rTMS for Navigation Ability in Healthy Subjects

Overseen By Daniel Dilks, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Must not be taking: Bupropion, Benzodiazepines, others

Disqualifiers: Epilepsy, Brain injury, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how people navigate familiar spaces, such as walking around a bedroom effortlessly. Researchers use repetitive transcranial magnetic stimulation (rTMS) to temporarily affect certain brain areas and observe their role in navigation. Participants view pictures of rooms and perform simple tasks. The trial consists of two parts: one group completes computer-based tasks, while another engages in behavioral tasks, both while receiving rTMS. Ideal participants have normal vision and no history of seizures or brain injuries. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in understanding brain function and navigation.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications that increase the risk of seizures or reduce the effects of rTMS, like bupropion, varenicline, chlorpromazine, theophylline, and benzodiazepines.

What prior data suggests that this technique is safe for healthy subjects?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated. This non-invasive method treats various brain-related conditions. Some people might experience side effects, such as headaches or discomfort at the treatment site, but these effects are usually mild and temporary. No evidence of long-term negative side effects suggests rTMS is safe for short-term use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using repetitive transcranial magnetic stimulation (rTMS) for enhancing navigation skills because it taps into the brain's ability to process spatial information differently than traditional methods. Unlike current navigation aids or cognitive training which often rely on visual cues or memorization, rTMS directly stimulates specific brain areas involved in navigation, potentially leading to faster improvements. This non-invasive technique could offer a new way to boost cognitive functions without the need for medications or lengthy training programs.

What evidence suggests that rTMS is effective for visually-guided navigation?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can temporarily alter the function of certain brain areas. This method has been used to study regions involved in tasks like speaking and moving. Some studies suggest that rTMS may help treat conditions such as Alzheimer's disease and depression by targeting specific brain regions. In this trial, participants will receive rTMS during either computer-based or behavioral tasks to examine its effects on visually-guided navigation. The goal is to use rTMS to better understand how the brain aids in spatial navigation by observing changes in task performance. While rTMS holds promise for treating some conditions, this study focuses on understanding brain functions in healthy individuals. ^{6 7 8 9 10}

Who Is on the Research Team?

Daniel Dilks, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for healthy adults with normal or corrected-to-normal vision. It's not suitable for those with metal in their body, a personal or family history of seizures, known brain injury, on specific medications (like bupropion or benzodiazepines), claustrophobic individuals, those unable to consent, pregnant women, and prisoners.

Inclusion Criteria

You have normal vision or can correct your vision to normal with glasses or contacts.

Exclusion Criteria

You have metal in your body.

You or a close family member has a history of seizures.

You have a known brain injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

fMRI Scanning

Participants undergo an fMRI scan to identify the occipital place area (OPA) location

1 day

1 visit (in-person)

rTMS Intervention

Participants receive rTMS while performing computer-based and behavioral-based tasks to examine the causal involvement of OPA in visually-guided navigation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any immediate effects post-rTMS intervention

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The study uses repetitive Transcranial Magnetic Stimulation (rTMS) to understand how the brain helps people navigate spaces like rooms without bumping into things. Participants will have certain brain areas temporarily disrupted while they perform computer tasks or simple actions based on visual cues.

How Is the Trial Designed?

Group I: Repetitive Transcranial Magnetic Stimulation (rTMS) During Computer-based Task Experimental Treatment 2 Interventions

Participants receiving rTMS while they perform computer-based tests to examine the causal involvement of OPA in visually-guided navigation. The study visit lasts approximately 90 minutes.

Group II: Repetitive Transcranial Magnetic Stimulation (rTMS) During Behavioral-based Task Experimental Treatment 2 Interventions

Participants receiving rTMS while they perform behavioral-based tests to examine the causal involvement of OPA in visually-guided navigation. The study visit lasts approximately 90 minutes.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Published Research Related to This Trial

Low-frequency repetitive transcranial magnetic stimulation (rTMS) significantly increased current perception thresholds, indicating a global anesthetic effect on sensory functions in healthy subjects.

rTMS also decreased the amplitude of somatosensory evoked potentials, suggesting reduced excitability in the primary sensory cortex, which may have implications for treating chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in sensory functions after low-frequency repetitive transcranial magnetic stimulation over the motor cortex. Kodama, M., Aono, K., Masakado, Y.[2011]

Neuronavigated low-frequency rTMS significantly enhances motor-evoked potentials and improves motor behavior, such as reaction time and grip strength, compared to non-navigated rTMS in healthy subjects.

The study involved 10 participants and demonstrated that navigated rTMS leads to more pronounced effects on the contralateral hemisphere, suggesting its potential for better therapeutic outcomes in stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuronavigation increases the physiologic and behavioral effects of low-frequency rTMS of primary motor cortex in healthy subjects. Bashir, S., Edwards, D., Pascual-Leone, A.[2022]

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]

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]

In a study involving nine healthy males, 1-Hz rTMS over the left primary motor cortex significantly increased reaction time and movement time, indicating a slowing effect on motor performance.

