Misophonia, Emotion Dysregulation
Conditions
Keywords
neurostimulation, neuroscience, misophonia, emotion dysregulation, insula
Brief summary
Misophonia, the inability to tolerate certain repetitive aversive sounds that are common, is gaining recognition as a debilitating condition. It is not a well-understood condition and there are no known treatments. Up to one in five people report moderate or higher misophonia symptoms; nevertheless, resources aimed at understanding and treating this problem are scarce. In order to align misophonia research with the priorities of large funding agencies such as the National Institute of Mental Health, the investigators propose a novel study aimed at separating misophonic distress from other types of emotional distress. The investigators plan to examine changes in brain activation during presentation and regulation of misophonic versus distressing sounds. Emergent neural networks that may be involved in misophonia will then be tested in the lab with the use of noninvasive neurostimulation, a novel tool that can enhance or inhibit activation in a targeted brain region. The investigators plan to modulate activation in key areas of the misophonia brain circuitry with the aim to identify the optimal neural target for misophonia interventions. Our multidisciplinary team at the Duke Center for Misophonia and Emotion Regulation brings together experts in misophonia, neuroscience, neuromodulation, neurology, and biostatistics who share the long-term goal of developing and refining an intervention for this condition in an environment that is optimal to conduct the proposed research. The investigators propose to recruit adults who self-report significant misophonia symptoms and adults who meet criteria for a current psychiatric disorder and who self-report difficulties calming down when upset. All participants will undergo a brain imaging session during which misophonic cues; distressing, non-misophonic cues; or neutral cues will be presented. Participants will then be asked to experience, or attempt to downregulate emotions associated with these cues. Based on the imaging results, two personalized neurostimulation targets will be identified: (1) the region in the frontal cortex with the most activity during the downregulation of misophonic versus neutral sounds and (2) the prefrontal region with the strongest functional connectivity to the anterior insular cortex. Participants will receive real or sham neurostimulation over the prefrontal cortex and insula in a random order, while engaging in listening to versus downregulating misophonic, aversive, or neutral cues. The investigators plan to assess emotional dysregulation, psychopathology, and misophonia with a multi-method battery of measures during all three study appointments. Feasibility and acceptability will be examined qualitatively. If successful, our study can be the first step in a series of investigations that establish the unique targets for neural intervention for misophonia.
Detailed description
Consistent with NIMH strategic priorities, neural targets that account for individual differences are needed for the next generation of mental health interventions. Misophonia, the inability to tolerate certain aversive repetitive and common sounds, is gaining rapid recognition as a debilitating condition that is not currently well understood and for which interventions do not yet exist. In order to align research efforts to understand and treat misophonia with NIMH priorities, the investigators propose to conduct an experimental study that differentiates the neural circuitry of misophonia-induced distress from other types of emotional distress, and that begins to identify the optimal neural target for possible interventions. Noninvasive neurostimulation (i.e., the purposeful modulation of neural circuitry), such as repetitive transcranial magnetic stimulation (rTMS), is a powerful tool which can modulate neuronal activation and can be used to examine the responsiveness of neural circuits to intervention. Therefore, for this project, the investigators bring together a multidisciplinary team of researchers with expertise in misophonia, neuroscience, neuromodulation, biostatistics, and neurology with the aims to: (1) differentiate the brain circuitry dysfunction in misophonia compared to non-misophonia emotional distress and (2) identify the optimal intervention target for changing misophonic distress using rTMS. The investigators propose to recruit adults who self-report significant misophonia symptoms and a comparison group of adults who meet criteria for a current psychiatric disorder and who self-report high emotional dysregulation. Those who have contra-indications for MRI or rTMS will be excluded. All participants will undergo an MRI session during which misophonic cues; aversive, non-misophonic cues; or neutral cues will be presented. Participants will be asked to listen only or listen and attempt to downregulate emotions associated with these cues. Functional MRI (fMRI) analysis will then be performed to define two personalized neurostimulation targets defined as the region in the frontal cortex that is the most (1) activated during emotion regulation and (2) connected to the anterior insular cortex (AIC) during emotional experiencing. Participants will be assigned to receive active or sham neurostimulation over target 1 and target 2 in a random order, while engaged in listening to versus downregulating misophonic, aversive, or neutral cues. The investigators plan to employ excitatory neuromodulation to examine the effects of enhancing prefrontal cortex activation during emotion regulation. The investigators also plan to employ inhibitory neuromodulation to examine the effects of inhibiting AIC activation during listening only without efforts to regulate emotional distress. The investigators plan to assess emotional dysregulation, psychopathology, and misophonia with a multi-method battery of measures during all three study appointments. Feasibility and acceptability will be examined qualitatively. The investigators will use results from this study to design larger trials and to seek federal funding with the ultimate goal of designing an effective misophonia intervention. If successful, our study can be the first step in a series of investigations that establish the unique targets for neural intervention for misophonia.
