Transcranial Magnetic Stimulation for Memory Improvement

Overseen By Anna Wilhelm, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Nebraska

Must not be taking: Seizure threshold-lowering

Disqualifiers: Metal implants, Major illness, Epilepsy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether transcranial magnetic stimulation (TMS), a non-invasive treatment, can boost memory. It focuses on healthy young adults, healthy older adults, and older adults with amnestic mild cognitive impairment (aMCI), a condition that can lead to Alzheimer's. Participants will experience two different setups: one begins with TMS followed by a sham version, and the other does it in reverse. Suitable candidates for this trial are right-handed, fluent in English, and able to sit still for TMS sessions, with no history of neurological issues other than aMCI. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on memory enhancement.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using medication that lowers the seizure threshold, you may not be eligible to participate.

What prior data suggests that transcranial magnetic stimulation is safe for memory improvement?

Research shows that targeted transcranial magnetic stimulation (TMS) is generally safe. Studies have found that repetitive TMS (rTMS) does not cause seizures or memory loss, unlike treatments such as electroconvulsive therapy. It also doesn't require anesthesia, making it less risky and more comfortable for participants.

Additionally, rTMS has been tested in people with Alzheimer’s disease and is considered safe, being well-tolerated without causing serious side effects. A review of safety data from several studies also found that rTMS is safe, even for younger people.

In summary, existing research supports the safety of TMS, with studies confirming it is well-tolerated and generally free from serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) for memory improvement because it offers a non-invasive and precise way to target brain regions involved in memory. Unlike standard treatments like medications or cognitive therapies, TMS uses magnetic fields to stimulate nerve cells, potentially leading to faster and more targeted improvements. Additionally, TMS may provide benefits with fewer side effects compared to pharmaceutical options, making it an appealing alternative for those seeking new avenues for cognitive enhancement.

What evidence suggests that this technique is effective for memory improvement?

Studies have shown that transcranial magnetic stimulation (TMS) can improve memory in both younger and older adults. Research indicates that using TMS in a personalized way to target specific brain areas linked to memory enhances thinking and daily functioning compared to sham treatments. This trial will compare the effects of TMS and sham stimulation on memory improvement. In Arm A, participants will receive TMS in the first week and sham stimulation in the second week. In Arm B, participants will receive sham stimulation in the first week and TMS in the second week. Additionally, TMS is considered a promising treatment for mild memory problems and early Alzheimer's disease. Specifically, another study found that repetitive TMS (rTMS) improved memory in people with mild memory issues compared to sham treatments. These findings suggest that TMS may boost memory by fine-tuning brain networks involved in memory. ^{6 7 8 9 10}

Who Is on the Research Team?

David E Warren, PhD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for adults over 19, either healthy or with mild memory issues (aMCI), who can follow instructions and sit still for tests. They must be right-handed and speak English natively. It's not for those with metal implants (except dental), major illnesses, substance abuse problems, seizures, other neurological disorders, or pregnant women.

Inclusion Criteria

Must be able to provide informed consent

I am a healthy adult with no psychiatric or neurological diseases, or I have been diagnosed with amnestic MCI.

Right-handed based on self-report (pre-screening) and evaluation with a standard test

Exclusion Criteria

I have high pressure inside my skull.

You have metal implants in your body that cannot be taken out, except for in your teeth.

You currently have a diagnosis of alcohol or drug addiction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial magnetic stimulation (TMS) and sham stimulation over two weeks

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in memory performance and brain connectivity

Approximately 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Targeted Transcranial Magnetic Stimulation

Trial Overview The study is testing if targeted brain stimulation using rTMS can improve memory in healthy young and older adults as well as those with aMCI by affecting brain network connectivity related to memory.

How Is the Trial Designed?

Group I: Arm B: Sham then Stimulation Experimental Treatment 1 Intervention

All procedures are identical in both arms with the exception of the order of stimulation administration. In Arm B, sham stimulation will be applied in the first week of participation, and transcranial magnetic stimulation (TMS) will be applied in the second week of participation.

Group II: Arm A: Stimulation then Sham Experimental Treatment 1 Intervention

All procedures are identical in both arms with the exception of the order of stimulation administration. In Arm A, transcranial magnetic stimulation (TMS) will be applied in the first week of participation, and sham stimulation will be applied in the second week of participation.

Targeted Transcranial Magnetic Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Migraine prevention
• Obsessive-compulsive disorder
• Smoking cessation
• Cognitive enhancement in certain neurological conditions

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Bipolar disorder
• Anxiety disorders
• Chronic pain management
• Cognitive rehabilitation

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Treatment-resistant depression
• Bipolar disorder
• Anxiety disorders
• Chronic pain management

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

Mild adverse effects (MAEs) from transcranial magnetic stimulation (TMS) occur in about 5% of sessions, with most symptoms like headache and nausea reported after the sessions, particularly during initial treatments.

