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| Name | Class |
|---|---|
| Misophonia Research Fund | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cognitive Restructuring | Behavioral | All participants will learn how to change their thinking in order to be less upset when confronted with stressors |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Interested participants will be excluded if:
Inclusion criteria are:
Participants will be matched on gender and age between the two groups
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| Name | Affiliation | Role |
|---|---|---|
| Andrada D Neacsiu, PhD | Duke Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center-Civitan Bldg | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41941945 | Derived | 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. |
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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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Data in SPSS and .csv format along with the data dictionary was submitted and accepted on 10/27/2022. It is available currently at the Duke Research Data Repository (RDR). The Duke RDR provides access to and preservation of the data for a minimum period of 25 years.
Open to any researcher to view and access.
Top reasons for not qualifying included emotion dysregulation & misophonia severity too low; too low severity for misophonic group, but too many misophonic symptoms for control group; moderate/severe current alcohol or substance use disorder; TMS/MRI contraindications; or could not provide usable MRI data.
Participants were recruited through online websites (e.g., Craigslist, Dukelist), social media (Facebook, Instagram, Reddit), flyers, and electronic medical record outreach. Participants reached the study predominantly by seeing advertisements on social media and research websites. Many participants who met the severity cutoff for misophonia also found the study via self-guided internet search.
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| ID | Title | Description |
|---|---|---|
| FG000 | Misophonia Group | Participants who endorse Misophonia will undergo a neuroimaging session to identify different neurostimulation targets. Then Misophonic participants will be exposed to misophonic, aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets. Cognitive Restructuring: All participants will learn how to change their thinking in order to be less upset when confronted with stressors neurostimulation: 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 |
| FG001 | Emotional Dysregulation Clinical Group | 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 misophonic, aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets. Cognitive Restructuring: All participants will learn how to change their thinking in order to be less upset when confronted with stressors neurostimulation: 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
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| Imaging Session (120 Min) |
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| CR Training (45 Min) |
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| Experimental Task (45 Min) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Misophonia Group | 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. Cognitive Restructuring: All participants will learn how to change their thinking in order to be less upset when confronted with stressors neurostimulation: 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 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | lg(ms^2) | Two minute blocks during the neurostimulation experimental session during which participants listened to or downregulated emotions associated with experimental sounds (45 minutes total). |
|
Enrollment through study completion/termination, approximately - 1-2 months.
From intake through study completion, AE/SAEs, distress and risk were assessed as described in the approved DUHS IRB protocol. At the TMS visit, trained study staff queried participants on potential adverse effects that can occur during TMS pre and post TMS- including headache, neck pain, scalp pain, hearing impairment. Most of the AE reported are in relation to neurostimulation visit and only 2 other AEs, not connected to the neurostimulation visit were reported in the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Misophonia Group | 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. Cognitive Restructuring: All participants will learn how to change their thinking in order to be less upset when confronted with stressors neurostimulation: 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment | mild |
Several protocol deviations were engaged in to accommodate participants in the study including adjusting the targeting protocol in 5 cases, imputing SUDS trial baseline values if they were left blank by participants (using the session baseline SUDS values), and adjusting intensity of stimulation for participants who found it too uncomfortable at the targeted dose.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Andrada D. Neacsiu | Duke University | 919-684-6714 | andrada.neacsiu@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 28, 2023 | Mar 28, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 4, 2022 | Mar 29, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| C000719531 | misophonia |
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| ID | Term |
|---|---|
| D000088686 | Cognitive Restructuring |
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D015928 | Cognitive Behavioral Therapy |
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
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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
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All participants will undergo different types of neurostimulation to probe different areas of the emotion regulation and misophonic networks while being exposed to sounds. One of these neurostimulation blocks will involve sham (inactive) neurostimulation. The investigator and the participants will be blind to which block has active and which block has sham neurostimulation
| 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 |
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| 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. | 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. | during the neuroimaging session, within a month of the intake assessment |
| 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. | 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. | 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. | 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. | 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). | 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. | during the neuroimaging session, within a month of the intake assessment |
| Withdrawal by Subject |
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| NOT COMPLETED |
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| Completed HF rTMS Over the Right dlPFC Experimental Condition | Each participant listened to neutral, aversive, and misophonic trigger sounds that were personalized while receiving high frequency neurostimulation over the right dlPFC |
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| Completed LF rTMS Over the Right mPFC Experimental Condition | Each participant listened to neutral, aversive, and misophonic trigger sounds that were personalized while receiving low frequency neurostimulation over the right mPFC |
