Ultrasound Brain Stimulation for Healthy Subjects

Overseen By Bin He, PhD

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

Trial Summary

What is the purpose of this trial?

Neuromodulation is a fast growing field that offers a wide range of applications for both understanding and treating the brain. Future research for non-invasive neuromodulation will need to elucidate the optimal frequency, duration, and intensity of stimulation for a variety of technologies and diseases. Closed loop stimulation is thus a promising research area that allows for responsive stimulation and real time symptom management. Our project is proposed to develop and test a novel noninvasive neuromodulation integrating transcranial focused ultrasound stimulation (tFUS) with electrophysiological source imaging (ESI-tFUS) to allow evidence-based neuromodulation for brain research and the management of brain conditions. Despite the recent developments and attention surrounding tFUS, relatively little is known about the mechanisms and optimal parameters of this stimulation technology. The addition of ESI neuroimaging, aimed at providing biomarkers to assess the effects of tFUS neuromodulation, could provide crucial necessary information regarding the neural response to the applied stimulation in real-time. In order for tFUS to be further developed and transformed into a robust neuromodulation technology, an integrated electrophysiological source-imaging-guided tFUS system to allow for individualized and responsive stimulation is needed. The purpose of this study is to develop and evaluate the proposed ESI-tFUS in human subjects using motor and somatosensory paradigms.

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 data supports the effectiveness of the treatment Transcranial Focused Ultrasound (tFUS) for brain stimulation?

Research shows that Transcranial Focused Ultrasound (tFUS) can precisely target and stimulate specific brain areas, potentially exciting or suppressing neural activity. It has been used successfully in treating conditions like movement disorders and psychiatric applications, offering a non-invasive alternative to traditional brain surgeries. ^{1 2 3 4 5}

How is the treatment Transcranial Focused Ultrasound (tFUS) unique compared to other treatments?

Transcranial Focused Ultrasound (tFUS) is unique because it is a non-invasive treatment that uses sound waves to precisely target and stimulate specific brain regions without surgery. It offers high spatial precision and can both excite and inhibit neural activity, making it different from other brain stimulation techniques. ^{1 6 7 8 9}

Research Team

Bin He, Ph.D.

Principal Investigator

Carnegie Mellon University

Eligibility Criteria

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

I am between 18 and 64 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 (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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI: a pilot study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound stimulation of human primary visual cortex. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection. [2023]