Interventions
BEHAVIORALCognitive Restructuring
All participants will learn how to change their thinking in order to be less upset when confronted with stressors
DEVICEneurostimulation
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
Sponsors
Misophonia Research Fund
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
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
Intervention model description
The investigators plan to compare adults who report misophonia with adults who report clinical emotional dysregulation in their neurobiological response to misophonic, aversive, and neutral sounds
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Interested participants will be excluded if: 1. current or past history of mania or psychosis, 2. verbal IQ \< 70, 3. not medically cleared for TMS or fMRI (for example taking medications known to reduce the seizure threshold such as Lamictal, Lithium, Clozaril, stimulants including the ADHD medications (e.g. Ritalin, Adderall), Wellbutrin/Buproprion, Provigil (Modafinil), Aminophylline, and Theophylline, implants, TBI, stroke, etc), 4. going to jail in the next 2 months, 5. pregnant, 6. high risk for suicide 7. moderate/severe current alcohol or substance dependence, 8. cannot come to Duke for the three study visits. Inclusion criteria are: 1. stable psychotherapy and medication for at least 4 weeks 2. self reports high emotional dysregulation OR misophonia Participants will be matched on gender and age between the two groups
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skin Conductance Level (SCL) | 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. |
| Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | 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. |
| Behavioral Outcome: Acceptability of Procedures | 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 | 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 | 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 | during the neuroimaging session, within a month of the intake assessment | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. An AIC mask was employed to find the maximum value of the \[hear misophonic sounds \> hear aversive sounds\] contrast in this region. Once the voxel containing this maximum was identified, a 6 mm sphere ROI was created around this spot (restricted to the AIC mask) and the average contrast value within this sphere will be used as the outcome variable. A larger score indicates more activity when hearing misophonic versus aversive sounds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subjective Units of Distress (SUDS) | Baseline, during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment) | Self reported distress after experimental blocks will also be examined for differences when accounting for baseline distress (during the neurostimulation session). SUDS will be measured using a 0-9 sale, where 0 indicates no distress, and 9 indicates extreme distress. The outcome measure represents SUDS after negative sound presentations (misophonic and aversive) minus SUDS after baseline. Higher SUDS represents higher distress. |
| Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS) | From baseline to the end of neurostimulation session, an average of 4 weeks. | A self report assessing difficulties regulating emotions will be examined before and after the experiment (i.e., at the end of the neurostimulation session). The DERS ranges from 36 to 180, with higher scores indicating more dysregulation. |
| Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | At baseline | The PROMIS-43 is a 43-item questionnaire assessing health status in seven domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and participation in social roles. Lower scores indicate less impairment in functioning when compared to higher scores. Each item has five response options ranging in value from 1 to 5, except for the 1 Pain Intensity item which has eleven response options ranging in value from 0 to 10. A raw score is created from each domain that makes up the Profile. Each domain raw score ranging from 6-30 corresponds to a T-Score in the PROMIS scoring manual. |
| Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Aversive Versus Neutral Sounds. | During the neuroimaging session, within a month of the intake assessment | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. The BOLD signal contrast between engaging with aversive sounds and engaging with neutral sounds were compared between groups across the whole brain on a voxel-wise basis. Voxel-wise significant results (i.e., z \> 2.3) were clustered to statistically correct for multiple comparisons. The number of significant clusters that emerged from this analysis in each group are presented as outcome. |
| Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Misophonic Versus Aversive Sounds. | during the neuroimaging session, within a month of the intake assessment | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for measuring brain activity using functional magnetic resonance imaging (fMRI). Change in a BOLD signal detected in fMRI, notes changes in brain blood flow and blood oxygenation. Neural activation across the brain when engaging with misophonic sounds versus aversive sounds during the neuroimaging day. The BOLD signal contrast between engaging with misophonic sounds and engaging with aversive sounds were compared between groups across the whole brain on a voxel-wise basis. Voxel-wise significant results (i.e., z \> 2.3) were clustered to statistically correct for multiple comparisons. The number of significant clusters that emerged from this analysis in each group are presented as outcome. |
| 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 | during the neuroimaging session, within a month of the intake assessment | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. The BOLD signal contrast between regulating versus engaging with misophonic sounds across the entire brain was compared between participant groups on a voxel-wise basis. Voxel-wise results were clustered to statistically correct for multiple comparisons. The number of significant clusters within each group are presented as outcome (more cluster indicates more differences during regulation in that group versus the control group). |
| 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 | during the neuroimaging session, within a month of the intake assessment | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. The BOLD signal contrast between regulating and engaging with aversive sounds was compared between participant groups on a voxel-wise basis. Voxel-wise results were clustered to statistically correct for multiple comparisons. The number of significant clusters within each group are reported as the outcome measure. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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 by arm
| Arm | Count |
|---|---|
| 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 | 29 |
| 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 | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Imaging Session (120 Min) | Lost to Follow-up | 0 | 2 |
| Imaging Session (120 Min) | Physician Decision | 0 | 1 |
| Imaging Session (120 Min) | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Misophonia Group | Emotional Dysregulation Clinical Group | Total |
|---|---|---|---|
| Age, Continuous | 29.59 years STANDARD_DEVIATION 9.79 | 27.07 years STANDARD_DEVIATION 8.28 | 28.31 years STANDARD_DEVIATION 9.06 |
| Difficulties in emotion regulation scale | 108.16 units on a scale STANDARD_DEVIATION 24.69 | 117.17 units on a scale STANDARD_DEVIATION 16.39 | 112.83 units on a scale STANDARD_DEVIATION 21.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 7 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 23 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| misophonia questionnaire severity | 9.18 units on a scale STANDARD_DEVIATION 1.63 | 3.45 units on a scale STANDARD_DEVIATION 2.47 | 6.26 units on a scale STANDARD_DEVIATION 3.56 |
| misophonia questionnaire Subscale 1 | 2.86 units on a scale STANDARD_DEVIATION 0.43 | 1.37 units on a scale STANDARD_DEVIATION 0.87 | 2.10 units on a scale STANDARD_DEVIATION 1.02 |
| misophonia questionnaire Subscale 2 | 2.83 units on a scale STANDARD_DEVIATION 0.38 | 1.08 units on a scale STANDARD_DEVIATION 0.69 | 1.97 units on a scale STANDARD_DEVIATION 1.04 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 10 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 17 Participants | 45 Participants |
| Region of Enrollment United States | 29 Participants | 30 Participants | 59 Participants |
| Sex: Female, Male Female | 26 Participants | 26 Participants | 52 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 8 / 27 | 4 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
Behavioral Outcome: Acceptability of Procedures
The investigators will record how many participants completed the neurostimulation session as a marker of acceptability.
Time frame: At the end of the neurostimulation session (session 3 in the experiment), which occured within a month of the initial assessment
Population: Participants who completed the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Misophonia Group | Behavioral Outcome: Acceptability of Procedures | 27 Participants |
| Emotional Dysregulation Clinical Group | Behavioral Outcome: Acceptability of Procedures | 27 Participants |
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.
