Identifying the Optimal Neural Target for Misophonia Interventions

NCT04348591 | Completed Results FDA Device

• 1 other identifier: Pro00103863
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Misophonia; Emotion Dysregulation

Keywords

neurostimulation; neuroscience; misophonia; emotion dysregulation; insula

Outcome Measures

Primary Outcomes (6)

• 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.

  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

Secondary Outcomes (7)

• 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)

• 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.

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

  At baseline

• 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

• 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

Study Arms (2)

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.

Behavioral: Cognitive Restructuring; Device: neurostimulation

Emotional Dysregulation Clinical Group

ACTIVE COMPARATOR

Participants who self report high emotional dysregulation and who meet diagnostic criteria for a DSM disorder will undergo a neuroimaging session to identify different neurostimulation targets. Then these participants will be exposed to aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets.

Behavioral: Cognitive Restructuring; Device: neurostimulation

Interventions

Cognitive Restructuring BEHAVIORAL

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

Emotional Dysregulation Clinical Group; Misophonia Group

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

Also known as: transcranial magnetic stimulation

Emotional Dysregulation Clinical Group; Misophonia Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• stable psychotherapy and medication for at least 4 weeks
• self reports high emotional dysregulation OR misophonia
• Participants will be matched on gender and age between the two groups

Sponsors & Collaborators

• Duke University: lead
• Misophonia Research Fund: collaborator

Study Sites (1)

Duke University Medical Center-Civitan Bldg

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

misophonia

Interventions

Cognitive Restructuring; Transcranial Magnetic Stimulation

Intervention Hierarchy (Ancestors)

Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Magnetic Field Therapy; Therapeutics

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Andrada D. Neacsiu
• Organization: Duke University

andrada.neacsiu@duke.edu

919-684-6714

Study Officials

• Andrada D Neacsiu, PhD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 16, 2020
• Study Start: October 28, 2020
• Primary Completion: May 27, 2022
• Study Completion: May 28, 2022
• Last Updated: August 25, 2023
• Results First Posted: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: 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.
• Access Criteria: Open to any researcher to view and access.

Locations

US (1)