Low-Intensity Focused Ultrasound for Memory Enhancement

Overseen By Wynn Assistant Professor, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, Neurologic disorder, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how noninvasive brain stimulation might improve memory. Participants will receive low-intensity focused ultrasound (LIFU) treatments, which use sound waves to gently alter brain activity, and researchers will closely monitor their reactions. The study includes different groups receiving either a real or a sham treatment to compare effects. It is ideal for English-speaking individuals without a history of neurological disorders or metal implants. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research in memory enhancement.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have an active medical disorder or are undergoing treatment that affects the central nervous system, you may not be eligible to participate.

What prior data suggests that this noninvasive brain stimulation technique is safe for memory enhancement?

Studies have shown that low-intensity focused ultrasound (LIFU) is generally safe for humans. Research indicates that transcranial ultrasound, including LIFU, is a non-invasive method to affect brain activity and is well-tolerated. Reviews of its use reveal that participants reported only minor side effects, usually mild and temporary, such as slight discomfort or a mild headache.

One study assessed LIFU's safety by observing participants' symptoms and brain health. The results were reassuring, with no major negative effects reported. These findings suggest that LIFU is a promising and safe option for brain stimulation, making it a good choice for those considering joining clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Low-Intensity Focused Ultrasound (LIFU) for memory enhancement because it offers a non-invasive way to potentially improve memory. Unlike current treatments, such as medications that often come with side effects, LIFU uses sound waves to stimulate specific brain areas without surgery or drugs. This technique could provide a safer and more targeted option for patients, with the possibility of fewer side effects. Additionally, LIFU's unique mechanism of action—using ultrasound to directly influence brain activity—sets it apart from traditional approaches, potentially leading to faster results in improving memory function.

What evidence suggests that low-intensity focused ultrasound could be effective for memory enhancement?

Research has shown that low-intensity focused ultrasound (LIFU) might improve memory and thinking skills. In one early study, patients experienced slight improvements in memory and overall brain function after LIFU treatment. This trial will explore various LIFU parameter sets to assess their impact on memory enhancement. The method uses sound waves to alter brain activity without surgery. It offers a noninvasive way to potentially boost memory, particularly in brain areas related to forming memories. So far, no serious side effects have been reported, making it a promising area of study for enhancing memory. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals of any ethnicity interested in participating in a study that explores noninvasive brain stimulation's effects on memory. Participants will undergo MRI and CT scans, receive low-intensity focused ultrasound treatments, and complete various tests to monitor their brain activity and memory functions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment and Imaging

Participants undergo structural and functional imaging with MRI and CT scans, and complete a questionnaire battery

1 session

1 visit (in-person)

LIFU Stimulation or Sham

Participants receive LIFU stimulation or sham across sessions 2-8, with memory tasks, neuropsychological assessments, EEG recording, and physiological measures

6 sessions over 6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-intensity Focused Ultrasound

Trial Overview The study is testing the impact of low-intensity focused ultrasound (LIFU) on human memory by comparing it with a sham treatment (no real treatment). It involves monitoring changes in brain signals through MRI or EEG, as well as tracking vital signs during neuropsychological tasks.

How Is the Trial Designed?

Group I: LIFU 7 Experimental Treatment 1 Intervention

LIFU stimulation with parameter set 7 visit with memory tasks and neuropsychological assessments.

Group II: LIFU 6 Experimental Treatment 1 Intervention

LIFU stimulation with parameter set 6 visit with memory tasks and neuropsychological assessments.

Group III: LIFU 5 Experimental Treatment 1 Intervention

LIFU stimulation with parameter set 5 visit with memory tasks and neuropsychological assessments.

Group IV: LIFU 4 Experimental Treatment 1 Intervention

LIFU stimulation with parameter set 4 visit with memory tasks and neuropsychological assessments.

Group V: LIFU 3 Experimental Treatment 1 Intervention

LIFU stimulation with parameter set 3 visit with memory tasks and neuropsychological assessments.

Group VI: LIFU 2 Experimental Treatment 1 Intervention

LIFU stimulation with parameter set 2 visit with memory tasks and neuropsychological assessments.

Group VII: LIFU 1 Experimental Treatment 1 Intervention

LIFU stimulation with parameter set 1 visit with memory tasks and neuropsychological assessments.

Group VIII: Sham LIFU Placebo Group 1 Intervention

Sham LIFU stimulation visit with memory tasks and neuropsychological assessments.

Low-intensity Focused Ultrasound is already approved in United States, European Union for the following indications:

Approved in United States as LIFU for:

• Research purposes for neurological conditions such as depression, addiction, and pain management

Approved in European Union as LIFU for:

• Research purposes for neurological conditions such as depression, addiction, and pain management

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Published Research Related to This Trial

Low-intensity focused ultrasound (LIFUS) is a promising noninvasive technique that can modulate human brain activity, showing effects like suppressing cortical evoked potentials and altering sensory/motor task outcomes in studies involving human subjects.

The proposed mechanisms of LIFUS include cavitation and direct effects on neural ion channels, suggesting it could be developed for non-surgical treatments of neurological disorders, although optimal protocols are still being refined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. Fomenko, A., Neudorfer, C., Dallapiazza, RF., et al.[2019]

Transcranial focused ultrasound (tFUS) can precisely target specific brain areas with low acoustic intensity, effectively modulating brain excitability and potentially promoting neural plasticity for neurorehabilitation.

