Ultrasound Brain Stimulation for Healthy Subjects

Overseen By Joshua Kosnoff

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Carnegie Mellon University

Must not be taking: Seizure threshold reducers

Disqualifiers: Significant illness, Neurologic disorder, Seizure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 2 years

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new brain stimulation method using sound waves, known as transcranial focused ultrasound, to better understand and potentially treat brain conditions. Researchers aim to determine the best use of this technology by testing both real and sham ultrasound on participants. They focus on observing the brain's real-time response to this stimulation. The trial seeks healthy volunteers without a history of serious medical or mental health issues. As an unphased trial, it offers participants the chance to contribute to groundbreaking research in brain health.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that lower the seizure threshold. It's best to discuss your specific medications with the study team.

What prior data suggests that this ultrasound brain stimulation is safe for healthy subjects?

Research has shown that transcranial focused ultrasound (tFUS) is generally safe at low power levels. Studies have found that this technique can alter the activity of specific brain areas without causing significant harm. Serious side effects are rare, though high power levels could pose risks like cell damage or bleeding. However, these risks are uncommon at the levels typically used in research.

In past studies, participants did not experience major issues with low-power tFUS. This method is considered safe and non-invasive, as it does not require surgery, for brain stimulation. It has also shown potential benefits for neurological and psychiatric disorders, as well as for pain and sleep problems.

Overall, tFUS is well-tolerated in humans, especially at the lower power levels typically used in studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because transcranial focused ultrasound offers a non-invasive way to stimulate the brain, which is different from traditional methods like medication or surgical procedures. This technique uses precise sound waves to target specific areas of the brain, potentially leading to fewer side effects and more accurate outcomes. By comparing real ultrasound with a sham version, researchers aim to understand its true impact on brain activity, opening doors to innovative treatments for various neurological conditions in the future.

What evidence suggests that this ultrasound brain stimulation is effective for neuromodulation?

Research has shown that transcranial focused ultrasound (tFUS) is a promising technique for stimulating the brain without surgery. Studies have found that it can precisely target specific brain areas, aiding both research and potential treatments. For instance, low-intensity tFUS has demonstrated positive effects in treating certain brain and mental health disorders. In this trial, participants will receive either a real ultrasound intervention or a sham ultrasound intervention. Although more research is needed to fully understand its benefits, early results suggest it could be a valuable tool for brain health. ^{4 6 7 8 9}

Who Is on the Research Team?

Bin He, Ph.D.

Principal Investigator

Carnegie Mellon University

Are You a Good Fit for This Trial?

This trial is for healthy volunteers aged 18-64 who can consent and communicate in English. It's not for those with a history of stroke, significant unconsciousness, seizures, pregnancy, or certain medical conditions. People taking seizure-lowering meds are also excluded.

Inclusion Criteria

Willing and able to provide written consent

Apparently healthy volunteers

Able to communicate in the English language

Exclusion Criteria

I have a serious illness or a mental/neurological condition.

I or someone in my family has had seizures.

I have lost consciousness for more than 10 minutes in the past year or needed rehab for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial focused ultrasound stimulation (tFUS) while undergoing motor and/or sensory tasks, monitored by EEG

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Focused Ultrasound

Trial Overview

The study tests a new non-invasive brain stimulation method combining transcranial focused ultrasound (tFUS) with electrophysiological source imaging (ESI). It aims to optimize tFUS parameters using real-time neuroimaging feedback.

How Is the Trial Designed?

Group I: Real Ultrasound Active Control 1 Intervention

The subjects will receive real ultrasound intervention.

Group II: Sham Ultrasound Placebo Group 1 Intervention

The subjects will receive sham ultrasound intervention.

Who Is Running the Clinical Trial?

