LIFU for Anxiety Management

Study Overview
=================
Brief Summary
-----------------
This study is examining the effects of noninvasive brain stimulation on anxiety. Low-intensity focused ultrasound (LIFU) will be utilized to neuromodulate the brain prior to a task (NPU). Physiological recordings will be taken throughout (EEG, EMG, HR, BP, RR, GSR).

Detailed Description
-----------------
This study is a research project examining the effects of noninvasive brain stimulation on anxiety. This study will help us to better understand possible treatments for patients diagnosed with anxiety disorders. Participants will undergo a functional magnetic resonance imaging (fMRI) and a computed tomography (CT) scan, to image the bone and brain tissue. Participants will receive noninvasive brain stimulation using low-intensity focused ultrasound (LIFU) sound waves, to temporarily change brain activity. Participants will undergo a threat task involving brief (100ms) shocks (1-5mA) and startle noises. Brain signals (EEG), muscle twitch (EMG), heart rate and rhythm, blood pressure, respiration rate, and skin moisture will be monitored throughout. Participants will be asked to complete behavioral questionnaires.

Official Title
-----------------
Investigation of Low-intensity Focused Ultrasound for Human Anxiety Management

Conditions
-----------------
Anxiety

Intervention / Treatment
-----------------
* Device: Low-intensity focused ultrasound
* Device: Low-intensity focused ultrasound - sham


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: High or low trait anxiety Exclusion Criteria: claustrophobia Contraindications to MRI (implants) Contraindications to CT (pregnancy) Active medical disorder with CNS effects (e.g. Alzheimers) History of neurologic disorder (e.g. Parkinson's, epilepsy) History of head injury w/ LOC for >10 min History of alcohol or drug dependence History of current cardiovascular disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will act as their own sham - sham vs real will be conducted in separate study visits. 2 arms exist for 2 variations of the NPU task.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPU<br>Participant will be presented with a series of images (cues) and sounds. Three conditions will occur - a no shock (N), predictable shock (P), and unpredictable shock (U). In P, shocks will only occur with the cue. In U, shocks will happen at any time. Participants will be told which condition they are in throughout the task. Startle sounds will occur throughout. 3 Study visits will occur - identical conditions for the participant, testing 2 brain regions and 1 sham visit. | Device: Low-intensity focused ultrasound<br>* A noninvasive brain stimulation device using low-intensity focused ultrasound (LIFU) - ultrasound will be used to test whether noninvasive brain stimulation can reduce reactions to sensory stimuli.<br>Device: Low-intensity focused ultrasound - sham<br>* A sham condition that will mimic the application of LIFU without actually administering any ultrasound to the brain.<br>|
| Experimental: NPU-c<br>Participants will be presented with a moving line. When the line reaches a certain point - an event will occur. This event will either be a painful shock or a monetary reward. Startle sounds will occur throughout. 3 study visits will occur - identical conditions for the participant, testing 2 brain regions and 1 sham visit. | Device: Low-intensity focused ultrasound<br>* A noninvasive brain stimulation device using low-intensity focused ultrasound (LIFU) - ultrasound will be used to test whether noninvasive brain stimulation can reduce reactions to sensory stimuli.<br>Device: Low-intensity focused ultrasound - sham<br>* A sham condition that will mimic the application of LIFU without actually administering any ultrasound to the brain.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in EMG eye startle reflex | Attenuated amplitude of startle reflex during uncertain and predictable threat tasks with lifu compared to sham. | Through study completion, an average of 2 weeks | 
| Change in heart rate using ECG | Attenuation of hear rate increases due to startle tasks in lifu compared to sham condition | Through study completion, an average of 2 weeks |