Conversely, 10-Hz rTMS led to a decrease in reaction time and movement time, suggesting that higher frequency stimulation may enhance the initiation and execution of voluntary movements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of rTMS over the left primary motor cortex on initiation and performance of a simple movement executed with the contralateral arm in healthy volunteers. Di Lorenzo, C., Tavernese, E., Lepre, C., et al.[2021]

In a study involving 14 healthy subjects, repetitive transcranial magnetic stimulation (rTMS) at 20 Hz on the left prefrontal cortex significantly improved cognitive processing, as shown by decreased P3 latencies and faster reaction times.

The study demonstrated that rTMS has a measurable effect on cognitive processing, while single TMS at 1 Hz did not show any significant impact, highlighting the efficacy of rTMS over traditional stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of transcranial magnetic stimulation on cognitive processing: an event-related potential study. Evers, S., Böckermann, I., Nyhuis, PW.[2019]

Low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the primary motor cortex (M1) significantly decreased motor excitability in targeted hand muscles, as evidenced by increased resting motor thresholds and suppressed motor evoked potentials (MEPs) for up to 30 minutes after stimulation.

Despite the decrease in motor excitability, basic motor behaviors, such as peak force and acceleration during thumb and finger movements, were not affected, suggesting that low-frequency rTMS may be safe for therapeutic applications without impairing motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior. Muellbacher, W., Ziemann, U., Boroojerdi, B., 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]

Transcranial magnetic stimulation (TMS) is a non-invasive brain imaging technique that can causally link specific cortical areas to physiological responses, making it more precise than other imaging methods.

Navigated TMS has shown clinical effectiveness in mapping motor areas, assessing recovery after stroke, and treating conditions like depression, but further development of targeting and dosing protocols is needed for improved accuracy and reproducibility in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navigated transcranial magnetic stimulation. Ruohonen, J., Karhu, J.[2016]

In a study involving five healthy participants, it was found that adjusting the coil angulation to 90° from the standard anterior-posterior position significantly increased naming errors in Broca's area, suggesting that the traditional coil positioning may not be optimal for language mapping.

The study identified that using a stimulation frequency of 20 Hz and an intensity of 120% of the resting motor threshold (RMT) provided the best results for eliciting language impairments, highlighting the importance of customizing stimulation parameters for effective rTMS mapping.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of repetitive navigated transcranial magnetic stimulation coil positioning and stimulation parameters on human language function. Sollmann, N., Ille, S., Obermueller, T., et al.[2018]

In a study involving 6 healthy subjects, repeated short trains of rapid-rate transcranial magnetic stimulation (rrTMS) at 20 Hz and slightly above motor threshold were found to be safe, with no adverse effects on neurological, cognitive, or motor functions.

The study observed transient increases in motor evoked potentials (MEPs) in some subjects, suggesting that rrTMS may enhance cortical excitability, indicating its potential utility in studying cognitive and motor functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid rate transcranial magnetic stimulation--a safety study. Jahanshahi, M., Ridding, MC., Limousin, P., et al.[2019]

Navigated transcranial magnetic stimulation (nTMS) demonstrated a high sensitivity of 90.2% for identifying language areas in patients with left-sided cerebral lesions, indicating it is effective for presurgical mapping.

While nTMS showed excellent sensitivity, particularly in mapping Broca's area (100% sensitivity), its low specificity (23.8% overall) suggests that further refinement is needed to improve accuracy in identifying posterior language areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of language mapping by preoperative navigated transcranial magnetic stimulation and direct cortical stimulation during awake surgery. Picht, T., Krieg, SM., Sollmann, N., et al.[2022]

Citations

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Evaluating the treatment outcomes of repetitive transcranial ... The repetitive transcranial magnetic stimulation (rTMS) shows great potential in the treatment of Alzheimer's disease (AD).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4942051/

Neuronavigation-guided Repetitive Transcranial Magnetic ... This study protocol demonstrates a method to induce virtual aphasia in healthy subjects by neuronavigational rTMS targeting Broca's area, using individual ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04707378

Navigated Repetitive Transcranial Magnetic Stimulation for ... In this study, we applied repetitive transcranial magnetic stimulation with neuronavigation to treat patients with Parkinson's disease and depression, and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X21000966

Navigated repetitive transcranial magnetic stimulation ... The present study examines the effect of postoperative nrTMS therapy of the unaffected hemisphere in glioma patients suffering from acute surgery-related ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724017804

A preliminary comparison of the clinical efficacy ... To compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated ...

6. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Generally, rTMS is considered safe and well-tolerated. However, it can cause some side effects. Common side effects. Side effects are generally ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11126186/

Side effects of repetitive transcranial magnetic stimulation The side effects of repetitive transcranial magnetic stimulation are largely unexplored and the limits of safe exposure have not been determined.

8. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(23)01862-4/fulltext

Deep TMS: A comprehensive summary of adverse events ... The most common events associated with active TMS were headache (35.43%), treatment site discomfort (29.92%), muscle spasm (5.91%), jaw pain ( ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568715/

Repetitive Transcranial Magnetic Stimulation - StatPearls - NCBI Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive treatment technique used to treat various psychiatric and neurological disorders.

10. cognitivefxusa.com cognitivefxusa.com/blog/side-effects-of-tms-benefits-vs-risks

Side Effects of TMS: Do the Benefits Outweigh the Risks? No long-term negative side effects have been reported and TMS is considered a safe procedure. This applies to the various types of TMS, ranging ...