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: Unknown

87 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to understand how the different regions of the brain affect our sense of limbs in space (proprioception) and in turn our hand movements (motor skill learning). This information might help us one day to generate better rehabilitation protocols to help patients with movement deficits.

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 data supports the idea that Transcranial Magnetic Stimulation for Motor Skill Learning is an effective treatment?

The available research shows that Transcranial Magnetic Stimulation (TMS) can be effective for motor skill learning. For example, one study found that using TMS in the form of intermittent theta burst stimulation (iTBS) helped improve manual dexterity and motor function in patients with multiple sclerosis. Another study indicated that iTBS could enhance motor learning when applied early in the learning process. These findings suggest that TMS can positively impact motor skills, supporting its effectiveness as a treatment. ^{1 2 3 4 5}

What safety data is available for Transcranial Magnetic Stimulation (TMS) used in motor skill learning?

The safety of theta burst stimulation (TBS), including its variants like intermittent TBS (iTBS) and continuous TBS (cTBS), has been explored in several studies. One study reviewed the use of intermediate TBS (imTBS) as a sham control, indicating it mimics sensory effects without physiological aftereffects, suggesting a safe sham alternative. Another study focused on the safety of TBS on cognition, mood, and EEG in healthy subjects, indicating a need for further exploration of side effects. Overall, while TBS is considered promising, more research is needed to fully understand its safety profile. ^{1 2 4 6 7}

Is Transcranial Magnetic Stimulation a promising treatment for motor skill learning?

Transcranial Magnetic Stimulation (TMS) shows potential as a treatment for motor skill learning because it can change brain activity related to movement. Some studies suggest it might help improve motor skills by affecting brain areas involved in learning new movements. However, the results are mixed, and more research is needed to understand its full effects. ^{1 3 4 8 9}

Eligibility Criteria

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.

I am between 18 and 45 years old and right-handed.

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.

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Prolonged motor skill learning--a combined behavioural training and θ burst TMS study. [2013]

2. Estonia 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. [2020]

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

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. [2016]

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

Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. [2018]

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

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: a pilot study. [2022]

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

Feasibility of intermediate theta burst stimulation as sham control in therapeutic transcranial magnetic stimulation studies. [2023]

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

Theta burst stimulation of the prefrontal cortex: safety and impact on cognition, mood, and resting electroencephalogram. [2009]

8. France pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta-burst stimulation on practice-related changes in fast finger movements in healthy subjects. [2019]

9. United States 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. [2018]