Low-intensity Focused Ultrasound and Autonomic Response

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

Studying the effects of Low Intensity Focused Ultrasound (LIFU) to the dorsal posterior insula (dPI) and dorsal anterior cingulate cortex (dACC) on autonomic control using a test to probe the autonomic system. A cold pressor task will be performed pre and post LIFU application. Physiologic recordings will be recorded throughout.

Study Overview

• Status: Enrolling by invitation
• Conditions: Autonomic Dysfunction
• Intervention / Treatment: Device: Low-intensity focused ultrasound neuromodulation; Device: Sham Low-intensity focused ultrasound

Detailed Description

Characterize the effect of LIFU to the bilateral dorsal posterior insula (dPI) and dorsal anterior cingulate cortex (dACC)) on autonomic control. The dPI is a critical brain area involved in autonomic function, being a core recipient of ascending pain and autonomic function. 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 dPI and dACC on autonomic control is unknown. To address this, the investigators will target the right dPI and the dACC to assess how LIFU to each of these areas affects autonomic responses and subjective report to the cold pressor task, a safe, reproducible autonomic challenge.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Fralin Biomedical Research Institute at VTC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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
• A current or prior use of any cardiac medication (e.g. beta blockers or other anti-arrhythmics)
• A history of diabetes mellitus or use of diabetic medications (e.g. metformin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dPI; LIFU to the dPI	Device: Low-intensity focused ultrasound neuromodulation; ultrasound transducer applying low intensity waveforms to targeted brain regions for neuromodulation.
Experimental: ACC; LIFU to the ACC	Device: Low-intensity focused ultrasound neuromodulation; ultrasound transducer applying low intensity waveforms to targeted brain regions for neuromodulation.
Sham Comparator: Sham; Sham LIFU application	Device: Sham Low-intensity focused ultrasound; sham application of ultrasound using blocking of the ultrasound waves of the transducer.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Virginia Polytechnic Institute and State University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): April 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias
• Other Study ID Numbers: 23-049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No