The study found no significant links between participant characteristics (age and gender) or TMS parameters (frequency and intensity) and the occurrence of MAEs, suggesting that initial participant anxiety may play a role in these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Maizey, L., Allen, CP., Dervinis, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

Repetitive Transcranial Magnetic Stimulation (rTMS) targeting the left parietal cortex significantly improved memory performance in a patient with amnestic Mild Cognitive Impairment (aMCI).

The memory improvement was not only immediate but also sustained, remaining significant 24 weeks after the stimulation began, suggesting a lasting effect of rTMS on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation improves associative memory in an individual with amnestic mild cognitive impairment. Cotelli, M., Calabria, M., Manenti, R., et al.[2016]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Repetitive transcranial magnetic stimulation (rTMS) shows promise in enhancing memory function, particularly for age-related memory decline and conditions like Alzheimer's disease, which could improve independence and reduce healthcare costs.

Challenges such as varying rTMS protocols and outcome measures hinder the effectiveness and reproducibility of these interventions, but recent advances in cognitive neuroscience may help create more rigorous and clinically applicable studies in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulating Memory: Reviewing Interventions Using Repetitive Transcranial Magnetic Stimulation to Enhance or Restore Memory Abilities. Phipps, CJ., Murman, DL., Warren, DE.[2022]

In a study involving 22 patients (16 with amnesic mild cognitive impairment and 6 with Alzheimer's disease), repetitive transcranial magnetic stimulation (rTMS) targeting the left angular gyrus significantly improved episodic memory and cognitive assessment scores, particularly in aMCI patients.

The cognitive improvements were linked to changes in neuroplasticity within the thalamic system, suggesting that rTMS could be a promising strategy for enhancing cognitive function in the early stages of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Improvement via Left Angular Gyrus-Navigated Repetitive Transcranial Magnetic Stimulation Inducing the Neuroplasticity of Thalamic System in Amnesic Mild Cognitive Impairment Patients. Yang, Z., Sheng, X., Qin, R., et al.[2022]

In a study involving 429 pediatric patients undergoing transcranial magnetic stimulation (TMS) for motor and language mapping, most adverse events were benign, with seizures occurring in 5.8% of sessions but not conclusively linked to TMS.

TMS was safely performed in patients with cranial metal, and useful mapping results were achieved in nearly all cases, indicating that TMS is a safe option for functional mapping in pediatric patients with epilepsy or brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided TMS is safe in a predominately pediatric clinical population. Braden, AA., Weatherspoon, SE., Boardman, T., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly improves cognitive recovery in younger post-stroke patients, as shown by increased scores on the Montreal Cognitive Assessment and Rivermead Behavioral Memory Test across multiple studies involving 591 participants.

Both low-frequency (1 Hz) and high-frequency (10 Hz) rTMS treatments were found to be equally effective in enhancing attention and memory, suggesting flexibility in treatment options without added side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcranial magnetic stimulation on the recovery of attention and memory impairment following stroke: a systematic review and meta-analysis. Xu, WW., Liao, QH., Zhu, DW.[2023]

In a study involving 40 patients with mild cognitive impairment (MCI), 10 sessions of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex significantly improved memory performance compared to a sham treatment.

The improvement in memory was linked to changes in brain activity and connectivity, specifically increased activity in certain brain regions and altered functional connectivity, suggesting that rTMS may enhance memory by modulating neuronal networks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China: A Randomized Controlled Study. Wang, T., Guo, Z., Wu, H., et al.[2023]

Repetitive Transcranial Magnetic Stimulation (rTMS) shows promise in enhancing cognitive processes, particularly in patients with epilepsy, by helping to identify verbal memory lateralization and potentially improving memory performance.

Single-pulse TMS is effective for mapping motor output during learning, while rTMS can interfere with the retrieval of episodic and semantic memories, indicating its potential as a valuable tool for studying learning and memory in cognitive neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation can measure and modulate learning and memory. Grafman, J., Wassermann, E.[2019]

In a study involving 69 Alzheimer's disease patients, precision repetitive transcranial magnetic stimulation (rTMS) applied to the left parietal cortex significantly improved memory and cognitive function compared to sham treatment after 10 sessions over 2 weeks.

Patients receiving rTMS showed notable enhancements in various cognitive assessments, including the Mini-Mental State Examination and the Philadelphia Verbal Learning Test, indicating that targeting the left parietal cortex may offer a promising therapeutic approach for cognitive deficits in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision Repetitive Transcranial Magnetic Stimulation Over the Left Parietal Cortex Improves Memory in Alzheimer's Disease: A Randomized, Double-Blind, Sham-Controlled Study. Jia, Y., Xu, L., Yang, K., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

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Transcranial magnetic stimulation And, unlike electroconvulsive therapy (ECT), rTMS doesn't cause seizures or memory loss. It also doesn't require the use of anesthesia, which ...

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