There are a number of disorders of the brain that have limited treatment options, such as chronic pain, addiction, and major depression. A new technology has emerged in the last decade known as transcranial focused ultrasound, which can deliver focused acoustic signals through the skull to modulate brain activity over a small region, including structures deep in the brain. This has resulted in many ongoing clinical trials for various disorders, but there is still a lack of understanding of the optimal sonication parameters for increasing versus decreasing brain activity. The investigators aim to address this open question by sonicating the primary visual cortex and primary auditory cortex in human with a range of sonication parameters. These brain structures were chosen to target because they are expected to elicit perceptual responses in the subject (i.e., the subject will report visual and auditory perception during sonication), allowing the experimenters to infer directly the extent to which neural signals can propagate through the visual and auditory systems in a way that is sufficient to produce conscious perception. Such findings have applications not only in clinical treatments, but also in the fundamental science of the neural basis of sensory perception. Previous work has shown that sonicating the visual cortex in humans can elicit visual perception, but the ultrasonic system in prior work did not have the focusing capabilities that will be employed in this study. At the end of this study, the investigators will have determined the optimal sonication parameters that can elicit neural responses over a small volume over sensory cortex, which can be inferred from visual percepts being localized in space (e.g., a bright spot as opposed to a diffuse light), and auditory percepts that sound like pure tones rather than a broad set of frequencies (e.g., sounding like white noise or static).

This study will evaluate the effects of low-intensity transcranial focused ultrasound (tFUS) on brain activity in healthy adult volunteers. Transcranial ultrasound is a non-invasive technique that delivers acoustic energy through the skull to a small, targeted region of the brain. Unlike other forms of non-invasive brain stimulation, ultrasound can reach deep and superficial brain structures with millimeter-scale precision.

Transcranial ultrasound is currently being explored as a potential treatment for neurological and psychiatric conditions, including chronic pain, addiction, and depression. However, the optimal stimulation parameters for increasing versus decreasing brain activity in humans are not yet well established. The purpose of this study is to determine which ultrasound pulse parameters produce measurable excitation or suppression of brain activity in the human cortex.

The study will focus on two brain regions: the primary visual cortex and the primary auditory cortex. These regions were selected because stimulation of these areas may produce perceptual experiences, such as seeing flashes of light or hearing tones. These perceptual reports, together with brain recordings, allow researchers to directly assess how ultrasound affects neural activity.

Participants will complete three visits.

During Visit 1, participants will undergo informed consent, baseline testing of visual or auditory function, and magnetic resonance imaging (MRI). MRI scans will be used to identify each participant's individual brain anatomy and precisely localize the stimulation target.

During Visit 2, participants will undergo ultrasound stimulation while brain activity is recorded using electroencephalography (EEG). EEG is a non-invasive method that measures electrical signals from the scalp. Baseline brain responses to visual or auditory stimuli will be recorded before stimulation. Ultrasound will then be delivered in brief bursts while EEG continues to record brain activity. Participants may be asked to report any sensations experienced during stimulation. After stimulation, additional EEG recordings and behavioral tests will be performed to evaluate short-term effects.

Three different ultrasound pulse durations will be tested in randomized order. Each stimulation condition will consist of short bursts separated by rest periods. Total stimulation time will be limited, and rest intervals will be included between conditions.

During Visit 3, which will occur at least one week later, participants will repeat behavioral testing and undergo a follow-up structural MRI scan to confirm that no structural changes occurred.

The ultrasound intensities used in this study are below established U.S. Food and Drug Administration (FDA) safety limits for diagnostic ultrasound. The spatial peak pulse average intensity (Isppa) and spatial peak temporal average intensity (Ispta) will be maintained below FDA exposure limits, even before accounting for attenuation of the signal by the skull. Mechanical index (MI) values will also remain below recommended safety thresholds. Based on prior human studies involving thousands of participants, the risk of serious adverse effects is considered very low.

Potential risks include temporary scalp discomfort, mild skin irritation from ultrasound gel, or transient sensory effects such as light flashes or sounds. Although seizures have not been reported in human studies using these parameters, ultrasound does modulate brain activity, and a theoretical risk exists similar to other non-invasive brain stimulation methods. Participants will be monitored throughout all procedures.

There is no direct medical benefit to participants. However, the findings from this study may help guide the development of ultrasound-based treatments for neurological and psychiatric disorders and improve understanding of how targeted brain stimulation affects sensory perception.

Data collected will include MRI images, EEG recordings, behavioral performance measures, and participant-reported experiences. All data will be coded and stored securely in accordance with institutional policies.

The inclusion criteria for this study are as follows:

1. Healthy male and female adults aged 21-55.
2. No contraindications to magnetic resonance imaging (MRI) scans, such as claustrophobia.

The exclusion criteria for this study are as follows:

1. History of major medical, neurological (including peripheral nerve disease) or psychiatric illness.
2. History of vsacular conditions, predisposition to hemorrhage, or blood thinner medications
3. History of head trauma with loss of consciousness.
4. Use of sedatives, analgesics and agents that affect brain function.
5. Contraindications for exposure to the high magnetic field of MRI imaging
6. History of skin irritation from acoustic coupling materials such as a water-based gel and polyvinyl alcohol (PVA; a common household plastic bag material).
7. Vulnerable subpopulations (pregnant women, children, institutionalized individuals).
8. Use of excessive alcohol (e.g., no more than one can of beer or glass of wine) or strenuous exercise (e.g., no more than daily routine) on the day of the visit

Individual participant data will not be shared because this is a small, exploratory study in healthy volunteers, and there are no plans for public release of de-identified participant-level data. Results will be reported in aggregate form in scientific publications.