TMS for Cognitive Impairment

Overseen By Hsin-Ju Lee, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Pregnancy, Seizure history, Metal implants, 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: 5

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how transcranial magnetic stimulation (TMS) can assist individuals with amnestic mild cognitive impairment (aMCI) by targeting specific brain areas to enhance cognitive function. TMS uses magnetic fields to stimulate brain nerve cells, and in this study, brain imaging and EEG (a test that measures brain waves) will guide its precise delivery. The trial includes two groups: healthy volunteers and those with aMCI who have noticed cognitive challenges but can still manage daily tasks independently. Participants should not have a history of seizures or major neurological issues and must be comfortable in an MRI machine. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new insights and treatments for cognitive impairment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What prior data suggests that this TMS approach is safe for cognitive impairment?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe and can enhance thinking skills in individuals with memory or cognitive problems. Studies have found that TMS, particularly when combined with EEG (a test that checks brain activity), is well-tolerated. Most participants experienced no major side effects. Some reported minor issues like headaches or scalp discomfort, but these typically resolved quickly. This evidence suggests the treatment is safe for both healthy volunteers and those with mild memory or cognitive issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the MRI Guided Closed-loop TMS-EEG technique because it represents a novel approach to tackling cognitive impairment. Unlike traditional treatments for cognitive decline, which often involve medications, this method uses transcranial magnetic stimulation (TMS) guided by MRI to target specific brain areas. By incorporating EEG feedback in a closed-loop system, it allows real-time adjustments, potentially enhancing the effectiveness and precision of the therapy. This innovative approach might lead to improvements in cognitive function with fewer side effects compared to conventional drug therapies.

What evidence suggests that MRI Guided Closed-loop TMS-EEG is effective for cognitive impairment?

Research has shown that transcranial magnetic stimulation (TMS) may improve thinking and memory in people with mild cognitive impairment. Studies have found TMS to be a safe, non-drug method for treating early Alzheimer's and similar conditions. This trial will use MRI Guided Closed-loop TMS-EEG, which stimulates specific brain areas to boost function. When combined with EEG, a tool that measures brain activity, TMS can be more accurately targeted, increasing its effectiveness. Early results suggest this method can enhance memory and thinking skills in those facing cognitive challenges. Overall, TMS is gaining attention as a promising treatment for cognitive impairment. ^{1 2 4 5 6}

Who Is on the Research Team?

Fa-Hsuan Lin, PhD

Principal Investigator

Sunnybrook Research Institute

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 20 to 65 with normal or corrected vision and no history of neurological issues. Participants must be able to consent and should not have a cardiac pacemaker, metal, or other implanted devices in their body.

Inclusion Criteria

You are in good health and have no prior history of neurological issues.

I am between 20 and 65 years old.

You are capable of providing admissible informed consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

MRI Session

Participants undergo MRI scans including structural and functional MRI, with training and preparation for EEG if applicable

1 day

1 visit (in-person)

TMS-MRI Session

Participants undergo TMS and MRI separately, with TMS protocol based on MRI scans, EEG signals, or motor responses

2 days

2 visits (in-person)

TMS-EEG-MRI Session

Participants undergo TMS and EEG together, followed by MRI, with protocol based on MRI scans, EEG signals, or motor responses

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MRI Guided Closed-loop TMS-EEG

Trial Overview The study tests an individualized brain stimulation method using TMS guided by MRI and EEG. It aims to modulate brain activity at multiple sites simultaneously, tailoring the placement of TMS coils based on fMRI data and timing pulses with EEG rhythms.

How Is the Trial Designed?

Group I: Experimental_Aim2: Amnestic Mild Cognitive Impairment Experimental Treatment 1 Intervention

All participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects.

Group II: Experimental_Aim1: Healthy Volunteers Experimental Treatment 1 Intervention

All participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects.

MRI Guided Closed-loop TMS-EEG is already approved in United States, European Union for the following indications:

Approved in United States as TMS-EEG for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Bipolar Depression

Approved in European Union as TMS-EEG for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

The study found that applying transcranial magnetic stimulation (TMS) concurrently with a somatosensory stimulus enhanced the P25 component of the somatosensory-evoked potential (SEP), indicating a significant interaction between sensory processing and TMS.

This enhancement was specifically observed in EEG recordings from the area of the brain directly under the TMS coil, suggesting that TMS can modulate sensory processing in the somatosensory cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EEG responses to combined somatosensory and transcranial magnetic stimulation. Schürmann, M., Nikouline, VV., Soljanlahti, S., et al.[2019]

Transcranial magnetic stimulation (TMS) is generally safe and does not cause persistent changes in cognitive function or EEG, although transient effects may occur during treatment.

While TMS does not typically induce seizures, there is a potential risk for individuals with heightened susceptibility, indicating that further research is needed to fully understand any unwanted effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects. Bridgers, SL.[2007]

Combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows researchers to non-invasively measure how the brain responds to stimulation, enhancing our understanding of brain function.

