Transcranial Magnetic Stimulation for Motor Skill Learning

Overseen By Manasi Wali

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must not be taking: Antidepressants, Antipsychotics, Antibiotics, others

Disqualifiers: Vision problems, Headaches, Heart disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different brain regions help people perceive limb position and hand movement. The study uses transcranial magnetic stimulation, a non-invasive brain stimulation method, to determine if it can enhance motor skill learning. Right-handed individuals without recent COVID symptoms and no major health issues, such as severe headaches or heart disease, may qualify.

As an unphased study, this trial offers participants a unique opportunity to contribute to groundbreaking research on brain function and motor skills.

Do I need to stop my current medications for the trial?

Yes, you must stop taking medications or drugs that affect cortical excitability and seizure risk, such as certain antidepressants, antipsychotics, and antibiotics, among others. The trial does not specify a washout period.

What prior data suggests that transcranial magnetic stimulation is safe for motor skill learning?

Research has shown that theta burst transcranial magnetic stimulation (TBS) is generally safe. Studies have tested TBS on over 1,000 people, including both healthy individuals and those with various health conditions. Most participants tolerated the treatment well, experiencing no serious issues.

No major problems have occurred when TBS targeted the cerebellum, the part of the brain that helps control movement. Additionally, studies with children found a specific type of TBS to be safe, with no significant discomfort or side effects.

This treatment is used in various research settings and is part of clinical practices for some conditions. While every treatment carries some risk, evidence indicates that TBS is mostly safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using theta burst transcranial magnetic stimulation (cTBS) for motor skill learning because it offers a novel way to enhance brain function. Unlike traditional methods like physical therapy that focus on repeated practice, cTBS uses magnetic fields to stimulate specific brain areas, potentially speeding up the learning process. Theta burst stimulation targets the brain's supramarginal gyrus and dorsolateral prefrontal cortex, regions involved in coordinating movement and cognitive control. This approach could offer a quicker, more efficient boost to motor learning compared to standard practices.

What evidence suggests that this trial's treatments could be effective for motor skill learning?

This trial will compare the effects of theta burst transcranial magnetic stimulation (TBS) applied over different brain regions with a sham control. Research has shown that TBS can greatly improve motor skills by boosting brain activity. One study found that TBS increased brain activity by about 35% for up to an hour. TBS also enhances learning and memory, making it a promising tool for helping people regain motor skills. While most research focuses on recovery after a stroke, these findings suggest that TBS might also improve motor skills in other situations. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for right-handed individuals aged 18-45, free of COVID symptoms, without metal implants (except titanium), dreadlocks/weaves/extensions, hand/arm injuries not fully recovered, magnetic/metallic/mechanical implants, claustrophobia issues, IUDs with unknown MR compatibility. Pregnant women or those who might be pregnant are excluded. Participants must avoid excessive alcohol/drugs/caffeine and lack sleep before testing.

Inclusion Criteria

Only right-handed individuals will be tested

I haven't had any Covid symptoms in the last week.

Exclusion Criteria

I do not have any major visual, hearing, balance issues, or a history of severe neurological conditions.

I have vision problems not fixed by glasses or contacts.

I do not have severe headaches, glaucoma, heart or lung disease, high blood pressure, psychiatric conditions, or learning/attention issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive theta burst transcranial magnetic stimulation (cTBS) over specific brain regions and perform proprioceptive and motor skill learning tasks

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any immediate effects post-treatment

1 day

What Are the Treatments Tested in This Trial?

Interventions

• Sham theta burst transcranial magnetic stimulation
• Theta burst transcranial magnetic stimulation

Trial Overview The study tests how brain regions contribute to proprioception and motor skill learning using Theta burst transcranial magnetic stimulation (TMS) versus a sham procedure. It aims to improve rehabilitation methods for patients with movement deficits by understanding the frontal and parietal brain areas' roles.

How Is the Trial Designed?

Group I: Supramarginal gyrus (SMG) Experimental Treatment 1 Intervention

Theta burst transcranial magnetic stimulation (cTBS) will be applied over the supramarginal gyrus (SMG).

Group II: Dorsolateral prefrontal cortex (DLPFC) Experimental Treatment 1 Intervention

Theta burst transcranial magnetic stimulation (cTBS) will be applied over dorsolateral prefrontal cortex (DLPFC).

Group III: Sham control group Placebo Group 2 Interventions

Sham theta burst transcranial magnetic stimulation (cTBS) will be applied over the vertex.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Intermediate theta-burst stimulation (imTBS) serves as a promising sham control in Transcranial Magnetic Stimulation (TMS) trials, as it uses real TMS pulses to mimic sensory effects without causing physiological aftereffects.

This review highlights the importance of improving sham protocols in TMS research to ensure more accurate comparisons between treatment and control groups, potentially enhancing the reliability of behavioral outcome assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of intermediate theta burst stimulation as sham control in therapeutic transcranial magnetic stimulation studies. Bagali, K., Sreeraj, VS., Mehta, UM., et al.[2023]

In a study involving 12 subacute stroke patients, prolonged transcranial magnetic stimulation (iTBS1200) was found to be safe and well-tolerated, with no significant adverse effects reported.

