Using Neurostimulation to Accelerate Change in Misophonia: a Pilot Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Duke University
- Enrollment
- 59
- Locations
- 2
- Primary Endpoint
- Number of clusters across the whole brain with significant BOLD changes between conditions contrasting follow up with intake, and downregulation of versus exposure to misophonic sounds
Study Overview
Brief Summary
Misophonia, the inability to tolerate certain repetitive distressing sounds that are common, is gaining, recognition as an impairing condition. It is not a well-understood condition and there are no known treatments. The purpose of this study is to test a new misophonia intervention that uses emotion regulation strategies and different types of brain stimulation on misophonic distress. This study will examine changes in brain activity during presentation and regulation of misophonic versus distressing sounds. The study team plans to alter activity in a key area of the brain responsible for emotion regulation circuitry over 4 sessions with the goal to test if this intervention helps misophonic distress.
Sixty adult participants with moderate to severe misophonia will be recruited and taught an emotion regulation skill and randomly assigned to receive one of two types of repetitive transcranial magnetic stimulation (rTMS). The study includes 9-10 visits: the remote screening visit(s), the initial MRI, the four neurostimulation sessions, the follow-up MRI, and two additional remote 1- and 3-month follow-up visits.
Detailed Description
Given the urgent need for interventions for misophonia, the primary purpose of this study is to establish short and long-term effects for an intervention that combines emotion regulation with neurostimulation. The secondary goal is to examine the best parameters needed for a successful intervention. It is important to highlight that the study findings would not only inform future behavioral and neurostimulation interventions but may also provide critical information for other intervention approaches that aim to alter neural circuitry involved in misophonia.
Interested participants who pass the online and phone screen are scheduled for the first study visit that will be conducted remotely. Those who are interested and provide e-consent, will complete demographic questions and several interviews and measures aimed to examine misophonic and psychiatric distress, verbal IQ, treatment history, and MRI/neurostimulation safety. Participants will listen to a set of standardized aversive and misophonic sounds and rate how distressing they find them. They will also be invited to send recordings of their own misophonic sounds in different contexts and together with them and other standardized misophonic sounds, they will listen to the sounds and rate their distress. The goal in the study is to generate a personalized set of triggers that includes personalized misophonic, aversive and neutral sounds for each participant.
The type of neuromodulation that is being tested in the study is repetitive transcranial magnetic stimulation (rTMS), a procedure which involves placement of an electromagnetic coil over the scalp that produces very small electric currents in the part of the brain that is closest to the coil. rTMS is a noninvasive procedure that is currently approved by the Food and Drug Administration (FDA) for the treatment for depression, obsessive compulsive disorder, and smoking. In this study, rTMS will be used differently than what has been approved for by the FDA but within safety guidelines.
The goal of the study is to enroll sixty eligible adult participants with misophonia who will then be asked to come to Duke for the initial brain MRI visit. Following established procedures, participants will be briefly taught CR (cognitive restructuring), an emotion regulation strategy selected because it successfully adjusts the emotion regulation network. Participants will undergo a functional neuroimaging (MRI) task based on which a personalized neurostimulation target will be established.
Participants will then be randomly assigned to active or sham rTMS intervention matching on age, gender at birth and misophonia impairment severity. Participants will then undergo four consecutive intervention sessions during which they will receive either type of rTMS over their personalized target on the right side of the brain while being exposed to personalized misophonic cues and instructed to engage in cognitive emotion regulation. At the initial TMS visit, all participants will be trained in CR in depth using a standardized training session. During each neurostimulation session, biophysiological data including heart rate and skin conductance will be collected.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description
All participants will engage in a behavioral training session (Cognitive Restructuring).
The study team member who will conduct the behavioral session will be kept blind to the type of neurostimulation the participant will receive. Participants will also be kept blinded to what neurostimulation they receive and their perception of what they received will be assessed at follow-up. The intervention provider will also be kept blind to the treatment condition to ensure non-biased administration of the intervention.
Participants will only be told about the type of neurostimulation at the end of the study to protect against different expectations
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •verbal agreement to maintain dose of prescribed psychotropic medication (if any) and/or psychotherapy (if any) constant throughout the study, provided they are stable on it for the past 4 weeks (except exclusion medication and except if there is a medical emergency requiring changes in medication).
- •DMQ Impairment score >= 14
Exclusion Criteria
- •current or past history of mania or psychosis; current hypomania
- •verbal IQ< 90 as per the NART
- •not medically cleared for TMS or fMRI (such as taking medications known to reduce the seizure threshold such as Lithium, Clozaril, stimulants including the ADHD medications (e.g. Ritalin, Adderall), Wellbutrin/Buproprion, Provigil (Modafinil), Aminophylline, and Theophylline)
- •DMQ Impairment score < 14
- •younger than 18 and older than 55
- •high risk for suicide (defined as having attempted suicide in past 6 months; suicide attempt within the past 10 years with current ideation with plan or preferred method available)
- •moderate/severe current alcohol or substance use disorder, or past severe alcohol use disorder
- •unable to read, blind, or deaf, or unwilling to give consent
- •cannot come to Duke for the in-person study visits
- •current uncontrolled anorexia or other condition requiring hospitalization
- •conditions associated with increased intracranial pressure, space occupying brain lesion, transient ischemic attack, cerebral aneurysm, dementia, Parkinson's or Huntington's disease, multiple sclerosis
- •use of investigational drug or devices within 4 weeks of screening
- •started/changed psychotropic medications or started psychotherapy in the prior 4 weeks, or plans to change medication or stop psychotherapy during the study
Arms & Interventions
Cognitive Restructuring + High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS)
30 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while being exposed to misophonic trigger sounds and also receiving high frequency rTMS over their personalized right dorsal lateral prefrontal cortex (dlPFC) target. These participants will partake in short term and long term follow-up testing.
