Causal Mechanisms of Odor-Guided Behavior in Humans

NCT07099092 | Not Yet Recruiting Early Phase 1

• 2 other identifiers: 10002358002358-DA
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Little is known about how different regions of the brain responsible for the human sense of smell guide behaviors. In this study, researchers use a technique called transcranial ultrasound stimulation (TUS) to learn how odors affect the brain and behavior. Objective: To learn more about how the human sense of smell works. Eligibility: Healthy people aged 18 to 45 years who are right-handed. Design: Participants can volunteer for up to 2 different experiments. Each experiment requires 5 visits, each about 1 week apart. Food, alcohol, and caffeine may be limited before visits. At the start of each visit, participants will answer questions about their health and how well they slept. Their sense of smell will be assessed. Some visits may include tasks on a computer: While doing these tasks, participants may be asked to smell different odors, look at pictures, and listen to sounds. They will wear devices to track breathing, blood pressure, pulse, and other body responses to the tasks. Some visits may include TUS: TUS uses ultrasound waves to briefly change brain activity. A gel will be applied to the scalp and hair, and a device will be placed against the participant s head. Participants may feel a tapping, pulling, and/or warm sensation on the skin underneath the device. They may also feel a twitch in their face, neck, arm, or leg muscles. Participants will do tasks before and after TUS. Some visits will include functional magnetic resonance imaging (fMRI) scans. fMRI uses magnet and radio waves to capture images of the activity inside the brain. Participants will lie on a table that slides into a tube. They will perform tasks inside the scanner.

Conditions

Normal Physiology

Keywords

Behavioral Tasks; Decision Making; fMRI; TUS

Outcome Measures

Primary Outcomes (1)

• Task Performance<TAB>

  Responses on behavioral tasks

  Immediately after TUS

Secondary Outcomes (2)

• task-based fMRI

  Immediately after TUS

• Report of symptoms

  before, during and after TUS

Study Arms (2)

Experiment 1

EXPERIMENTAL

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

Device: TUS PirC; Device: TUS Sham

Experiment 2

EXPERIMENTAL

TUS targeting amygdala or sham TUS before olfactory conditioning task

Device: TUS Amy; Device: TUS Sham

Interventions

TUS Amy DEVICE

120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting amygdala

Experiment 2

TUS Sham DEVICE

120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting white matter

Experiment 1; Experiment 2

TUS PirC DEVICE

120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting piriform cortex

Experiment 1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet the following criteria:
• Willingness to comply with all study procedures and availability for the duration of the study.
• Aged 18-45 years old. Justification: Many neural processes change with age, and these changes could introduce unwanted variability in the measured signals.
• 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.
• Right-handed.

You may not qualify if:

• Individuals who meet any of the following criteria will be excluded from participation:
• Any neurological disorder that would increase seizure risk from TUS such as stroke, brain lesions, previous neurosurgery, epilepsy, any history of seizure or fainting episode of unknown cause, frequent severe headache, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than one month. The MAI will also retain discretion to exclude based on a history of a neurological illness or trauma that may compromise safety or data integrity.
• Predisposition to seizures (e.g., first-degree family history of potentially hereditary epilepsy, etc.).
• Current use (any use in the past week, daily use for more than one week within past 3 months) of any investigational drug or of any medications with psychotropic (e.g., benzodiazepines, etc.), or anti or pro-convulsive action. This will be determined at the discretion of the MAI.
• Unable to undergo MRI, or TUS due to certain metallic or magnetic devices or implants in the body, claustrophobia, or other reasons.
• History of noise-induced hearing loss or tinnitus.
• Recent history (within past 12 months) of learning disability, major DSM-5 psychiatric disorder including major affective disorder, ADHD, obsessivecompulsive disorder, schizophrenia, or PTSD. This will be determined at the discretion of the MAI.
• 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.
• Daily nicotine, alcohol, or drug use (excluding caffeine) for at least 4 continuous weeks within the past 12 months.
• Participation in any neuromodulation (e.g., TMS, TUS, tDCS, tACS, etc.) session (excluding the current protocol) in the past two weeks.
• History of anaphylaxis, e.g., due to severe asthma, and/or food and non-food allergies (e.g., latex, detergents, soap, etc.).
• History of significant chronic obstructive pulmonary disease (COPD) as increased levels of carbon dioxide may increase the susceptibility to cavitation and related tissue damage.
• Uncorrected impairments in visual acuity severe enough to affect task participation.
• Non-English speaking. Justification: Data integrity of some of the behavioral tasks used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing TUS and MRI procedures. The inability to effectively communicate TUS and MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants.
• Serious skin disease or serious skin allergy on the hands or head. Justification: Gel will be applied to the skin on both head and hands, for transducer coupling and electrode placement, respectively. Allergic or adverse reactions to such treatment need to be ruled out.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

Study Officials

• Thorsten Kahnt, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NIDA IRP Screening Team

CONTACT

(800) 535-8254; researchstudies@nida.nih.gov

Thorsten Kahnt, Ph.D.

CONTACT

(667) 312-5175; thorsten.kahnt@nih.gov

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 1, 2025
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): July 14, 2035
• Study Completion (Estimated): July 14, 2035
• Last Updated: April 16, 2026

Record last verified: 2026-01-05

Locations

US (1)