Transcranial Magnetic Stimulation for Sensory Learning Studies

Overseen By Hannah J Block, PhD

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)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the brain maintains accurate hand movements, potentially enhancing rehabilitation for individuals with brain injuries. It uses transcranial magnetic stimulation (TMS), a technique that employs magnetic fields to stimulate different brain areas. Participants will receive either real or sham (fake) stimulation over specific brain regions. The trial seeks right-handed individuals without certain health issues who are fully vaccinated against Covid or have a negative test. It is suitable for those without current vision problems, severe headaches, or past serious injuries affecting their hands or arms. As an unphased trial, this study allows participants to contribute to groundbreaking research that could improve rehabilitation methods for brain injuries.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that affect brain activity, such as antidepressants, antipsychotics, and some antibiotics, as they can influence the study results. It's best to discuss your specific medications with the study team to see if they are on the exclusion list.

What prior data suggests that theta burst transcranial magnetic stimulation is safe for sensorimotor learning studies?

Research has shown that theta burst transcranial magnetic stimulation (TBS) is generally well-tolerated. Studies have found TBS to be as safe as other similar brain stimulation methods, with side effects comparable to those of other approved treatments. Notably, no serious side effects have been reported specifically for cerebellar TBS, one of the areas targeted in the trial.

While there is a theoretical risk of seizures, this risk does not exceed that of other brain stimulation techniques. Overall, TBS has been used safely in studies without major issues, offering some confidence in its safety for participants considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using transcranial magnetic stimulation (TMS) for sensory learning because it offers a fresh, non-invasive approach to brain stimulation. Unlike traditional treatments that might involve medication or surgery, TMS uses magnetic fields to stimulate specific brain areas quickly and painlessly. This method can target regions like the somatosensory or motor cortex directly, potentially enhancing sensory processing and learning capabilities. By offering a precise way to influence brain activity, TMS could lead to faster and more targeted improvements in sensory functions without the side effects commonly associated with drugs.

What evidence suggests that theta burst transcranial magnetic stimulation is effective for sensorimotor learning?

This trial will explore the effects of theta burst transcranial magnetic stimulation (TBS) on various brain regions. Research has shown that TBS can improve movement, particularly in individuals who have experienced a stroke. The trial will apply TBS to different brain areas, including the primary motor cortex, primary somatosensory cortex, anterior superior parietal lobule, ventral premotor cortex, and cerebellar cortex, to assess its effects on movement, sensation, memory, thinking skills, coordination, and mood. Sham TBS will be applied over the vertex as a comparator. Overall, theta burst TMS is a promising technique with potential benefits for different brain functions. ^{6 7 8 9 10}

Who Is on the Research Team?

Hannah J Block, PhD

Principal Investigator

Indiana University, Bloomington

Are You a Good Fit for This Trial?

This trial is for right-handed individuals aged 18-45, free of COVID symptoms and either fully vaccinated or with a recent negative test. Excluded are those with visual/hearing impairments, metal head implants (except titanium), severe hand/arm injuries, drug/alcohol use before testing, sleep deprivation, or certain medical conditions.

Inclusion Criteria

Subjects must be fully vaccinated (2+ weeks past their final vaccine dose) or have a negative Covid test within 4 days of testing

I have not had any COVID-19 symptoms in the past week.

Exclusion Criteria

I have severe headaches, glaucoma, heart, lung, high blood pressure, mental health issues, or learning/attention problems.

I have had symptoms like those of Covid in the last week and am not fully vaccinated or haven't tested negative in the past 4 days.

Subjects who have drunk more than 3 units of alcohol or taken other recreational drugs in the 24-hour period prior to testing; have had more than 3 cups of coffee in the last hour; are sleep deprived (<4 hours sleep the previous night); or have participated in another brain stimulation experiment the same day

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo theta burst transcranial magnetic stimulation (cTBS) over various brain regions and perform reaching tasks

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in motor cortex excitability and other sensory-motor outcomes

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Theta burst transcranial magnetic stimulation

Trial Overview The study tests how brain stimulation using Theta burst transcranial magnetic stimulation affects sensorimotor learning. It aims to improve understanding of brain regions involved in maintaining accurate hand movements which could enhance rehabilitation for patients with brain lesions.

How Is the Trial Designed?

Group I: Ventral premotor cortex--Exp 2 Experimental Treatment 1 Intervention

Theta burst transcranial magnetic stimulation (cTBS) will be applied over Ventral premotor cortex.

Group II: Somatosensory cortex--Exp 1 Experimental Treatment 1 Intervention

Theta burst transcranial magnetic stimulation (cTBS) will be applied over primary somatosensory cortex.

Group III: Primary motor cortex--Exp 1 Experimental Treatment 1 Intervention

Theta burst transcranial magnetic stimulation (cTBS) will be applied over primary motor cortex.

Group IV: Cerebellar cortex--Exp 2 Experimental Treatment 1 Intervention

Theta burst transcranial magnetic stimulation (cTBS) will be applied over cerebellar cortex.

Group V: Anterior superior parietal lobule--Exp 2 Experimental Treatment 1 Intervention

Theta burst transcranial magnetic stimulation (cTBS) will be applied over Anterior superior parietal lobule.

Group VI: Vertex sham--Exp 1 Placebo Group 1 Intervention

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

Group VII: Vertex sham--Exp 2 Placebo Group 1 Intervention

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

Intermittent theta-burst stimulation (iTBS) significantly enhances late sensory response components in the rat barrel cortex, indicating its potential to modulate cortical excitability and improve sensory processing, especially with repeated applications.

