Dose effects of low-intensity focused ultrasound on deep brain pathways

Dose-Dependent Functional Connectivity Effects of Low-Intensity Focused Ultrasound Applied to Deep White Matter Tracts in Humans

This project will test whether different doses of low‑intensity focused ultrasound change deep brain connections in healthy adults.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Laureate Institute for Brain Research, Inc. (other)
• Locations: 1 site (Tulsa, Oklahoma)
• Trial ID: NCT07099950 on ClinicalTrials.gov

What this trial studies

Low‑intensity focused ultrasound (LIFU) is a noninvasive method to modulate deep brain structures with anatomical precision. In this randomized study of 60 healthy adults, participants will receive one of two LIFU dose regimens targeted to deep white‑matter tracts, including tracts traversing the anterior limb of the internal capsule, with resting‑state fMRI used to measure changes in functional connectivity before and after sonication. The protocol varies both intensity and sonication duration to define dose–response effects on axonal conduction and circuit‑level connectivity. Results are intended to clarify how LIFU alters large‑scale brain networks and to guide future clinical applications in psychiatric disorders.

Who should consider this trial

Good fit: Healthy adults aged 18–65 with BMI 17–38 kg/m2, low anxiety and depression scores, fluent in English, able to give informed consent and undergo MRI, and not pregnant are ideal candidates.

Not a fit: People with active psychiatric illness or suicidal ideation, inability to consent, or contraindications to MRI (and pregnant individuals) are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this could provide a precise, noninvasive way to modulate deep brain circuits that may inform new treatments for psychiatric conditions.

How similar studies have performed: Preclinical data and early human work show LIFU can modulate gray‑matter targets and a recent pilot at the anterior limb of the internal capsule demonstrated target engagement, but formal dose–response data for white‑matter tracts remain limited.

Eligibility criteria

Inclusion Criteria:

* Age 18 to 65 years.
* Body mass index 17-38 kg/m2.
* Fluent English speaker, capable of providing written informed consent.
* Overall Anxiety Severity and Impairment Scale \<8 and Patient Health Questionnaire-9 \<10
* A person of childbearing potential must have a negative urine pregnancy test at screening
* Consent that random observations of pathology are possible (e.g., brain abnormality seen during imaging).

Exclusion Criteria:

* Inability to provide informed consent including medical, psychiatric, or other conditions that restrict the patient's following abilities: to interpret the study information, to give informed consent, to adhere to the rules of the protocol, or complete the study.
* No telephone or easy access to telephone
* Has active suicidal ideation (as measured by Suicide-Risk-Assessment-C-SSRS "Yes" answers to items 3, 4, or 5 Suicidal Ideation-Past 1 month section, or any "Yes" answer to any of the items of Suicidal Behavior-Past 3 months section), or any suicide attempt in the last 3 months
* Has positive test result(s) for alcohol of abuse (including methadone, opiates, cocaine, amphetamine/methamphetamine and ecstasy), or substance use disorder including alcohol, stimulants, sedatives, and cannabis exceeding mild severity in the last 6 months
* Has a lifetime APA Diagnostic and Statistical Manual of Mental Disorders (DSM)-5th edition including major depression, generalized anxiety disorder, specific phobias, panic disorder, post-traumatic stress disorder, schizophrenia spectrum and other psychotic disorders, obsessive-compulsive disorder, or bipolar disorder.
* Benzodiazepines or anticonvulsants in the 7 days prior to participation.
* MRI contradictions as detected by the MRI Safety Screen including claustrophobia and unwillingness and inability to complete scans (e.g., unable to lie on one's back for 60 mins.
* Clinical history of relevant structural pathology of the central nervous system, including Parkinson's disease, multiple sclerosis, and brain malignant neoplasia.
* History of unstable liver or renal insufficiency; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, hematological, rheumatological, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit or confound the protocol-specified assessments, including uncontrolled diabetes mellitus (ss evidenced by fasting glycemia ≥ 120 mg/dL or hemoglobin A1c ≥ 6.5%) or hypertension (as evidenced by two consecutive readings ≥ 140/90 mmHg) to ensure medical stability throughout this longitudinal study.
* Moderate-to-severe traumatic brain injury or any other clinical neurocognitive disorder.
* Clinical history of at least minor neurocognitive disorder of any origin.
* Prescription of a medication outside of the accepted range, as determined by best clinical practices and current research.
* Use of any psychotropic medication.
* Unwillingness or inability to complete any major aspects of the study protocol.
* Prior neurosurgery.
* Non-correctable vision or hearing.

Where this trial is running

Tulsa, Oklahoma

• Laureate Institute for Brain Research — Tulsa, Oklahoma, United States (RECRUITING)

Study contacts

• Study coordinator: Salvador M Guinjoan, MD, PhD

Conditions: Healthy Controls, Low-Intensity Focused Ultrasound, Functional Connectivity