Causal Mechanisms of Odor-Guided Behavior in Humans

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.

Study Description: Primary olfactory cortex has been implicated in a variety of odorguided behaviors in both animal models and humans. However, direct causal evidence for the functional role of different primary olfactory regions in humans is currently missing, due to the lack of non-invasive neuromodulation methods that can effectively target deep brain regions. With the recent advancement of transcranial focused ultrasound stimulation (TUS), this challenge can now be overcome. The goal of this protocol is to use TUS to temporarily modulate activity in primary olfactory cortex and thereby assess its contribution to olfactory function. Objectives: The primary objective is to determine the causal contribution of primary olfactory brain regions to olfactory functions. The secondary objective is to 1) evaluate the neural mechanisms by which these brain regions support these olfactory functions, and 2) assess the safety profile of TUS. Endpoints: The primary endpoint is to determine if TUS of olfactory cortices alters olfactory function. The secondary endpoints are to 1) evaluate whether TUS changes neural activity in olfactory regions and 2) assess the degree to which TUS elicits unwanted side effects in healthy adult participants.