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| COMPLETED |
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| NOT COMPLETED |
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| BG001 | Emotional Dysregulation Clinical Group | 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. Cognitive Restructuring: All participants will learn how to change their thinking in order to be less upset when confronted with stressors neurostimulation: 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 |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| misophonia questionnaire Subscale 1 | Trigger Subscale 1 of the misophonia questionnaire includes 8 triggers that participants rate they are sensitive to on a scale of 0 to 4 where 0=Not at all true to 4=Always True. A total subscale score is computed by averaging the items (range 0-4). Higher score indicates higher misophonia sensitivity (i.e., more severity). | Mean | Standard Deviation | units on a scale |
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| misophonia questionnaire Subscale 2 | Response Subscale 2 of the Misophonia questionnaire has 11 potential statements that participants rate occur when triggered on a scale of 0 to 4 where 0=Never to 4=Always. A total subscale score is computed by averaging the scores on these items. Higher scores indicate more misophonia severity. | Mean | Standard Deviation | units on a scale |
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| misophonia questionnaire severity | 1 question where participants rate the severity of their sound sensitivity from 1=minimal to 15=very severe. | Mean | Standard Deviation | units on a scale |
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| Difficulties in emotion regulation scale | Difficulties with emotion regulation statements were rated on frequency on a scale of 1 to 5 where 1=Almost Never and 5=Almost Always. After collecting the ratings, in scoring some of the items on the scale are reverse scored. Next, a score is computed by adding all the items on the scale, yielding a total score that ranges from 36 to 180. Higher scores indicate more difficulties with emotional dysregulation. | Mean | Standard Deviation | units on a scale |
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| OG001 | Emotional Dysregulation Clinical Group | 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. Cognitive Restructuring: All participants will learn how to change their thinking in order to be less upset when confronted with stressors neurostimulation: 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 |
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| Primary | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | microsemens | Two minute blocks during the neurostimulation experimental session (when participants listened to or downregulated emotions associated with experimental sounds) |
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| Primary | Behavioral Outcome: Acceptability of Procedures | The investigators will record how many participants completed the neurostimulation session as a marker of acceptability. | Participants who completed the study | Posted | Count of Participants | Participants | At the end of the neurostimulation session (session 3 in the experiment), which occured within a month of the initial assessment |
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| Primary | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | BOLD arbitrary units | during the neuroimaging session, within a month of the intake assessment |
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| Primary | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | BOLD arbitrary units | during the neuroimaging session, within a month of the intake assessment |
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| Primary | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | BOLD arbitrary units | during the neuroimaging session, within a month of the intake assessment |
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| Secondary | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | units on a scale | Baseline, during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment) |
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| Secondary | 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. | Some participants dropped out or were lost to contact by follow up. | Posted | Mean | Standard Deviation | score on a scale | From baseline to the end of neurostimulation session, an average of 4 weeks. |
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| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | At baseline |
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| Secondary | 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. | Posted | Number | clusters where differences emerged | During the neuroimaging session, within a month of the intake assessment |
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| Secondary | 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. | Posted | Number | clusters | during the neuroimaging session, within a month of the intake assessment |
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| Secondary | 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). | Posted | Number | clusters | during the neuroimaging session, within a month of the intake assessment |
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| Secondary | 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. | Posted | Number | clusters | during the neuroimaging session, within a month of the intake assessment |
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| 0 |
| 27 |
| 0 |
| 27 |
| 8 |
| 27 |
| EG001 | Emotional Dysregulation Clinical Group | 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. Cognitive Restructuring: All participants will learn how to change their thinking in order to be less upset when confronted with stressors neurostimulation: 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 | 0 | 27 | 0 | 27 | 4 | 27 |
| Scalp Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | mild |
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| Pain | Nervous system disorders | Non-systematic Assessment | localized pain at site of TMS |
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| Skin discomfort | Skin and subcutaneous tissue disorders | Non-systematic Assessment | at site of TMS neurostimulation |
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| Eye Pain | Nervous system disorders | Non-systematic Assessment | Pain in eye that was mild which may be due to TMS frontal target engaged a nerve connected to eye. |
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| COVID | Infections and infestations | Non-systematic Assessment |
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| Irritability | Psychiatric disorders | Non-systematic Assessment | noise of the MRI machine made participant irritated. |
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Not provided
Not provided
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
| listen to neutral sounds + HF rTMS |
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| listen to neutral sounds + LF rTMS |
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| listen to aversive sounds + sham stimulation |
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| listen to aversive sounds + HF rTMS |
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| listen to aversive sounds + LF rTMS |
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| listen to misophonic sounds + sham stimulation |