Time frame: during the neuroimaging session, within a month of the intake assessment
Population: Participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Misophonia Group | 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 | .4572 BOLD arbitrary units | Standard Deviation 0.58605 |
| Emotional Dysregulation Clinical Group | 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 | .4288 BOLD arbitrary units | Standard Deviation 0.32026 |
Comparison: An independent samples t-test was conducted to examine differences between groups in BOLD bilateral dlPFC signal during the regulation of misophonic versus aversive sounds. One outlier was removed from the misophonia group to avoid violating the normality assumption.p-value: 0.5795% CI: [-0.14149, 0.25411]t-test, 2 sided
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.
Time frame: during the neuroimaging session, within a month of the intake assessment
Population: Participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Misophonia Group | Neuroimaging Outcome: Differential Change in BOLD Signal Within the Anterior Insular Cortex (AIC) Activation When Being Presented With Cues for Emotional Versus Misophonic Distress | .3744 BOLD arbitrary units | Standard Deviation 0.22996 |
| Emotional Dysregulation Clinical Group | Neuroimaging Outcome: Differential Change in BOLD Signal Within the Anterior Insular Cortex (AIC) Activation When Being Presented With Cues for Emotional Versus Misophonic Distress | .3093 BOLD arbitrary units | Standard Deviation 0.22876 |
Comparison: Mixed effects (FSL's FLAME 1; Oxford Univ., UK) whole brain analyses using cluster correction following a voxel-wise Z-score threshold of 2.3.p-value: <0.05mixed effects whole-brain using cluster
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.
Time frame: during the neuroimaging session, within a month of the intake assessment
Population: Participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Misophonia Group | Neuroimaging Outcome: Differential Change in BOLD Signal Within the Ventromedial Prefrontal Cortex (vmPFC) When Engaging in the Regulation of Emotional Versus Misophonic Distress | .4967 BOLD arbitrary units | Standard Deviation 0.61469 |
| Emotional Dysregulation Clinical Group | Neuroimaging Outcome: Differential Change in BOLD Signal Within the Ventromedial Prefrontal Cortex (vmPFC) When Engaging in the Regulation of Emotional Versus Misophonic Distress | .5233 BOLD arbitrary units | Standard Deviation 0.6043 |
Comparison: An independent samples t-test was conducted to examine differences between groups in vmPFC activation that was greater when downregulating misophonic versus non-misophonic distress. One participant from each group was excluded for being an outlierp-value: 0.77895% CI: [-0.22667, 0.301257]t-test, 2 sided
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.
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).
Population: Participants who completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to neutral sound+ sham stimulation | 1.8903 lg(ms^2) | Standard Deviation 0.49961 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a misophonic sound + LF rTMS | 1.8289 lg(ms^2) | Standard Deviation 0.48734 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to an aversive sound+ HF rTMS | 1.9753 lg(ms^2) | Standard Deviation 0.45907 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during aversive sounds + sham stimulation | 1.9216 lg(ms^2) | Standard Deviation 0.46655 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a neutral sound+ LF rTMS | 1.8923 lg(ms^2) | Standard Deviation 0.4136 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during aversive sounds + HF rTMS | 1.9319 lg(ms^2) | Standard Deviation 0.45462 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to an aversive sound + LF rTMS | 1.8942 lg(ms^2) | Standard Deviation 0.44218 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during