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

11 Participants Needed

Trial Summary

What is the purpose of this trial?

This study investigates the neural mechanisms causally involved in how people navigate through their immediately visible environment (e.g., walking around one's bedroom flawlessly and effortlessly, not bumping into the walls or furniture). To investigate whether particular neural mechanisms are causally involved in "visually-guided navigation", repetitive transcranial magnetic stimulation (rTMS) is used to temporarily disrupt the functioning of particular brain regions in healthy adults while they are shown simple visual stimuli of places (e.g., bedrooms, kitchens, and living rooms) and asked to perform simple computer tasks or to complete simple behavioral tasks.

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 data supports the idea that rTMS for Navigation Ability in Healthy Subjects is an effective treatment?

The available research shows that navigated rTMS can improve reaction time and pinch force in healthy subjects. In one study, navigated rTMS led to significant improvements in these areas, while non-navigated rTMS did not show significant changes. This suggests that navigated rTMS is more effective in enhancing certain motor behaviors. ^{1 2 3 4 5}

What safety data exists for rTMS treatment?

Safety data for repetitive transcranial magnetic stimulation (rTMS) has been extensively reviewed and updated over the years. Initial safety guidelines were published in 1996, with updates in 2008 and 2021, focusing on conventional rTMS protocols. Studies have shown that rTMS is generally safe when applied within established guidelines, with potential adverse events being rare. Research has demonstrated that neuronavigated rTMS can enhance physiological and behavioral effects without significant adverse outcomes. Rapid-rate TMS studies also indicate safety in healthy subjects, with no adverse effects observed when following published guidelines. Overall, rTMS is considered a safe technique for both research and clinical applications when proper precautions are taken. ^{1 6 7 8 9}

Is the treatment rTMS promising for improving navigation ability in healthy people?

Yes, rTMS is promising because it can improve motor skills, reaction times, and cognitive processing, which are important for navigation. ^{1 4 10 11 12}

Research Team

Daniel Dilks, PhD

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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) 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 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]

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) 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]

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]

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]

References

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

Neuronavigation increases the physiologic and behavioral effects of low-frequency rTMS of primary motor cortex in healthy subjects. [2022]

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

The impact of repetitive navigated transcranial magnetic stimulation coil positioning and stimulation parameters on human language function. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

Changes in sensory functions after low-frequency repetitive transcranial magnetic stimulation over the motor cortex. [2011]

4. France pubmed.ncbi.nlm.nih.gov

Navigated transcranial magnetic stimulation. [2016]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior. [2022]

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Rapid rate transcranial magnetic stimulation--a safety study. [2019]

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

Image-guided TMS is safe in a predominately pediatric clinical population. [2022]

9. Ireland 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. [2022]

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

A comparison of language mapping by preoperative navigated transcranial magnetic stimulation and direct cortical stimulation during awake surgery. [2022]

11. Germany 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. [2021]

12. England pubmed.ncbi.nlm.nih.gov

The impact of transcranial magnetic stimulation on cognitive processing: an event-related potential study. [2019]