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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how to best record brain signals, called gastric evoked potentials (GEPs), using a non-invasive method known as Transcranial Magnetic Stimulation (TMS). The goal is to determine the most effective way to use TMS to measure these signals, potentially advancing research in brain and stomach interactions. Individuals with no history of certain health conditions, such as head injuries or seizures, and who are not on specific medications or substances, might be suitable participants. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in understanding brain and stomach interactions.

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 prior data suggests that this method is safe for measuring brain signals?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe when used according to current guidelines. TMS, a non-invasive treatment, uses magnetic fields to stimulate brain cells and has been used to treat conditions like major depression. Although considered quite safe, there is a small chance of side effects, such as headaches or lightheadedness. Serious side effects are rare. Overall, medical practice views TMS as a well-tolerated treatment option. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) because it offers a non-invasive way to influence brain activity without the need for medication. Unlike other treatments that might involve drugs or surgery, TMS uses magnetic fields to stimulate nerve cells in the brain, which could lead to new insights into brain function and potential treatments for various neurological conditions. This technique is particularly appealing because it targets specific areas of the brain, potentially leading to more precise and effective outcomes with fewer side effects.

What evidence suggests that this method is effective for recording gastric evoked potentials?

Transcranial Magnetic Stimulation (TMS) uses magnetic fields to stimulate the brain. Research has shown that TMS can alter brain function, potentially aiding conditions like depression. Studies have found that TMS influences brain connections, such as those between the front and back parts, altering brain activity. This study tests new methods to measure TMS's impact on brain signals in healthy subjects. Although TMS is already used for certain conditions, this research specifically investigates how TMS might trigger specific brain signals. More studies are needed to fully understand its effects in various situations. ^{2 6 7 8 9}

Who Is on the Research Team?

David J Levinthal, MD PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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

I have diabetes.

History of psychosis or altered cognitive status

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1504727/full

A meta-analysis comparing the effectiveness and safety of ... Objective: This study compares the safety and effectiveness of theta-burst stimulation (TBS) and repetitive transcranial magnetic stimulation (rTMS) for ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10311181/

Effects of repetitive transcranial magnetic stimulation and their ... The results indicated that rTMS induced intrinsic brain activity changes through frontolimbic and cerebellothalamocortical pathways. Another study showed ...

3. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763424001647

Neurophysiological and neuroimaging markers of ... Transcranial magnetic stimulation (TMS) utilizes electromagnetic fields to induce electrical currents and neuronal depolarization in cortical neurons beneath ...

5. nature.com nature.com/articles/s41531-025-01054-4

Effects of two types of repetitive transcranial magnetic ... This study demonstrates that compared to 10Hz-rTMS, iTBS can reduce treatment time while providing superior improvement in functional brain connectivity for PD ...

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

Safety of Theta Burst Transcranial Magnetic Stimulation TMS is considered quite safe if applied within current safety guidelines, however, TMS does pose some risk for adverse side effects (Rossi et al., 2009).

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568715/

Repetitive Transcranial Magnetic Stimulation - StatPearls - NCBI Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive treatment technique used to treat various psychiatric and neurological disorders.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1876201825000632

Efficacy and safety of accelerated transcranial magnetic ... Standard transcranial magnetic stimulation (TMS) has shown moderate efficacy but requires 6–8 weeks of daily sessions. This review evaluates the efficacy, ...

9. fda.gov fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/repetitive-transcranial-magnetic-stimulation-rtms-systems-class-ii-special-controls-guidance

Repetitive Transcranial Magnetic Stimulation (rTMS) Systems This guidance document was developed as a special controls guidance to support the classification of Repetitive Transcranial Magnetic Stimulation (r TMS) ...