aversive sounds + LF rTMS | 1.8740 lg(ms^2) | Standard Deviation 0.45462 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a neutral sound+ HF rTMS stimulation | 1.9420 lg(ms^2) | Standard Deviation 0.47814 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during misophonic sounds + sham stimulation | 1.9290 lg(ms^2) | Standard Deviation 0.4766 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a misophonic sound + sham stimulation | 1.8920 lg(ms^2) | Standard Deviation 0.44746 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during misophonic sounds + HF rTMS | 1.9259 lg(ms^2) | Standard Deviation 0.46639 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to an aversive sound+sham stimulation | 1.9172 lg(ms^2) | Standard Deviation 0.44301 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during misophonic sounds + LF rTMS | 1.8882 lg(ms^2) | Standard Deviation 0.4889 |
| Misophonia Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a misophonic sound + HF rTMS | 1.9680 lg(ms^2) | Standard Deviation 0.43347 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during misophonic sounds + LF rTMS | 1.9281 lg(ms^2) | Standard Deviation 0.58576 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a neutral sound+ HF rTMS stimulation | 1.9465 lg(ms^2) | Standard Deviation 0.52974 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a neutral sound+ LF rTMS | 1.9771 lg(ms^2) | Standard Deviation 0.61184 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to an aversive sound+sham stimulation | 1.9151 lg(ms^2) | Standard Deviation 0.49276 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to an aversive sound+ HF rTMS | 2.0791 lg(ms^2) | Standard Deviation 0.58066 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to an aversive sound + LF rTMS | 1.9590 lg(ms^2) | Standard Deviation 0.62018 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a misophonic sound + sham stimulation | 1.8868 lg(ms^2) | Standard Deviation 0.58837 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a misophonic sound + HF rTMS | 2.0457 lg(ms^2) | Standard Deviation 0.55137 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to a misophonic sound + LF rTMS | 1.9392 lg(ms^2) | Standard Deviation 0.61046 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during aversive sounds + sham stimulation | 1.9390 lg(ms^2) | Standard Deviation 0.61942 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during aversive sounds + HF rTMS | 2.0262 lg(ms^2) | Standard Deviation 0.55149 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during aversive sounds + LF rTMS | 1.9669 lg(ms^2) | Standard Deviation 0.64162 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during misophonic sounds + sham stimulation | 1.9362 lg(ms^2) | Standard Deviation 0.56408 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | downregulate emotions during misophonic sounds + HF rTMS | 1.9962 lg(ms^2) | Standard Deviation 0.57097 |
| Emotional Dysregulation Clinical Group | Physiological Outcome: High Frequency Heart Rate Variability (HF-HRV) Recorded During Experimental Blocks | listen to neutral sound+ sham stimulation | 1.9422 lg(ms^2) | Standard Deviation 0.51434 |
Comparison: A MMANOVA analysis using an unstructured covariance structure examined main effects of experimental group, instruction provided, headache, racial background, and type of neurostimulation administered. HF-HRV was transformed using an lg function for normality.p-value: 0.22195% CI: [-0.12, 0.029]Mixed Models Analysis
Comparison: A MMANOVA analysis using an unstructured covariance examined the main effect of type of neurostimulation providedp-value: 0.00895% CI: [0.016, 0.103]Mixed Models Analysis
Comparison: A MMANOVA analysis using an unstructured covariance structure examined the main effect of type of neurostimulation provided.p-value: 0.00195% CI: [0.029, 0.111]Mixed Models Analysis
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.
