research Data Repository. https://doi.org/10.7924/r4ww7jg4k
Publications
Neacsiu AD, Dave S, Gerlus N. The power of context: Enhancing repetitive transcranial magnetic stimulation effects through skillful behavior. Behav Brain Res. 2026 Jun 25;508:116199. doi: 10.1016/j.bbr.2026.116199. Epub 2026 Apr 5.
PubMed 41941945
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identifying the Optimal Neural Target for Misophonia Interventions
- ClinicalTrials.gov ID
- NCT04348591
- Acronym / sponsor ID
- Pro00103863
- Conditions
- Misophonia, Emotion Dysregulation
- Keywords
- neurostimulation, neuroscience, misophonia, emotion dysregulation, insula
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Misophonia Research Fund
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 27 May 2022 (actual)
- Study completion
- 28 May 2022 (actual)
- First posted
- 16 Apr 2020 (actual)
- Results
- Posted 25 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Misophonia Group | Experimental | Behavioral: Cognitive Restructuring, Device: neurostimulationParticipants who endorse Misophonia will undergo a neuroimaging session to identify different neurostimulation targets. Then Misophonic participants will be exposed to aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets. |
| Emotional Dysregulation Clinical Group | Active comparator | Behavioral: Cognitive Restructuring, Device: neurostimulationParticipants who self report high emotional dysregulation and who meet diagnostic criteria for a DSM disorder will undergo a neuroimaging session to identify different neurostimulation targets. Then these participants will be exposed to aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive RestructuringAll participants will learn how to change their thinking in order to be less upset when confronted with stressors | Behavioural | Emotional Dysregulation Clinical Group, Misophonia Group |
| neurostimulationAlso: transcranial magnetic stimulationall 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 | Device | Emotional Dysregulation Clinical Group, Misophonia Group |
Primary outcome
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.
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.
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.
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.
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.
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.
7 secondary outcomes
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)
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.
Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile
Time frame: At baseline
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41941945Neacsiu AD, Dave S, Gerlus N. The power of context: Enhancing repetitive transcranial magnetic stimulation effects through skillful behavior. Behav Brain Res. 2026 Jun 25;508:116199. doi: 10.1016/j.bbr.2026.116199. Epub 2026 Apr 5.
- Individual participant dataSharing planned: Yes. Participant data from the study was shared to the Duke Research Data Repository (RDR). Neacsiu, A., LaBar, K., Rosenthal, M. Z., Bukhari-Parlakturk, N., Kelley, L. (2022). Identifying the optimal neural target for misophonia interventions. Duke Research Data Repository. https://doi.org/10.7924/r4ww7jg4k
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrada D Neacsiu, PhD principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Restructuring and neurostimulation in people with Misophonia and Emotion Dysregulation, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04348591, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2023.