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

Trial Summary

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 data supports the effectiveness of the treatment MRI Guided Closed-loop TMS-EEG for cognitive impairment?

Research suggests that combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) can reveal changes in brain activity related to cognitive impairment, such as in Alzheimer's disease and mild cognitive impairment. This method has shown potential in identifying differences in brain function between healthy individuals and those with cognitive decline, indicating it may be useful in assessing and monitoring these conditions. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) generally safe for humans?

TMS is generally considered safe for humans, with serious effects like seizures being extremely rare and often linked to exceeding guidelines or certain medications. Mild effects such as headaches and nausea can occur, but extensive use suggests no lasting impact on brain function. ^{6 7 8 9 10}

How is the TMS-EEG treatment for cognitive impairment different from other treatments?

The TMS-EEG treatment is unique because it combines brain stimulation with real-time brain activity monitoring, allowing for precise targeting and adjustment based on individual brain responses. This approach provides insights into brain connectivity and function, which can be tailored to each patient's needs, unlike traditional treatments that may not offer such personalized feedback. ^{1 4 11 12 13}

What is the purpose of this trial?

The goal of this interventional study is to develop an individualized approach using transcranial magnetic stimulation (TMS) in a high-precision manner. This approach will use TMS to modulate brain activity at multiple locations simultaneously. Functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) will record the responses and guide the stimulation. Specifically, the placement and orientation of TMS coils will be tailored to stimulate the targeted functional brain areas informed by fMRI. To maximize the interventional effect, stimulation pulses will be delivered based on EEG oscillations.

Research Team

Fa-Hsuan Lin, PhD

Principal Investigator

Sunnybrook Research Institute

Eligibility Criteria

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

I am between 20 and 65 years old.

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

You are capable of providing admissible informed consent.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

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

Combining TMS and EEG offers new prospects in cognitive neuroscience. [2009]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer's disease: a pilot study. [2022]

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

Using the international 10-20 EEG system for positioning of transcranial magnetic stimulation. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The role of neuronavigation in TMS-EEG studies: Current applications and future perspectives. [2022]

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

Combining transcranial magnetic stimulation and electroencephalography may contribute to assess the severity of Alzheimer's disease. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. [2010]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography. [2018]

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

Recording brain responses to TMS of primary motor cortex by EEG - utility of an optimized sham procedure. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

EEG responses to combined somatosensory and transcranial magnetic stimulation. [2019]