Using neuronavigation tools with TMS-EEG improves the accuracy of targeting specific brain areas and helps standardize measurements, which is crucial for developing reliable biomarkers for neurological and psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of neuronavigation in TMS-EEG studies: Current applications and future perspectives. Lioumis, P., Rosanova, M.[2022]

The integration of transcranial magnetic stimulation (TMS) with electroencephalographic (EEG) imaging allows researchers to gain real-time insights into how the brain reacts and connects, enhancing our understanding of brain function and behavior.

This TMS-EEG technique can reveal individual differences in brain responses and how these responses change during tasks, which could significantly advance both clinical applications and basic neuroscience research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining TMS and EEG offers new prospects in cognitive neuroscience. Miniussi, C., Thut, G.[2009]

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) is a promising technology for studying and influencing brain networks, with applications in both health and disease across various age groups and species.

To maximize the effectiveness of TMS-EEG, there is a need for standardized study protocols, and this article provides guidelines for designing and conducting TMS-EEG experiments to ensure reliable results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography. Farzan, F., Vernet, M., Shafi, MM., et al.[2018]

An optimized sham procedure was developed to effectively control for auditory and somatosensory stimulation during transcranial magnetic stimulation (TMS), allowing for reliable separation of transcranially evoked potentials (TEPs) from peripherally evoked potentials (PEPs) in EEG recordings.

In a study with 23 healthy participants, the optimized sham TMS condition successfully masked sensory inputs, revealing distinct EEG signal changes and increased beta band power only in the real TMS condition, indicating direct cortical activation in the primary motor cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recording brain responses to TMS of primary motor cortex by EEG - utility of an optimized sham procedure. Gordon, PC., Jovellar, DB., Song, Y., et al.[2022]

Transcranial magnetic stimulation (TMS) has a strong safety record, with seizures being an extremely rare adverse effect, particularly in patients receiving repetitive TMS (rTMS) under certain conditions.

The updated guidelines provide comprehensive safety recommendations for TMS applications, including risk assessments for new stimulation paradigms and precautions for use in patients with implanted devices or in neuroimaging settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Rossi, S., Hallett, M., Rossini, PM., et al.[2022]

Transcranial magnetic stimulation (TMS) is safe to use with implanted deep brain stimulation (DBS) devices at low to moderate intensities, as no movement or temperature increase was observed during stimulation at 0.2 Hz with 100% intensity for 1 hour.

However, caution is advised when using high-intensity TMS (over 50%) near looped DBS leads, as it can exceed the safety limit for charge density, potentially leading to electrical tissue injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. Shimojima, Y., Morita, H., Nishikawa, N., et al.[2010]

In a study involving 14 participants (5 with Alzheimer's disease, 5 with mild cognitive impairment, and 4 healthy controls), navigated transcranial magnetic stimulation (TMS) combined with EEG revealed significantly reduced neuronal responses in Alzheimer's patients, indicating impaired cortical reactivity.

The findings suggest that this method could serve as a novel tool for assessing functional cortical connectivity and the progression of dementia, as evidenced by decreased TMS-evoked responses in both Alzheimer's and mild cognitive impairment subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer's disease: a pilot study. Julkunen, P., Jauhiainen, AM., Westerén-Punnonen, S., et al.[2022]

The 10-20 system for EEG electrode placement can reliably target specific brain regions for transcranial magnetic stimulation (TMS), as demonstrated in a study with 21 subjects where targeted areas were accurately identified using neuronavigation.

While the 10-20 system is effective for broader applications, about 10% of the time it may reach adjacent but functionally distinct brain areas, suggesting that individual differences should be considered for more precise targeting, potentially using neuroimaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using the international 10-20 EEG system for positioning of transcranial magnetic stimulation. Herwig, U., Satrapi, P., Schönfeldt-Lecuona, C.[2022]

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) effectively distinguishes between healthy individuals and those with mild cognitive impairment (MCI) or Alzheimer's disease (AD), based on a reanalysis of data from 14 subjects (4 controls, 5 MCI, 5 AD).

The P30 amplitude response from TMS-EEG showed a strong correlation with cognitive decline, indicating its potential as a sensitive and specific biomarker for identifying cognitive impairment in early stages of dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining transcranial magnetic stimulation and electroencephalography may contribute to assess the severity of Alzheimer's disease. Julkunen, P., Jauhiainen, AM., Könönen, M., et al.[2021]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06050603

NCT06050603 | MRI Guided Closed-loop TMS-EEG The goal of this interventional study is to develop an individualized approach using transcranial magnetic stimulation (TMS) in a high-precision manner.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11306417/

Efficacy and Safety of Transcranial Magnetic Stimulation on ... The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213158225000890

Network-targeted transcranial magnetic stimulation (TMS) ... Transcranial magnetic stimulation (TMS) is a promising non-pharmacological intervention for treatment of mild cognitive impairment (MCI) and early Alzheimer's ...

4. withpower.com withpower.com/trial/phase-normal-physiology-8-2023-25fa4

TMS for Cognitive Impairment What data supports the effectiveness of the treatment MRI Guided Closed-loop TMS-EEG for cognitive impairment? Research suggests that combining transcranial ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11226590/

Exploring the potential of combining transcranial magnetic ... This review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7997266/

TMS–EEG Co-Registration in Patients with Mild Cognitive ... We performed here a systematic review of the studies employing TMS–EEG co-registration in patients with dementias.