Transcranial Ultrasonic Neuromodulation of Primary Visual Cortex and Primary Auditory Cortex in Humans

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers; no Condition, Basic Science
• Intervention / Treatment: Device: Transcranial Focused Ultrasound Stimulation; Device: Electroencephalography; Device: Magnetic Resonance Imaging

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel K Freeman, Ph.D.; Phone Number: 617-877-7145; Email: Daniel.Freeman@ll.mit.edu

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02139
      • Massachusetts Institute of Technology - McGovern Institute for Brain Research
      • Contact: Daniel K Freeman, Ph.D.; Phone Number: 617-877-7145; Email: Daniel.Freeman@ll.mit.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: Transcranial Focused Ultrasound Stimulation; Participants complete three visits. Visit 1 includes informed consent, baseline visual or auditory testing, and magnetic resonance imaging (MRI) for target localization. Visit 2 includes electroencephalography (EEG) recording and low-intensity transcranial focused ultrasound (tFUS) delivered to either primary visual cortex or primary auditory cortex (each participant receives one target only). Three ultrasound pulse durations are delivered in randomized order while EEG and behavioral responses are measured before, during, and after stimulation. Visit 3 (≥1 week later) includes repeat behavioral testing and a follow-up structural MRI.

Device: Transcranial Focused Ultrasound Stimulation; Low-intensity transcranial focused ultrasound delivered to either the primary visual cortex or primary auditory cortex using a research ultrasound system. Three pulse durations are tested in randomized order during a single study session while brain activity and behavioral responses are measured.; Other Names: Low-Intensity Focused Ultrasound (LIFU); Device: Electroencephalography; Noninvasive recording of brain electrical activity from scalp electrodes before, during, and after ultrasound stimulation.; Other Names: EEG; Device: Magnetic Resonance Imaging; Structural and functional magnetic resonance imaging used for anatomical localization of stimulation targets and follow-up safety assessment.; Other Names: MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sensory-evoked cortical response measured by electroencephalography	Change in peak-to-peak amplitude (µV) of sensory-evoked potentials recorded from scalp electroencephalography (EEG) over the targeted cortical region (visual or auditory cortex, depending on stimulation condition) during and after transcranial focused ultrasound stimulation, relative to baseline (pre-stimulation).	Measured during Visit 2 (baseline, during stimulation, immediately post-stimulation, and 15-20 minutes post-stimulation)
Change in visual detection threshold	Change in visual sensitivity thresholds measured using the visual field analyzer, quantified as detection threshold before and after transcranial focused ultrasound stimulation.	Baseline (Visit 1); pre-stimulation (Visit 2); immediately after stimulation (Visit 2); and 1 week after stimulation (Visit 3)
Change in auditory tone detection threshold	Change in auditory detection thresholds measured using commercial audiometry system (e.g., WAHTS Hearing), quantified as minimum detectable sound level (dB HL) across frequencies (250 Hz-8 kHz) before and after transcranial focused ultrasound stimulation.	Baseline (Visit 1); pre-stimulation (Visit 2); immediately after stimulation (Visit 2); and 1 week after stimulation (Visit 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant-reported perceptual intensity measured by numeric rating scale during transcranial focused ultrasound stimulation	Participant-reported sensory percepts occurring during transcranial focused ultrasound stimulation (e.g., visual flashes or auditory tones), quantified using a numeric rating scale (0-10), where 0 indicates no percept and 10 indicates maximum perceived intensity. Presence or absence of percepts will also be recorded.	During each stimulation block (each approximately 6-7 minutes; up to 20 minutes total) at Visit 2
Number of participants with new structural brain abnormalities on MRI following transcranial focused ultrasound stimulation	Structural magnetic resonance imaging (MRI) (T1-weighted and susceptibility-weighted imaging) will be evaluated by a qualified radiologist to identify any new or worsened structural abnormalities in the sonicated brain region compared to baseline imaging. The outcome will be reported as the number of participants with identified abnormalities.	1 week after stimulation (Visit 3)

Collaborators and Investigators

• Sponsor: Massachusetts Institute of Technology
• Collaborators: MIT Lincoln Laboratory

Publications and helpful links

General Publications

• Freeman DK, Odegaard B, Yoo SS, Michel M. Transcranial focused ultrasound for identifying the neural substrate of conscious perception. Neurosci Biobehav Rev. 2026 Jan;180:106485. doi: 10.1016/j.neubiorev.2025.106485. Epub 2025 Nov 19.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): November 18, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Non-invasive Brain Stimulation; Transcranial Focused Ultrasound; Ultrasound Neuromodulation
• Additional Relevant MeSH Terms: Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Diagnostic Techniques, Neurological; Electrodiagnosis; Magnetic Resonance Imaging; Electroencephalography
• Other Study ID Numbers: 2507001708; TI25-5201 (Other Grant/Funding Number: MIT Lincoln Laboratory)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No