TMS Brain Signal Measurement in Healthy Subjects

Overseen By David J Levinthal, MD PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Antiepileptics, Clozapine, Amphetamines, others

Disqualifiers: Psychosis, Head injury, Pregnancy, Diabetes, 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: Unknown

155 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking antiepileptic medications or certain substances like Clozapine, Chlorpromazine, amphetamines, or others that lower the seizure threshold, you will need to stop taking them to participate in this trial.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) and its variations?

Research shows that Theta Burst Stimulation (TBS), a form of Transcranial Magnetic Stimulation (TMS), can effectively change brain activity by modulating excitability in the motor cortex, which is the part of the brain that controls movement. However, the response to TBS can vary between individuals, and repeated applications may not always have a simple cumulative effect. ^{1 2 3 4 5}

Is TMS safe for healthy subjects?

TMS, including its variations like theta burst stimulation (TBS), is generally considered safe, with most side effects being mild and occurring in about 5% of cases. However, there is a small risk of seizures, especially with TBS, so it should be used cautiously. ^{6 7 8 9 10}

How is TMS different from other treatments for brain conditions?

Transcranial magnetic stimulation (TMS) is unique because it uses magnetic fields to noninvasively stimulate brain neurons, unlike other treatments that might involve medication or surgery. It is particularly novel in its ability to target specific brain areas and is being explored for its effects on brain activity and excitability, which could lead to personalized interventions. ^{2 3 11 12 13}

What is the purpose of this trial?

This is an exploratory study that will determine and standardize how best to record gastric evoked potentials (GEPs) elicited by a non-invasive method of brain stimulation (Transcranial Magnetic Stimulation, TMS), by optimizing the TMS parameters and cortical sites necessary to evoke GEPs.

Research Team

David J Levinthal, MD PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for healthy individuals interested in participating in a study to understand how the brain can influence stomach functions. Specific eligibility criteria are not provided, but typically participants should be free from any medical conditions that could interfere with the study.

Exclusion Criteria

History of psychosis or altered cognitive status

Presence of implantable devices, such as a pacemaker or nerve stimulator

I have a history of head injury, stroke, seizures, or fainting.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exploratory Study

Determine and standardize how best to record gastric evoked potentials (GEPs) using Transcranial Magnetic Stimulation (TMS)

Multiple study sessions spanning up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after the exploratory study

4 weeks

Treatment Details

Interventions

• Transcranial Magnetic Stimulation (TMS)

Trial Overview The study is testing a non-invasive brain stimulation technique called Transcranial Magnetic Stimulation (TMS) to see how it affects signals going to the stomach. The goal is to find out the best settings and areas of the brain to use for this method.

Participant Groups

Group I: All participants Experimental Treatment 1 Intervention

All participants

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

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 17 healthy older participants, there was a significant correlation between changes in motor evoked potentials (MEPs) and early TMS-evoked EEG potentials (TEPs) after intermittent Theta Burst Stimulation (iTBS) to the left primary motor cortex, indicating a relationship between corticospinal and cortical excitability.

While MEP amplitudes increased significantly after iTBS, TEP responses did not show significant changes, suggesting that the effects of iTBS on cortical activity (as measured by TEPs) are more complex and may not directly reflect changes in motor output.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects. Gedankien, T., Fried, PJ., Pascual-Leone, A., et al.[2019]

In a study involving nine healthy right-handed subjects, continuous theta burst stimulation (cTBS) inhibited motor-evoked potential (MEP) amplitudes, while intermittent theta burst stimulation (iTBS) facilitated them, but neither showed significantly stronger effects compared to conventional rTMS protocols.

The study found that the type of pulse waveform and current direction did not significantly influence the effects of TBS, indicating that TBS's efficacy is consistent across different configurations, which helps clarify the mechanisms of transcranial magnetic stimulation on the motor cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation protocols on human motor cortex excitability. Zafar, N., Paulus, W., Sommer, M.[2008]

The study found that while single pulse transcranial magnetic stimulation (TMS) produces consistent cortical responses, the effects of theta-burst stimulation (TBS) protocols on brain activity are highly variable and not reliably reproducible across different sessions.