Continuous theta-burst stimulation (cTBS) initially reduces early sensory responses but can mimic iTBS effects after multiple applications, suggesting that both forms of stimulation can influence cortical activity, albeit through different mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex. Thimm, A., Funke, K.[2018]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

The study found that continuous theta-burst stimulation (cTBS) can effectively reduce cortical excitability, but its effects show limited reproducibility across sessions, indicating variability in its impact.

Among the neurophysiological markers assessed, the modulation of corticospinal excitability measured 5 minutes after cTBS was the most consistent, suggesting it could be a reliable measure for future research on cTBS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants. Vernet, M., Bashir, S., Yoo, WK., et al.[2022]

Theta-burst stimulation (TBS) was found to be safe for children, with no serious adverse events reported among 40 participants aged under 18, including those with Tourette syndrome and typically developing children.

Only 11.6% of participants experienced mild, self-limited side effects, such as finger twitching and headaches, indicating that TBS is well tolerated in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. Wu, SW., Shahana, N., Huddleston, DA., et al.[2012]

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]

A modified theta burst stimulation protocol adapted for transcranial magnetic stimulation (TMS) can induce long-lasting effects on motor cortex function and behavior for up to an hour.

This research suggests potential clinical applications of repetitive TMS (rTMS) in treating various neurological and psychiatric conditions, including depression, epilepsy, and Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward establishing a therapeutic window for rTMS by theta burst stimulation. Paulus, W.[2005]

Intermittent theta burst stimulation (iTBS) enhances learning in rats by reducing the expression of inhibitory proteins in the cortex, while continuous theta burst stimulation (cTBS) does not have this effect.

The improved learning associated with iTBS is linked to a balance between reduced inhibition from fast-spiking interneurons and increased activity in neurons involved in the learning task, suggesting a complex interaction that optimizes learning processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous and intermittent transcranial magnetic theta burst stimulation modify tactile learning performance and cortical protein expression in the rat differently. Mix, A., Benali, A., Eysel, UT., et al.[2010]

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]

Transcranial magnetic intermittent theta burst stimulation (iTBS) over the sensory cortex (S1) significantly enhanced somatosensory evoked potentials (SEPs) in healthy subjects, indicating its potential to facilitate sensory processing.

The effectiveness of iTBS was dependent on the position and direction of the stimulation coil, with no significant changes observed when applied over the motor cortex (M1), suggesting that iTBS can selectively modulate sensory pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of somatosensory evoked potentials using transcranial magnetic intermittent theta burst stimulation. Katayama, T., Rothwell, JC.[2008]

Intermittent theta burst stimulation (iTBS) applied to the primary motor cortex (M1) significantly reduced cortical inhibition, as evidenced by decreased N100 amplitude in TMS-evoked potentials, indicating enhanced cortical excitability.

The study involved 18 young adults and demonstrated that iTBS specifically affects the M1, leading to changes in motor performance and cortical network dynamics, suggesting potential therapeutic applications for neurological and psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation to the Primary Motor Cortex Reduces Cortical Inhibition: A TMS-EEG Study. Bai, Z., Zhang, J., Fong, KNK.[2021]

Theta burst transcranial magnetic stimulation (TBS) significantly alters motor cortical excitability, as evidenced by changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) after applying intermittent (iTBS) and continuous TBS (cTBS) in a study that recorded somatosensory-evoked potentials (SEPs) and high-frequency oscillations (HFOs).

The study found that iTBS increased MEPs and SICI, while cTBS decreased them, indicating that TBS can effectively modulate cortical excitability, with changes in HFOs potentially linked to the same mechanisms affecting SICI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency oscillations change in parallel with short-interval intracortical inhibition after theta burst magnetic stimulation. Murakami, T., Sakuma, K., Nomura, T., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10113132/

A systematic review of the neurobiological effects of theta ... Theta burst stimulation (TBS) is associated with the modulation of a range of clinical, cognitive, and behavioural outcomes, but specific ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2215036625002020

Theta burst stimulation of temporo-parietal cortex regions ... Single-case studies, proof-of-concept studies, and small controlled trials have demonstrated the potential effectiveness of inhibitory 1 Hz repetitive ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2825296

Theta Burst Stimulation Protocols for Schizophrenia The primary outcome of this study was improvement in scores related to negative symptoms (Scale for the Assessment of Negative Symptoms [SANS] ...

4. link.springer.com link.springer.com/article/10.1007/s00429-023-02634-x

A systematic review of the neurobiological effects of theta- ... Theta burst stimulation (TBS) is associated with the modulation of a range of clinical, cognitive, and behavioural outcomes, but specific ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11638604/

Effects of parietal iTBS on resting-state effective connectivity ... Although intermittent theta burst stimulation (iTBS) has shown effectiveness in addressing working memory (WM) deficits in individuals with ...

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

Safety of Theta Burst Transcranial Magnetic Stimulation Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS, as well as intensity dosing studies to assess ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21221011/

Safety of theta burst transcranial magnetic stimulation - PubMed TBS has the theoretical potential of conferring an even higher risk of seizure than other repetitive transcranial magnetic stimulation protocols because it ...

9. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

10. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2015.00029/full

Safety and tolerability of theta burst stimulation vs. single ... Our comparative analysis showed that TBS appears to be as safe as sp/ppTMS in terms of AE rate and severity.