Low-intensity Focused Ultrasound and Autonomic Response

Study Overview
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Brief Summary
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Studying the effects of Low Intensity Focused Ultrasound (LIFU) to the dorsal anterior insula (dAI) and dorsal anterior cingulate cortex (dACC) on autonomic control using three tests to probe the autonomic system. A cold pressor task, valsalva maneuver, and deep breathing tasks will be performed pre and post LIFU application. Physiologic recordings will be recorded throughout.

Detailed Description
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Characterize the effect of LIFU to the bilateral dorsal anterior insula (dAI) and dorsal anterior cingulate cortex (dACC)) on autonomic control. The dAI is a critical brain area involved in autonomic function with evidence suggesting the right vs left dAI contribute differently to autonomic control, preferentially processing sympathetic and parasympathetic processing, respectively. Similarly, the dACC has been strongly implicated in autonomic control and works with the insula for autonomic processing. Inconveniently, these brain regions lie deep to the cortex, prohibiting access using conventional noninvasive methods like transcranial magnetic stimulation (TMS). LIFU can be focused at depth to reach the insula and ACC with high spatial precision. However, the effect of LIFU to the human dAI and dACC on autonomic control is unknown. To address this, the investigators will target the bilateral dAI and the dACC to assess how LIFU to each of these areas affects subjective report to different safe, reproducible autonomic challenges. These tasks are a cold pressor task, valsalva maneuver, and a deep breathing task.

Official Title
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Investigation of Low-intensity Focused Ultrasound to the Salience Network on Autonomic Function

Conditions
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Autonomic Dysfunction

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Does not meet exclusion criteria. Exclusion Criteria: The exclusion criteria below are regularly implemented in MRI, CT, and EEG experiments for the safety of the subjects and for data quality assurance. Claustrophobia (scanning environment may be uncomfortable). Contraindications to MRI: including pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants. Contraindications to CT: pregnancy Active medical disorder or treatment with potential central nervous system (CNS) effects (e.g. Alzheimer's) - History of neurologic disorder. (e.g. Parkinson's, Epilepsy, or Essential Tremor) History of head injury resulting in loss of consciousness for >10 minutes. History of alcohol or drug dependence (through self-report). History of cardiac disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: single arm, multi subject repeated measures
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Repeat measure LIFU and Sham<br>LIFU or Sham applied in repeat sessions to varying brain regions (dAI and dACC). | Device: Low-intensity focused ultrasound neuromodulation<br>* ultrasound transducer applying low intensity waveforms to targeted brain regions for neuromodulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sympathetic tone response - Heart Rate Variability (HRV) | Changes in HRV | through study completion, an average of 1 month | 
| Sympathetic tone response - Heart Rate (HR) | Changes in HR | through study completion, an average of 1 month | 
| Sympathetic tone response - Blood Pressure (BP) | Changes in BP (systolic and diastolic pressure) | through study completion, an average of 1 month | 
| Sympathetic tone response - Electrodermal Response (EDR) | Changes in EDR | through study completion, an average of 1 month | 
| Sympathetic tone response - Electroencephalography (EEG) | Changes in low and high frequency power | through study completion, an average of 1 month |