The review highlights the excellent safety profile of tFUS, but emphasizes the need for new safety guidelines and recommendations for its use in healthy volunteers and clinical settings, based on a comprehensive analysis of acoustic parameters and their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. Lee, W., Weisholtz, DS., Strangman, GE., et al.[2023]

The dual-crossed transducer system achieved high spatial resolution in targeting small brain regions in mice, with a focal volume of under 0.52 μm³ and a focal diameter of 1 mm, making it effective for precise neuromodulation.

In vivo experiments demonstrated successful brain stimulation in wild-type mice, evidenced by observable movements, confirming the system's capability for noninvasive and specific targeting of brain circuits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound stimulation with high spatial resolution. Kim, S., Jo, Y., Kook, G., et al.[2021]

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]

In a study of 372 women with symptomatic uterine fibroids who underwent MR-HIFU, the overall rate of adverse events (AEs) was low at 8.9%, with no major AEs reported, indicating that MR-HIFU is a safe treatment option.

The only significant risk factor for AEs was the treatment of type II uterine fibroids, suggesting that while MR-HIFU is generally safe, certain types of fibroids may carry a higher risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence of adverse events after magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) therapy in symptomatic uterine fibroids-a retrospective case-control study. Kociuba, J., Łoziński, T., Zgliczyńska, M., et al.[2023]

Microfocused Ultrasound with Visualization (MFU-V) has a well-established safety profile, showing only mild and transient side effects like tenderness and redness, with rare adverse events typically linked to improper technique.

When used correctly, MFU-V treatments are safe, with most side effects resolving quickly and without lasting effects, indicating its efficacy in cosmetic dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. Hitchcock, TM., Dobke, MK.[2022]

Low intensity focused ultrasound (LIFU) is a promising non-invasive technology that can precisely modulate brain activity, offering a new approach to studying and potentially treating psychiatric illnesses.

LIFU has been shown to safely affect both cortical and subcortical brain regions, distinguishing it from other neuromodulatory techniques due to its spatial precision and reversible effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. Arulpragasam, AR., van 't Wout-Frank, M., Barredo, J., et al.[2022]

High-density gel polymer matrices are effective couplants for low-intensity focused ultrasound (LIFU) neuromodulation, showing low acoustic attenuation (3.3%) and minimal beam distortion, making them suitable for clinical use.

The study highlights the importance of using standardized methods for preparing these gels to ensure consistent performance, as factors like thickness and de-gassing can significantly affect acoustic transmission and pressure attenuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. Strohman, A., In, A., Stebbins, K., et al.[2023]

A systematic review of 33 studies on low-intensity transcranial focused ultrasound stimulation (TFUS) indicates that adverse effects are very rare, with most studies showing no significant negative outcomes even when safety limits were exceeded.

However, at high stimulation intensities, TFUS can potentially cause serious issues like hemorrhage, cell death, and unintended blood-brain barrier opening, highlighting the need for further research to establish clear safety guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Pasquinelli, C., Hanson, LG., Siebner, HR., et al.[2020]

Low intensity focused ultrasound (LiFUS) can effectively disrupt the blood-brain barrier (BBB) in a dose-dependent manner, with increased tracer uptake in the brain observed when using higher microbubble and cavitation doses.

The timing of tracer administration is crucial; the highest accumulation of small solutes occurs when administered just before LiFUS, but significant uptake is also seen up to 6 hours post-treatment, indicating a biphasic response in BBB permeability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model. Arsiwala, TA., Sprowls, SA., Blethen, KE., et al.[2023]

Citations

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A pilot clinical study of low-intensity transcranial focused ... Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05417555?cond=Alzheimer%20Disease&term=focused%20ultrasound&aggFilters=status:not%20rec&rank=2

Low Intensity Focused Ultrasound for Mild Cognitive ... The goal of this study is to investigate whether Low Intensity Focused Ultrasound Pulsation (LIFUP) targeting a part of the brain involved in memory will ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1094715924006627

A Comprehensive Review of Low-Intensity Focused ... In this study, we provide a review of the most recent LIFU literature covering three key domains: 1) the history of focused ultrasound technology, comparing it ...

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Alzheimer's Disease Focused ultrasound is a noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with ...

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Transcranial Focused Ultrasound: A New Frontier for Non- ... Transcranial focused ultrasound (tFUS) is an innovative non-invasive neuromodulation technique that uses low-intensity ultrasound waves to modulate brain ...

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Safety of Clinical Ultrasound Neuromodulation - PMC Transcranial ultrasound holds much potential as a safe, non-invasive modality for navigated neuromodulation, with low-intensity focused ultrasound (FUS) and ...

7. nature.com nature.com/articles/s41598-020-62265-8

A retrospective qualitative report of symptoms and safety ... We provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of ...

8. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.825802/full

Low Intensity Focused Ultrasound for Non-invasive and ... This article describes an emerging non-invasive neuromodulatory technology, called low intensity focused ultrasound (LIFU).