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| listen to misophonic sounds + HF rTMS |
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| listen to misophonic sounds + LF rTMS |
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| downregulate distress associated with aversive sounds+ sham stimulation |
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| downregulate distress associated with aversive sounds+ HF rTMS |
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| downregulate distress associated with aversive sounds+ LF rTMS |
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| downregulate distress associated with misophonic sounds+ sham stimulation |
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| downregulate distress associated with misophonic sounds+ HF rTMS |
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| downregulate distress associated with misophonic sounds+ LF rtMS |
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| A MMANOVA analysis using an unstructured covariance structure examined changes in SCL between groups, experimental types of neurostimulation, and their interaction, controlling for baseline, racial background, coil to cortex distance, and headache | Mixed Models Analysis | This is the main effect of neurostimulation condition. Specifically here we show the difference in estimated marginal means between sham and HF-rTMS | .001 | Mean Difference (Final Values) | .493 | Standard Error of the Mean | .148 | 2-Sided | 95 | .198 | .787 | Superiority |
| A MMANOVA analysis using an unstructured covariance structure examined changes in SCL between groups, experimental types of neurostimulation, and their interaction, controlling for baseline, racial background, coil to cortex distance, and headache | Mixed Models Analysis | This is the main effect of neurostimulation administered, specifically comparing estimated marginal means for sham and LF-rTMS | .002 | Mean Difference (Final Values) | .469 | Standard Error of the Mean | .144 | 2-Sided | 95 | .182 | .757 | Superiority |
| The investigators tested the interaction between experimental neurostimulation (sham, active high frequency rTMS, active low frequency rTMS), instruction provided (listen to neutral sound; listen to aversive sound, listen to misophonic sound, downregulate aversive sound, downregulate misophonic sound), and group (misophonic, clinical control) as part of the same MMANOVA analysis described above (i.e., controlling for coil-to-cortex distance, racial background, baseline, & presence of headache). | Mixed Models Analysis | .0005 | Mean Difference (Final Values) | 0.73 | 2-Sided | mean difference between sham and HF-rTMS for misophonia participants only when downregulating misophonic sounds | Superiority |
| listen to neutral sounds + HF rTMS |
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| listen to neutral sounds + LF rTMS |
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| listen to aversive sounds + sham stimulation |
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| listen to aversive sounds + HF rTMS |
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| listen to aversive sounds + LF rTMS |
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| listen to misophonic sounds + sham stimulation |
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| listen to misophonic sounds+ HF rTMS |
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| listen to misophonic sounds + LF rTMS |
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| downregulate distress associated with aversive sounds+ sham stimulation |
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| downregulate distress associated with aversive sounds+ HF rTMS |
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| downregulate distress associated with aversive sounds+ LF rTMS |
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| downregulate distress associated with misophonic sounds+ sham stimulation |
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| downregulate distress associated with misophonic sounds+ HF rTMS |
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| downregulate distress associated with misophonic sounds+ LF rTMS |
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| The MMANOVA analysis of SUDS used a Toeplitz covariance structure. This analysis presents the main effect of neurostimulation experimental condition. The outcome variable was the difference between SUDS after each sound presentation and baseline, controlling for racial background, headache, and coil to cortex difference. Two participants were excluded from this analysis, one in each condition, because they provided outlier data. | Mixed Models Analysis | <.0000001 | This p-value corresponds to the difference between sham and HF-rTMS stimulation | Mean Difference (Final Values) | .909 | Standard Error of the Mean | .147 | 2-Sided | 95 | .62 | 1.97 | Superiority |
| The MMANOVA analysis of SUDS used a Toeplitz covariance structure. This analysis presents the main effect of neurostimulation experimental condition. The outcome variable was the difference between SUDS after each sound presentation and baseline, controlling for racial background, headache, and coil to cortex difference. Two participants were excluded from this analysis, one in each condition, because they provided outlier data. | Mixed Models Analysis | .018 | The test corresponds to the difference between sham and LF-rTMS | Mean Difference (Final Values) | .331 | Standard Error of the Mean | .139 | 2-Sided | 95 | .057 | .605 | Superiority |
| The MMANOVA analysis of SUDS used a Toeplitz covariance structure. This analysis presents the interaction effect of group by neurostimulation experimental condition. The outcome variable was the difference between SUDS after each sound presentation and baseline, controlling for racial background, headache, and coil to cortex difference. Two participants were excluded from this analysis, one in each condition, because they provided outlier data. | Mixed Models Analysis | <.000001 | Mean Difference (Final Values) | 1.02 | 2-Sided | For participants with misophonia difference in distress produced by a misophonic sound when downregulating misophonic sounds while receiving sham vs.HF-rTMS | Superiority |
| End of neurostimulation session |
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Repeated measures ANOVA (controlling for racial background) |
| ANCOVA |
This analysis corresponds to the main effect of group. |
| >.012 |
| Superiority |
| P43-Fatigue |
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| P43- Sleep disturbance |
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| P43- Ability to partake in social roles |
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| P43-Pain interference |
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| P43-Physical functioning |
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| t-test, 2 sided |
| .29 |
| Superiority |
| An independent samples t-test was conducted to examine between group differences at the intake assessment on the PROMIS Fatigue subscale | t-test, 2 sided | .64 | Superiority |
| An independent samples t-test was conducted to examine between group differences at the intake assessment on the PROMIS Sleep disturbance subscale | t-test, 2 sided | .16 | Superiority |
| An independent samples t-test was conducted to examine between group differences at the intake assessment on the PROMIS Ability to partake in social roles subscale | t-test, 2 sided | .56 | Superiority |