Time frame: Two minute blocks during the neurostimulation experimental session (when participants listened to or downregulated emotions associated with experimental sounds)
Population: Participants who completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Misophonia Group | Skin Conductance Level (SCL) | listen to neutral sounds + sham stimulation | 8.42392 microsemens | Standard Deviation 3.228892 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to neutral sounds + HF rTMS | 8.51538 microsemens | Standard Deviation 3.82094 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to neutral sounds + LF rTMS | 8.39378 microsemens | Standard Deviation 3.569227 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to aversive sounds + sham stimulation | 9.18323 microsemens | Standard Deviation 3.275174 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to aversive sounds + HF rTMS | 9.56538 microsemens | Standard Deviation 4.100446 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to aversive sounds + LF rTMS | 9.41889 microsemens | Standard Deviation 3.675953 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to misophonic sounds + sham stimulation | 8.83446 microsemens | Standard Deviation 3.160085 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to misophonic sounds + HF rTMS | 8.68612 microsemens | Standard Deviation 3.446615 |
| Misophonia Group | Skin Conductance Level (SCL) | listen to misophonic sounds + LF rTMS | 8.89759 microsemens | Standard Deviation 3.950378 |
| Misophonia Group | Skin Conductance Level (SCL) | downregulate distress associated with aversive sounds+ sham stimulation | 8.5036 microsemens | Standard Deviation 3.5264 |
| Misophonia Group | Skin Conductance Level (SCL) | downregulate distress associated with aversive sounds+ HF rTMS | 8.51065 microsemens | Standard Deviation 3.714333 |
| Misophonia Group | Skin Conductance Level (SCL) | downregulate distress associated with aversive sounds+ LF rTMS | 8.34333 microsemens | Standard Deviation 3.567143 |
| Misophonia Group | Skin Conductance Level (SCL) | downregulate distress associated with misophonic sounds+ sham stimulation | 8.66058 microsemens | Standard Deviation 3.438065 |
| Misophonia Group | Skin Conductance Level (SCL) | downregulate distress associated with misophonic sounds+ HF rTMS | 8.38327 microsemens | Standard Deviation 3.611908 |
| Misophonia Group | Skin Conductance Level (SCL) | downregulate distress associated with misophonic sounds+ LF rtMS | 8.43874 microsemens | Standard Deviation 3.658122 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | downregulate distress associated with misophonic sounds+ LF rtMS | 8.82144 microsemens | Standard Deviation 5.888309 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to misophonic sounds + HF rTMS | 9.68599 microsemens | Standard Deviation 5.220985 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to neutral sounds + sham stimulation | 8.90082 microsemens | Standard Deviation 5.259539 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | downregulate distress associated with aversive sounds+ LF rTMS | 8.82512 microsemens | Standard Deviation 5.85035 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to neutral sounds + HF rTMS | 9.30579 microsemens | Standard Deviation 5.232129 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to misophonic sounds + LF rTMS | 8.85123 microsemens | Standard Deviation 5.617469 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to neutral sounds + LF rTMS | 8.83644 microsemens | Standard Deviation 5.731341 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | downregulate distress associated with misophonic sounds+ HF rTMS | 9.37240 microsemens | Standard Deviation 5.049701 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to aversive sounds + sham stimulation | 9.40404 microsemens | Standard Deviation 5.249783 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | downregulate distress associated with aversive sounds+ sham stimulation | 8.88481 microsemens | Standard Deviation 5.501042 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to aversive sounds + HF rTMS | 10.45648 microsemens | Standard Deviation 5.39588 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | downregulate distress associated with misophonic sounds+ sham stimulation | 8.64721 microsemens | Standard Deviation 5.321361 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to aversive sounds + LF rTMS | 9.51379 microsemens | Standard Deviation 5.67776 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | downregulate distress associated with aversive sounds+ HF rTMS | 9.53835 microsemens | Standard Deviation 5.269438 |
| Emotional Dysregulation Clinical Group | Skin Conductance Level (SCL) | listen to misophonic sounds + sham stimulation | 9.17171 microsemens | Standard Deviation 5.249371 |
Comparison: 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 headachep-value: 0.3495% CI: [-0.243, 0.689]Mixed Models Analysis
Comparison: 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 headachep-value: 0.00195% CI: [0.198, 0.787]Mixed Models Analysis
Comparison: 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 headachep-value: 0.00295% CI: [0.182, 0.757]Mixed Models Analysis
Comparison: 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).p-value: 0.0005Mixed Models Analysis
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.