Carnegie Mellon University

Lead Sponsor

Trials

80

Recruited

540,000+

Published Research Related to This Trial

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

Transcranial focused ultrasound (tFUS) is a promising non-surgical technique for neuromodulation that offers better spatial resolution compared to traditional electro and electromagnetic methods.

tFUS can effectively target sub-cortical brain structures non-invasively, and its combination with BOLD functional MRI allows for enhanced examination of brain activity in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. Leo Ai, ., Mueller, JK., Grant, A., et al.[2022]

In a study involving two rhesus macaques and thirteen Dorset sheep, transcranial focused ultrasound (FUS) neuromodulation was found to be safe, as no tissue damage was observed in the brain following treatment, even after multiple sessions.

The study confirmed that the FUS and MR-ARFI methods do not cause histologic abnormalities, indicating their potential for non-invasive brain treatment without harmful effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep. Gaur, P., Casey, KM., Kubanek, J., et al.[2021]

Transcranial focused ultrasound (FUS) can effectively stimulate the motor area of the brain in rats using lower acoustic intensities (4.9-5.6 W/cm²) with specific pulsing parameters, indicating its potential for safe brain stimulation.

The study found that pulsed sonication is more effective than continuous sonication for eliciting motor responses, suggesting that this method could be optimized for therapeutic applications while adhering to safety limits for biological tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters. Kim, H., Chiu, A., Lee, SD., et al.[2022]

Transcranial focused ultrasound (tFUS) effectively increases the activation volume of the thumb representation in the primary motor cortex (M1) during a finger tapping task, demonstrating its potential as a non-invasive neuromodulation technique.

The effects of tFUS are spatially restricted, as no significant changes were observed in the activation of other finger representations or connected motor regions, indicating a targeted mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI: a pilot study. Ai, L., Bansal, P., Mueller, JK., et al.[2023]

Low-intensity focused ultrasound (FUS) effectively suppressed responses to nociceptive heat stimulation in specific thalamic nuclei, indicating its potential as a neuromodulation tool for pain management.

The study revealed that this suppression altered the flow of information within nociceptive networks, suggesting that FUS can modulate how pain signals are processed in the brain, with implications for understanding thalamocortical connections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei. Mishra, A., Yang, PF., Manuel, TJ., et al.[2023]

Transcranial focused ultrasound (FUS) successfully stimulated the primary visual cortex in humans, activating not only the targeted area but also related brain regions involved in visual and cognitive processes, as confirmed by functional MRI.

No adverse effects were reported in participants, indicating that FUS is a safe method for non-invasive brain stimulation, with potential applications in neuroscience and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound stimulation of human primary visual cortex. Lee, W., Kim, HC., Jung, Y., et al.[2022]

MRI-guided focused ultrasound (FUS) can non-invasively excite specific brain areas in monkeys, leading to detectable changes in brain activity patterns similar to those seen with natural tactile stimulation.

The study reveals that FUS not only activates targeted neurons but also influences related brain regions differently than traditional tactile stimuli, suggesting a unique mechanism of neural activation and hemodynamic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection. Yang, PF., Phipps, MA., Newton, AT., et al.[2023]

A study involving 120 participants evaluated the safety of low intensity transcranial focused ultrasound (LIFU) for neuromodulation, finding no serious adverse effects and only mild to moderate symptoms reported by 7 participants, which were generally transient.

The symptom profile from LIFU was similar to other non-invasive brain stimulation methods, suggesting that LIFU is a safe option for neuromodulation with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. Legon, W., Adams, S., Bansal, P., et al.[2021]

Citations

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pubmed.ncbi.nlm.nih.gov

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A Randomized, Double-Blind, Sham-Controlled Clinical Trial

The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder.

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This review synthesizes animal and human research outcomes and offers an integrated description of the excitatory and inhibitory effects of tFUS.

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Low-intensity transcranial ultrasound stimulation shows therapeutic effects in neurological and psychiatric disorders.

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nature.com

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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.

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Compared to TMS and tDCS, tFUS provides greater spatial resolution and therefore can target brain structures with high precision, allowing for ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1935861X19303389

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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- ...

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A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. Wynn Legon,; Sarah ...

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Safety of Clinical Ultrasound Neuromodulation - PMC

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Transcranial focused ultrasound (tFUS) given at a low acoustic intensity has been shown to increase or suppress the excitability of region-specific brain areas.