Intervention: High Frequency Repetitive Transcranial Magnetic Stimulation (HF rTMS) (Device)
Cognitive Restructuring + Shame Repetitive Transcranial Magnetic Stimulation (rTMS)
30 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while being exposed to misophonic trigger sounds and also receiving placebo rTMS over their personalized right dorsal lateral prefrontal cortex (dlPFC) target. These participants will partake in short term and long term follow-up testing.
Intervention: Sham Repetitive Transcranial Magnetic Stimulation (sham- rTMS) (Device)
Cognitive Restructuring + Shame Repetitive Transcranial Magnetic Stimulation (rTMS)
30 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while being exposed to misophonic trigger sounds and also receiving placebo rTMS over their personalized right dorsal lateral prefrontal cortex (dlPFC) target. These participants will partake in short term and long term follow-up testing.
Intervention: Cognitive Restructuring (Behavioral)
Cognitive Restructuring + High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS)
30 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while being exposed to misophonic trigger sounds and also receiving high frequency rTMS over their personalized right dorsal lateral prefrontal cortex (dlPFC) target. These participants will partake in short term and long term follow-up testing.
Intervention: Cognitive Restructuring (Behavioral)
Outcomes
Primary Outcomes
Number of clusters across the whole brain with significant BOLD changes between conditions contrasting follow up with intake, and downregulation of versus exposure to misophonic sounds
Time Frame: during the neuroimaging session, within 2 months 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. For each participant, the difference in BOLD activation between follow up and intake was computed. The BOLD signal contrast between downregulating and engaging with misophonic sounds were compared between conditions 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 condition are presented as outcome.
Change in Subjective Unites of Distress (SUDS)
Time Frame: Baseline, during the experimental blocks of the neurostimulation sessions (which will occur over 4 days within a month of the initial assessment)
Self reported distress after each sound presentation will also be examined for differences when accounting for baseline distress (during the neurostimulation sessions). 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 misophonic sound presentations minus SUDS after baseline. Higher SUDS represents higher distress.
Number of clusters across the whole brain with significant BOLD changes between conditions contrasting follow up with intake, and exposure to misophonic versus aversive sounds
Time Frame: during the neuroimaging session, within 2 months 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. For each participant,the difference in BOLD activation between follow up and intake was computed. The BOLD signal contrast between engaging with misophonic sounds and engaging with aversive sounds were compared between conditions 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 condition are presented as outcome.
Differential change in BOLD signal connectivity between the left Anterior Insular Cortex (AIC) and the right dorsolateral prefrontal cortex (dlPFC) when downregulating versus experiencing distress related to misophonic trigger sounds
Time Frame: during the neuroimaging session, within 2 months 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). For each participant, change in activation during the \[downregulate vs. listen to misophonic sounds\] contrast from baseline to follow up will be computed. A left anterior insular cortex (AIC) mask will be employed to find the maximum value for the contrast of interest in this region. A psychophysiological interaction (PPI) analysis will be conducted, to identify the voxel within the right dlPFC with the highest positive correlation with the max activation AIC voxel. A sphere ROI will be created around this right dlPFC spot (restricted with a dlPFC mask) and the average contrast value within this sphere will be used as the outcome connectivity variable. A larger score indicates more connectivity when downregulating versus hearing misophonic sounds.
Differential change in BOLD signal within the Anterior Insular Cortex (AIC) activation when being presented with misophonic versus non-misophonic but aversive sounds
Time Frame: during the neuroimaging session, within 2 months 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. For each participant, change in activation during the presentation of misophonic versus aversive sounds from baseline to follow up will be computed. An anterior insular cortex (AIC) mask will be employed to find the maximum value of the \[hear misophonic sounds \> hear aversive sounds\] contrast in this region. Once the voxel containing this maximum will beidentified, a sphere ROI will be 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.
Change in misophonia impairment and severity using a composite
Time Frame: Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up
Change in misophonia impairment and severity will be investigated by using a composite score that will be created from the following scales and interview to examine changes in misophonia impairment and severity: the Duke Misophonia Questionnaire (DMQ), the Duke Misophonia Interview (DMI), the Duke-Vanderbilt Misophonia Screening Questionnaire (DVMSQ). A higher score on the DMQ impairment indicates more impairment (ranges 0-48). Similarly, higher scores on the DVMSQ and DMI indicate higher levels of impairment and distress. These measures are collected at all possible time points, depending on the range of time that they cover (e.g., DMI is not collected at 1 week follow up because it asks for impairment in the past month).
Skin conductance level (scl)
Time Frame: Baseline, and two minute blocks during the 4 neurostimulation sessions (when participants downregulate emotions associated with misophonic triggers)
Physiological arousal measured by SCL during each neurostimulation visit will be extracted using Acqknowledge software and BIOPAC hardware. Raw galvanic skin response will be continuously collected throughout the experiment. Raw data will then be examined for abrupt changes (skin conductance responses), which will be removed. The processed data will then be averaged for each experimental block. Higher SCL means higher arousal.
Secondary Outcomes
- Changes in clinician-assessed psychopathology(Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up)
- Emotional dysregulation as measured by the Difficulties in Emotion Regulation Scale (DERS)(Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up)
- Changes in self-reported psychopathology(Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up)