Most measures of TBS effects did not show significant differences from sham stimulation, indicating that the assumed mechanisms of TBS-induced changes in cortical excitability may need to be re-evaluated, highlighting the need for further research into the underlying mechanisms and reproducibility of TBS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of cortical response modulation induced by intermittent and continuous theta-burst stimulation of the human motor cortex. Ozdemir, RA., Boucher, P., Fried, PJ., et al.[2021]

In a study involving 36 participants, it was found that the intensity of transcranial magnetic stimulation (TMS) significantly affects the plasticity response in the primary motor cortex, with higher intensities (150% of resting motor threshold) yielding greater depression effects from continuous theta burst stimulation (cTBS).

For intermittent theta burst stimulation (iTBS), the most effective probing intensity was at 110% of resting motor threshold, indicating that different intensities are crucial for accurately assessing neuroplasticity responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex. Goldsworthy, MR., Vallence, AM., Hodyl, NA., et al.[2017]

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]

In a study of 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

Transcranial magnetic stimulation (TMS) is safe to use with implanted deep brain stimulation (DBS) devices at low to moderate intensities, as no movement or temperature increase was observed during stimulation at 0.2 Hz with 100% intensity for 1 hour.

However, caution is advised when using high-intensity TMS (over 50%) near looped DBS leads, as it can exceed the safety limit for charge density, potentially leading to electrical tissue injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. Shimojima, Y., Morita, H., Nishikawa, N., et al.[2010]

Theta-burst transcranial magnetic stimulation (TBS) is safe and well tolerated in patients with major depression, based on a study involving 33 participants over 10 consecutive days.

The study suggests that TBS may have antidepressant effects, and increasing stimulation parameters does not lead to more side effects, potentially enhancing its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. Chistyakov, AV., Rubicsek, O., Kaplan, B., et al.[2019]

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]

Transcranial magnetic stimulation (TMS), specifically continuous theta-burst stimulation (cTBS), has been shown to reduce glutamate concentration in the brain, indicating a potential mechanism for its physiological effects.

Using advanced 7T MRI technology, the study found that cTBS led to a decrease in glutamate levels in the ipsilateral hemisphere, while no significant changes were observed in the contralateral hemisphere or in sham stimulation, suggesting targeted effects of cTBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glutamate-Weighted Magnetic Resonance Imaging (GluCEST) Detects Effects of Transcranial Magnetic Stimulation to the Motor Cortex. Cember, ATJ., Deck, BL., Kelkar, A., et al.[2022]

Transcranial magnetic stimulation (TMS) combined with high-resolution electroencephalography (EEG) effectively traced the spread of cortical activation in healthy volunteers, revealing specific activation patterns in both the stimulated and contralateral cortices.

The study found that stimulation at different sites in the left sensorimotor cortex led to varying responses in the contralateral cortex, with consistent activation detected approximately 22 milliseconds after stimulation, indicating the potential for TMS to map brain activity with high precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipsi- and contralateral EEG reactions to transcranial magnetic stimulation. Komssi, S., Aronen, HJ., Huttunen, J., et al.[2022]

Transcranial magnetic stimulation (TMS) is being explored as a tool to study motor dysfunctions in psychiatric disorders, with preliminary findings suggesting it could help identify markers for these conditions.

Despite challenges like small sample sizes and inconsistent methodologies, TMS shows promise for expanding our understanding of psychiatric disorders beyond motor functions to include cognitive processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: studying motor neurophysiology of psychiatric disorders. Maeda, F., Pascual-Leone, A.[2018]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation protocols on human motor cortex excitability. [2008]

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

Reproducibility of cortical response modulation induced by intermittent and continuous theta-burst stimulation of the human motor cortex. [2021]

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

Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex. [2017]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020]

8. England pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. [2010]

9. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. [2019]

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

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

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

Glutamate-Weighted Magnetic Resonance Imaging (GluCEST) Detects Effects of Transcranial Magnetic Stimulation to the Motor Cortex. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Ipsi- and contralateral EEG reactions to transcranial magnetic stimulation. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: studying motor neurophysiology of psychiatric disorders. [2018]