Time frame: Baseline, during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment)
Population: Participants who completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to aversive sounds + HF rTMS | 0.6019 units on a scale | Standard Deviation 2.11131 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to misophonic sounds + LF rTMS | 3.7037 units on a scale | Standard Deviation 2.6449 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to neutral sounds + HF rTMS | -0.5769 units on a scale | Standard Deviation 1.45277 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with aversive sounds+ sham stimulation | 0.7184 units on a scale | Standard Deviation 1.59913 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to aversive sounds + LF rTMS | 0.8981 units on a scale | Standard Deviation 1.66851 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with aversive sounds+ HF rTMS | -0.0288 units on a scale | Standard Deviation 1.56079 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to aversive sounds + sham stimulation | 1.3107 units on a scale | Standard Deviation 1.94548 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with aversive sounds+ LF rTMS | 0.2685 units on a scale | Standard Deviation 1.27965 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to misophonic sounds + sham stimulation | 4.4712 units on a scale | Standard Deviation 2.38505 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with misophonic sounds+ sham stimulation | 3.3173 units on a scale | Standard Deviation 2.45845 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to neutral sounds + LF rTMS | -0.2130 units on a scale | Standard Deviation 1.61795 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with misophonic sounds+ HF rTMS | 2.0673 units on a scale | Standard Deviation 2.70298 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to misophonic sounds+ HF rTMS | 3.3269 units on a scale | Standard Deviation 2.71079 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with misophonic sounds+ LF rTMS | 2.50000 units on a scale | Standard Deviation 2.71548 |
| Misophonia Group | Change in Subjective Units of Distress (SUDS) | listen to neutral sounds + sham stimulation | 0.2981 units on a scale | Standard Deviation 1.35732 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with misophonic sounds+ LF rTMS | 0.7778 units on a scale | Standard Deviation 1.38977 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to neutral sounds + sham stimulation | 0.5370 units on a scale | Standard Deviation 1.25621 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to neutral sounds + HF rTMS | -0.3611 units on a scale | Standard Deviation 1.97866 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to neutral sounds + LF rTMS | 0.3056 units on a scale | Standard Deviation 1.33576 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to aversive sounds + sham stimulation | 2.8795 units on a scale | Standard Deviation 2.18199 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to aversive sounds + HF rTMS | 1.8505 units on a scale | Standard Deviation 2.21404 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to aversive sounds + LF rTMS | 2.5463 units on a scale | Standard Deviation 2.25224 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to misophonic sounds + sham stimulation | 2.3426 units on a scale | Standard Deviation 2.02398 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to misophonic sounds+ HF rTMS | 0.9815 units on a scale | Standard Deviation 2.28764 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | listen to misophonic sounds + LF rTMS | 1.9252 units on a scale | Standard Deviation 1.98438 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with aversive sounds+ sham stimulation | 1.3148 units on a scale | Standard Deviation 1.29448 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with aversive sounds+ HF rTMS | 0.1574 units on a scale | Standard Deviation 1.74636 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with aversive sounds+ LF rTMS | 1.0926 units on a scale | Standard Deviation 1.38441 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with misophonic sounds+ sham stimulation | 1.0472 units on a scale | Standard Deviation 1.35494 |
| Emotional Dysregulation Clinical Group | Change in Subjective Units of Distress (SUDS) | downregulate distress associated with misophonic sounds+ HF rTMS | -0.2963 units on a scale | Standard Deviation 1.49303 |
Comparison: The MMANOVA analysis of SUDS used a Toeplitz covariance structure. 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.p-value: 0.4995% CI: [-0.766, 0.372]Mixed Models Analysis
Comparison: 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.p-value: <1e-795% CI: [0.62, 1.97]Mixed Models Analysis
Comparison: 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.p-value: 0.01895% CI: [0.057, 0.605]Mixed Models Analysis
Comparison: 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.p-value: <0.000001Mixed Models Analysis
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.
Time frame: From baseline to the end of neurostimulation session, an average of 4 weeks.
Population: Some participants dropped out or were lost to contact by follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Misophonia Group | Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS) | Baseline | 93.04 score on a scale | Standard Deviation 21.17 |
| Misophonia Group | Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS) | End of neurostimulation session | 88.70 score on a scale | Standard Deviation 21.76 |
| Emotional Dysregulation Clinical Group | Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS) | Baseline | 112.43 score on a scale | Standard Deviation 16.42 |
| Emotional Dysregulation Clinical Group | Emotional Dysregulation as Measured by the Difficulties in Emotion Regulation Scale (DERS) | End of neurostimulation session | 99.85 score on a scale | Standard Deviation 17.75 |
Comparison: Repeated measures ANOVA (controlling for racial background)p-value: <0.001ANCOVA
Comparison: Repeated measures ANOVA (controlling for racial background)p-value: >0.012ANCOVA
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.
