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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This research project is examining the effects of noninvasive brain stimulation on human memory. This study will help to better understand noninvasive brain stimulation techniques that may have the potential to aid in memory dysfunction. Subjects will undergo a magnetic resonance imaging (MRI) and a computed tomography (CT) scan, to take pictures of their brain and skull. They will receive noninvasive brain stimulation using low-intensity focused ultrasound (LIFU) sound waves, to temporarily change brain activity. Their brain signals (MRI or EEG) will be monitored to measure changes in their brain signals. Their heart rate, blood pressure, respiratory rate, eye movement and skin moisture will be monitored as well. They will complete neuropsychological batteries and memory tasks. They will complete questionnaires.

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 data supports the effectiveness of this treatment?

Research shows that low-intensity focused ultrasound (LIFU) can safely change brain activity without surgery, which might help with memory and other brain functions. It's been used to affect brain areas involved in psychiatric conditions, showing promise for non-invasive brain treatments. ^{1 2 3 4 5}

Is Low-Intensity Focused Ultrasound (LIFU) safe for use in humans?

Research on Low-Intensity Focused Ultrasound (LIFU) for brain stimulation in humans shows it is generally safe, with no serious side effects reported. Some participants experienced mild symptoms like neck pain, attention problems, muscle twitches, and anxiety, which were similar to other non-invasive brain stimulation methods and resolved quickly. ^{6 7 8 9 10}

How is the treatment Low-Intensity Focused Ultrasound (LIFU) for memory enhancement different from other treatments?

Low-Intensity Focused Ultrasound (LIFU) is unique because it is a non-invasive treatment that can precisely target deep brain areas with sound waves, unlike other methods that may require surgery or have less precision. Its effects are reversible, allowing for safe modulation of brain activity, which is not typically possible with other brain stimulation techniques. ^{1 2 4 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. [2023]

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

Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. [2019]

4. Iran pubmed.ncbi.nlm.nih.gov

A Review on Brain Stimulation Using Low Intensity Focused Ultrasound. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model. [2023]

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

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

7. England 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. [2023]

8. United States 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. [2020]

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

Review of the safety profile for microfocused ultrasound with visualization. [2022]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. [2023]

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

Transcranial focused ultrasound stimulation with high spatial resolution. [2021]

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

Comparison of Transcranial Focused Ultrasound and Transcranial Pulse Stimulation for Neuromodulation: A Computational Study. [2022]