Patients receiving iTBS1200 showed measurable improvements in stroke severity and upper extremity function shortly after treatment and at 60 days post-stroke, suggesting potential benefits that warrant further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: a pilot study. Hsu, YF., Huang, YZ., Lin, YY., et al.[2022]

Prolonged motor practice over three weeks led to significant improvements in motor skills for the non-dominant arm, with similar benefits observed in the dominant arm, indicating enhanced overall sensorimotor abilities.

Inhibiting motor-related brain regions with continuous theta burst stimulation (cTBS) after extensive training did not harm motor performance; in fact, cTBS applied to the primary motor cortex (M1) even improved performance in certain tasks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged motor skill learning--a combined behavioural training and θ burst TMS study. Platz, T., Roschka, S., Doppl, K., et al.[2013]

Repeated applications of Theta Burst stimulation (TBS) in rats showed complex effects on neuronal activity markers, with some markers increasing while others decreased, indicating that the response to TBS is not simply accumulative.

Specifically, while the expression of the vesicular glutamate transporter (VGLUT1) increased with stimulation, markers for inhibitory activity like GAD67 and calcium-binding proteins decreased, suggesting a nuanced interaction between excitatory and inhibitory neuronal responses to repeated TBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. Volz, LJ., Benali, A., Mix, A., et al.[2016]

Theta burst stimulation (TBS) protocols, including continuous (cTBS) and intermittent (iTBS), appear to be safe for healthy individuals, with no seizures or serious side effects reported during the study involving 24 participants.

The most notable side effect was the occurrence of vagal reactions, and while some changes in brain activity were observed, there was no significant impact on mood or cognitive performance, indicating that further research is needed to fully understand the effects of TBS on the prefrontal cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta burst stimulation of the prefrontal cortex: safety and impact on cognition, mood, and resting electroencephalogram. Grossheinrich, N., Rau, A., Pogarell, O., et al.[2009]

Intermittent theta burst stimulation (iTBS) applied after motor learning can actually reduce motor performance and corticospinal excitability (CSE) in healthy participants, suggesting it may interfere with previously learned skills.

In a study with 24 participants who practiced a motor task, those who received iTBS after training showed a negative correlation between changes in CSE and performance, indicating that iTBS may reverse the benefits of motor learning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversed Effects of Intermittent Theta Burst Stimulation following Motor Training That Vary as a Function of Training-Induced Changes in Corticospinal Excitability. Stöckel, T., Summers, JJ., Hinder, MR.[2018]

In a study involving 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

In a study involving 30 healthy participants, inhibitory continuous theta burst stimulation (cTBS) decreased motor cortex excitability and slowed motor learning, while excitatory intermittent theta burst stimulation (iTBS) increased excitability but did not enhance learning performance.

The findings suggest that the effects of TBS on motor learning are more related to changes in motor cortex plasticity rather than just the level of activation, which could inform future neurorehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Jelić, MB., Milanović, SD., Filipović, SR.[2018]

Intermittent theta-burst stimulation (iTBS) applied to the primary motor cortex increased cortical excitability but did not significantly enhance practice-related improvements in motor performance during a finger abduction task in 17 healthy subjects.

Further investigation with an additional group of 5 subjects showed that neither real nor sham iTBS affected motor performance or retention after longer practice, suggesting that iTBS alone may not be sufficient to influence early motor learning, which likely involves a broader network in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta-burst stimulation on practice-related changes in fast finger movements in healthy subjects. Agostino, R., Iezzi, E., Dinapoli, L., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11605871/

The effectiveness of theta burst stimulation for motor recovery ... This paper provides a comprehensive overview and assessment of the current impact of TBS on motor rehabilitation following stroke

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X15008967

Efficacy and Time Course of Theta Burst Stimulation in ... ITBS applied for 190 s significantly increases cortical excitability up to 60 min with a mean maximum potentiation of 35.54 ± 3.32%.

3. dl.acm.org dl.acm.org/doi/10.1145/3707127.3707158

The Intermittent Theta-Burst Stimulation Induces a Lasting ... Moreover, iTBS exhibited positive effects on sequence retention and overall learning ability. These findings suggest that iTBS can be considered ...

4. nature.com nature.com/articles/s41598-025-11540-7

Effects of ball combination training program ... This study aims to investigate the effects of a 12-week ball combination training program (BCTP) combined with continuous theta burst stimulation (cTBS) on MD ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3260517/

Safety of Theta Burst Transcranial Magnetic Stimulation Of the 1001 subjects 776 were healthy control participants while 225 were clinical patients with a variety of diagnoses including autism spectrum disorders (n= ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291820302794

Safety Considerations for Cerebellar Theta Burst Stimulation No serious adverse events have been reported for cerebellar TBS. There is no substantial evidence of a tolerable maximal-efficacy stimulation dose in humans.

8. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.044892

Intermittent Theta-Burst Stimulation for Stroke: Primary ... This study aimed to compare the efficacy and safety of intermittent theta-burst stimulation (iTBS) to the cerebellum or M1 on balance and motor ...

9. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2015.00091/full

Effect of 30 Hz theta burst transcranial magnetic stimulation ... iTBS300 (stimulation duration of 92 s at 70% RMT) delivered over M1 in typically developed children was well-tolerated and produced on average significant ...

10. neuromodulationjournal.org neuromodulationjournal.org/article/S1094-7159(21)06424-2/pdf

A Systematic Review of the Safety and Tolerability of Theta ... Objectives: Theta burst stimulation (TBS) is often used in clinical practice and research protocols for adults with neuropsychiatric disorders.