Time frame: during the neuroimaging session, within a month of the intake assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Misophonia Group | 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 | 0 clusters |
| Emotional Dysregulation Clinical Group | 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 | 0 clusters |
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).
Time frame: during the neuroimaging session, within a month of the intake assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Misophonia Group | 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 | 1 clusters |
| Emotional Dysregulation Clinical Group | 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 | 0 clusters |
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.
Time frame: During the neuroimaging session, within a month of the intake assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Misophonia Group | Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Aversive Versus Neutral Sounds. | 0 clusters where differences emerged |
| Emotional Dysregulation Clinical Group | Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Aversive Versus Neutral Sounds. | 0 clusters where differences emerged |
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.
Time frame: during the neuroimaging session, within a month of the intake assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Misophonia Group | Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Misophonic Versus Aversive Sounds. | 6 clusters |
| Emotional Dysregulation Clinical Group | Number of Clusters Across the Whole Brain With Significant BOLD Changes Between Groups When Contrasting the Exposure to Misophonic Versus Aversive Sounds. | 3 clusters |
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.
Time frame: At baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Misophonia Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43-Fatigue | 14.97 score on a scale | Standard Deviation 7.27 |
| Misophonia Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43- Ability to partake in social roles | 23.86 score on a scale | Standard Deviation 4.6 |
| Misophonia Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43 Depression | 11.28 score on a scale | Standard Deviation 6.05 |
| Misophonia Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43-Pain interference | 7.59 score on a scale | Standard Deviation 3.09 |
| Misophonia Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43- Sleep disturbance | 13.24 score on a scale | Standard Deviation 6.26 |
| Misophonia Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43-Physical functioning | 29.76 score on a scale | Standard Deviation 3.11 |
| Misophonia Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43 Anxiety | 14.10 score on a scale | Standard Deviation 5.37 |
| Emotional Dysregulation Clinical Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43-Physical functioning | 28.73 score on a scale | Standard Deviation 2.36 |
| Emotional Dysregulation Clinical Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43 Anxiety | 13.70 score on a scale | Standard Deviation 5.73 |
| Emotional Dysregulation Clinical Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43 Depression | 13.03 score on a scale | Standard Deviation 6.49 |
| Emotional Dysregulation Clinical Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43-Fatigue | 15.80 score on a scale | Standard Deviation 6.27 |
| Emotional Dysregulation Clinical Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43- Sleep disturbance | 15.30 score on a scale | Standard Deviation 4.83 |
| Emotional Dysregulation Clinical Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43- Ability to partake in social roles | 23.07 score on a scale | Standard Deviation 5.66 |
| Emotional Dysregulation Clinical Group | Self-reported Health Status as Measured by the Patient Reported Outcome Measurement Information System (PROMIS)-43 Adult Profile | P43-Pain interference | 7.93 score on a scale | Standard Deviation 3.11 |
Comparison: An independent samples t-test was conducted to examine between group differences at the intake assessment on the PROMIS Anxiety subscalep-value: 0.78t-test, 2 sided
Comparison: An independent samples t-test was conducted to examine between group differences at the intake assessment on the PROMIS Depression subscalep-value: 0.29t-test, 2 sided
Comparison: An independent samples t-test was conducted to examine between group differences at the intake assessment on the PROMIS Fatigue subscalep-value: 0.64t-test, 2 sided
Comparison: An independent samples t-test was conducted to examine between group differences at the intake assessment on the PROMIS Sleep disturbance subscalep-value: 0.16t-test, 2 sided
Comparison: 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 subscalep-value: 0.56t-test, 2 sided