TUS Interventions for Odor-Guided Behavior

Overseen By NIDA IRP Screening Team

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: Psychotropics, Anticonvulsants

Disqualifiers: Neurological disorders, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the brain processes smells and how these affect behavior. Researchers will use transcranial ultrasound stimulation (TUS), a technique that uses sound waves to temporarily change brain activity, to study brain responses to different odors. Participants will complete tasks involving smells, images, and sounds, and may undergo brain imaging. The study seeks healthy, right-handed individuals with no known issues with their sense of smell.

As an Early Phase 1 trial, this research focuses on understanding how TUS affects brain activity in response to odors, offering participants a chance to contribute to groundbreaking scientific knowledge.

Do I need to stop taking my current medications to join the trial?

The trial requires that you do not use any medications with psychotropic effects or those that affect seizures within the past week or daily for more than one week in the past three months. If you are taking such medications, you may need to stop them to participate.

What prior data suggests that transcranial ultrasound stimulation (TUS) is safe for odor-guided behavior studies?

Previous studies have examined the safety and effects of transcranial ultrasound stimulation (TUS) on the brain. For TUS targeting the amygdala (TUS Amy), research shows that side effects are very rare. High levels of stimulation might pose risks like bleeding or cell damage, but these are uncommon, especially with low-intensity settings.

For TUS targeting the Piriform Cortex (TUS PirC), safety data is reassuring. Many studies report no side effects among participants. While some effects have been noted in a few studies, they are not common.

Overall, both TUS Amy and TUS PirC are considered well-tolerated, particularly at lower intensities. This early phase study aims to ensure the treatment is safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these TUS interventions for odor-guided behavior because they offer a non-invasive approach to potentially enhance olfactory-related tasks. Unlike traditional treatments that might rely on medications or behavioral therapies, TUS (transcranial ultrasound stimulation) targets specific brain regions like the amygdala and piriform cortex. This technique uses sound waves to modulate brain activity, which could lead to more precise and immediate effects on how we perceive and react to smells. This innovative method might provide new insights into brain function and behavior, paving the way for novel therapeutic strategies.

What evidence suggests that this trial's TUS interventions could be effective for odor-guided behavior?

Research shows that transcranial ultrasound stimulation (TUS) can focus on specific brain areas to influence behavior. In this trial, participants will receive either TUS Amy, which targets the amygdala, TUS PirC, which targets the PirC, or a sham TUS as a control. Studies have found that TUS Amy can target the amygdala, a brain region involved in mood and anxiety, suggesting it might help manage emotional responses. Research has explored how TUS PirC can affect decision-making related to smell, examining how odors influence choices and reactions. Both uses of TUS are still under investigation, but they offer a promising view of how brain stimulation could change behavior and perception. ^{1 6 7 8 9}

Who Is on the Research Team?

Thorsten Kahnt, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

This trial is for healthy right-handed individuals aged 18 to 45 who are interested in how the human sense of smell influences behavior. Participants will be required to attend multiple sessions, possibly abstain from certain foods, alcohol, and caffeine, and undergo various non-invasive procedures.

Inclusion Criteria

Willingness to comply with all study procedures and availability for the duration of the study

In good general health based on the assessment of the Medical Advisory Investigator (MAI)

Agreement to adhere to Lifestyle Considerations throughout study duration. Consent signature will be documentation of meeting this criterion

Exclusion Criteria

History of noise-induced hearing loss or tinnitus

Pattern of alcohol and drug use in the past 12 months that is indicative of harmful use, loss of control over use, or physical dependence

Participation in any neuromodulation (e.g., TMS, TUS, tDCS, tACS, etc.) session (excluding the current protocol) in the past two weeks

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experiment 1

Participants undergo TUS targeting PirC or sham TUS before olfactory perceptual decision making task

5 weeks

5 visits (in-person)

Experiment 2

Participants undergo TUS targeting amygdala or sham TUS before olfactory conditioning task

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after TUS

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TUS Amy
• TUS PirC
• TUS Sham

Trial Overview Researchers are testing the effects of transcranial ultrasound stimulation (TUS) on brain regions linked to smell. The study involves TUS targeting different brain areas (PirC, Amy), compared with a sham procedure. Tasks during visits include computer activities while smelling odors and undergoing body response tracking.

How Is the Trial Designed?

Group I: Experiment 2 Experimental Treatment 2 Interventions

TUS targeting amygdala or sham TUS before olfactory conditioning task

Group II: Experiment 1 Experimental Treatment 2 Interventions

TUS targeting PirC or sham TUS before olfactory perceptual decision making task

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12135807/

Transcranial ultrasound stimulation parameters for ... This study explored the relationship between TUS stimulation parameters and treatment outcomes using a systematic review and multiple linear regression analysis ...

2. withpower.com withpower.com/trial/early-phase-1-normal-physiology-8-2025-dab9d

TUS Interventions for Odor-Guided Behavior In this study, researchers use a technique called transcranial ultrasound stimulation (TUS) to learn how odors affect the brain and behavior.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06722339

Targeted Circuit-Based Transcranial Focused Ultrasound ... This study explores the potential of transcranial ultrasound stimulation (TUS) as an innovative therapeutic approach for individuals with ...

4. fusfoundation.org fusfoundation.org/posts/clinical-trial-results-focused-ultrasound-neuromodulation-improves-mood-anxiety-and-trauma-related-disorders/

Clinical Trial Results The researchers successfully targeted the left amygdala, which is known to be hyperactive in mood and anxiety disorders. The results from the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40275098/

a double-blind sham-controlled target engagement study and ... Low-intensity transcranial focused ultrasound amygdala neuromodulation: a double-blind sham-controlled target engagement study and unblinded ...

6. nature.com nature.com/articles/s41380-025-03033-w

Low-intensity transcranial focused ultrasound amygdala ... tFUS is a non-invasive technique for direct subcortical neuromodulation, but its safety, feasibility, and promise as a potential treatment is largely unknown.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X19303389

Safety of transcranial focused ultrasound stimulation Adverse effects of TFUS were very rare. At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood- ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9879416/

Safety Review and Perspectives of Transcranial Focused ... This review aims to provide safety information and perspectives of tFUS brain stimulation. First, the acoustic parameters most relevant to ...

9. mghpsychnews.org mghpsychnews.org/transcranial-focused-ultrasound/

Transcranial Focused Ultrasound: A New Frontier for Non- ... The results showed that individuals receiving active tFUS exhibited decreased activation of the amygdala during a fear-inducing task, as ...