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This is a study to find out if a cutting-edge technology called transcranial focused ultrasound (tFUS) can be used to treat how people with anxiety or related concerns cope with emotional situations. tFUS is a brain stimulation technology that causes temporary changes in the activity of deep brain areas without a need for any surgery or other permanent or invasive procedures.
This study is recruiting participants who recently started treatment for anxiety or a related concern to come in for 3 visits at the Medical University of South Carolina. At the first visit, participants will do interviews and surveys asking about anxiety and related concerns, and they do tasks where they respond to emotional pictures while brain activity is measured using magnetic resonance imaging (MRI). At the next two visits, participants again do a task where they see and react to emotional images, and this time the task is done once before and again once after receiving tFUS that either actively causes temporary changes (lasting for about an hour) in a targeted brain area or is not active (no changes elicited). At each tFUS visit, responses are measured with sensors worn on the hand, arms, face, and head (these visits do not involve MRI).
Each visit in this study is expected to last between 2 - 3 hours. This study is not a treatment study, but it could help improve treatment in the future. Participants in this study are paid for their time.
Escape and avoidance are core targets of anxiety and related disorder treatment, but such behaviors also often persist even after reduction of reported symptoms or they keep an individual from engaging in treatment at all. Novel methods to directly target motive drivers of escape/ avoidance coping early in treatment are needed to improve retention and outcome especially for the 20% of individuals who do not benefit from and 40% who do not complete treatment. Basic science identifies multiple neural mediators of real-world escape and avoidance, and it suggests these mediators may not be directly or adequately targeted by current treatment techniques. Moreover, the direct neural mediators may be primarily subcortical and thus not be accessible to therapeutic technologies like transcranial magnetic stimulation that can only stimulate cortical areas. A novel technology called transcranial focused ultrasound (tFUS), meanwhile, has demonstrated ability to non-invasively and stimulate even the deepest areas of the brain in humans, and thus may have utility in directly modulating the subcortical drivers of exaggerated escape/ avoidance coping. Given this exciting possibility, the primary goal of this research is to determine if tFUS to subcortical neural mediators can be used to cause measurable changes in the downstream escape/ avoidance dispositions. Results will then inform the potential use of noninvasive tFUS stimulation as a precursor to evidence-based therapy to reduce risk of dropout and enhance outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group Receiving Active Stimulation and Sham Stimulation on Separate Days (All Participants) | Experimental | All participants will receive active stimulation and non-active (sham) stimulation on different days. Before the stimulation sessions, all participants will complete experimental tasks during functional magnetic resonance imaging. On the next two study days, all participants will complete tasks before and after receiving active transcranial focused ultrasound (tFUS) on one day and sham (non-active) tFUS on another day. Stimulation (active or sham) is conducted briefly (< 10 minutes) in between tasks, not during tasks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active transcranial focused ultrasound (tFUS) | Device | Active non-invasive low-intensity focused ultrasound will be delivered using a proprietary head-worn device and control software from Attune Neurosciences. On an active stimulation day, focused ultrasound will be delivered to the brain region of interest using parameters from published research that are demonstrated to safely cause temporary changes in the activity in that brain area. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fear-Potentiated Startle Reflex | Fear-potentiated startle is measured during an experimental task in which participants prepare to avoid, escape, or simply be exposed to aversive pictures. Fear-potentiated startle measures motivational activation during the preparation period. | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in speed to initiate avoidance behavior | Reaction time to initiate flight is measured in an experimental task in which participants change the size of pleasant or unpleasant images with a joystick. Reaction time measures behavioral tendency toward avoidance in the presence of unpleasant images or approach in the presence of pleasant images | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Measure | Description | Time Frame |
|---|---|---|
| Task-Related Regional Brain Activation | Blood flow in the brain will be measured during completion of an experimental escape/ avoidance task using functional magnetic resonance imaging (fMRI). Blood flow in the brain can be used to measure what brain areas are being activated during the performance of a task. | During Session (Approx. 45 minutes) |
Inclusion Criteria:
Exclusion Criteria:
Note: selective serotonin re-uptake inhibitors (SSRIs), cholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists are allowed if patient has been on a stable regimen of four weeks prior to enrollment
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Christopher T Sege, PhD | Contact | (843) 501-1718 | sege@musc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Christopher Sege, PhD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina | Recruiting | Charleston | South Carolina | 29425 | United States |
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| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
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| Sham transcranial focused ultrasound (tFUS) | Device | Non-active low-intensity ultrasound will also be conducted using a proprietary head-worn device and control software from Attune Neurosciences. On the sham stimulation day, the device will be activated in a manner that produces similar sensory effects (i.e., low-volume beeping-type noise from the device) but also prevents delivery of a focused ultrasound beam to the brain area of interest or any other brain area. |
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| Change in Electroencephalography (EEG)-Assessed Contingent Negative Variation During Escape/ Avoidance Preparation | Brain electroencephalography (EEG) is measured non-invasively with sensors placed on top of the head during all pre/ post-stimulation experimental tasks. The Contingent Negative Variation (CNV) is an event-related potential measure of motor preparation processing that arises in S1-S2-type tasks. | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Change in Electroencephalography (EEG)-Assessed N200 During Implicit Approach/ Avoid Bias Assessment | Brain electroencephalography (EEG) is measured non-invasively with sensors placed on top of the head during all pre/ post-stimulation experimental tasks. The N200 is an event-related potential measure of neural stimulus-response conflict that can be used to index the degree to which unpleasant stimuli facilitate avoidant behavior. | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Change in Electroencephalography (EEG)-Assessed Theta-Band Power During Behavioral Tasks | Brain electroencephalography (EEG) is measured non-invasively with sensors placed on top of the head during all pre/ post-stimulation experimental tasks. Power in a theta frequency band is a measure of cognitive control that will be assayed in all behavioral tasks as a measure of task engagement changes | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Change in High-Frequency Heart Rate Variability/ Respiratory Sinus Arrhythmia | Heart rate and also respiration are measured during all pre/ post-stimulation experimental tasks. These measures can be combined to derive an index of the strength of vagal control over the heart (High-Frequency Heart Rate Variability/ Respiratory Sinus Arrhythmia) that reflects greater attentional control relative to stress (i.e., sympathetic) responding. This measure will be assayed in all tasks and in resting measurements conducted pre- and post-stimulation. | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Change in Task-Based Heart Rate (Beats per Minute) Changes | Heart rate is measured during all pre/ post-stimulation experimental tasks. Task event-related changes in heart rate will be measured as an index of the strength of attentional orienting to all motivationally relevant cues | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Change in Task-Based Galvanic Skin Conductance | Skin conductance is measured during all pre/ post-stimulation experimental tasks from sensors placed on the hand. Skin conductance can be indexed to test for changes in sympathetic activation during escape/ avoidance preparation. | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |
| Change in State Anxiety During Session | State-level anxiety is measured throughout the experimental session using the State-Trait Anxiety Inventory - State Form. The State-Trait Anxiety Inventory - State Form uses 20 items querying anxiety symptom experience in the present moment to measure how anxiety fluctuates across the experimental session. The scale ranges from 20 to 80, with higher scores indicating higher state anxiety. | Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments) |