TMS Stimulation for Healthy Subjects

Overseen By Mengsi Li, M.S.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Santa Barbara

Must not be taking: Psychiatric medications

Disqualifiers: Psychiatric disorder, Neurological disease, Seizures, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the brain processes emotions and time to guide actions. Researchers will use functional MRI (fMRI) and transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, to study which brain areas manage emotional events and their timing. Participants will view emotional image sequences and respond to them, helping to identify the brain regions responsible for these tasks. The trial seeks healthy, right-handed individuals who speak English fluently and have normal vision.

As an unphased study, this trial offers participants the chance to contribute to groundbreaking research on brain function and emotional processing.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using psychiatric medication.

What prior data suggests that TMS Stimulation is safe for healthy subjects?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe. The most common side effects include mild headaches and scalp discomfort, which usually resolve quickly. Studies indicate that about 5.5% of participants discontinue TMS due to these side effects. Serious issues, such as the need for psychiatric care or eye problems, are rare but have been reported.

The FDA has approved TMS for treating conditions like obsessive-compulsive disorder, migraines, and smoking cessation. This approval suggests safety for these uses, which adds confidence in its safety, even though this trial uses TMS for a different purpose. Overall, TMS is considered a safe procedure, with no long-term negative effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how Transcranial Magnetic Stimulation (TMS) can influence emotional processing in the brain. Unlike typical treatments that might involve medications or talk therapy, TMS uses magnetic fields to stimulate specific brain areas. This non-invasive technique is being tested for its ability to target the prefrontal cortex, a region involved in emotional regulation, potentially offering new insights into how we process emotions. By combining TMS with fMRI, the study aims to reveal how temporal dynamics of emotional experiences are represented in the brain, possibly paving the way for novel interventions for emotional disorders.

What evidence suggests that TMS Stimulation is effective for tracking emotional and temporal information?

Research has shown that Transcranial Magnetic Stimulation (TMS) yields promising results, particularly in mental health. For instance, one study found that 54% of patients experienced significant symptom improvement. Another study reported a 43% improvement in response rates when patients completed the full treatment. While most research focuses on conditions like depression, these findings suggest TMS can positively impact brain function. In this trial, participants will undergo TMS sessions to explore its effects on processing emotions and time-related information. TMS uses magnetic fields to stimulate brain nerve cells, potentially enhancing the processing of emotions and time-related information. Although limited data exists on using TMS for the specific goals of this study, past results highlight its ability to influence brain activity. ^{6 7 8 9 10}

Who Is on the Research Team?

Regina Lapate, Ph.D.

Principal Investigator

University of California, Santa Barbara

Are You a Good Fit for This Trial?

This trial is for healthy individuals interested in participating in a study that examines how the brain processes emotional and temporal information. Participants should be willing to undergo fMRI scans and transcranial magnetic stimulation (TMS). Specific eligibility criteria are not provided.

Inclusion Criteria

Fluent English speaker

Right-handed

Normal to corrected-to-normal vision

Exclusion Criteria

Sleep deprived (TMS only)

Women with a chance of pregnancy

I have a history of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

fMRI Session

Participants undergo an fMRI session to collect baseline data for emotional and temporal information processing

1 session

1 visit (in-person)

TMS+fMRI Sessions

Participants undergo 3 TMS+fMRI sessions targeting different brain regions to assess causal contributions to task performance

3 sessions

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the TMS+fMRI sessions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMS Stimulation

Trial Overview The study is testing how certain brain regions track emotional and time-related information from dynamic events, using fMRI scans while participants view images. The goal is to understand how this informs actions. TMS will be used to explore the causal role of these regions.

How Is the Trial Designed?

Group I: Duration difference estimation Experimental Treatment 3 Interventions

Participants will view emotional sequences composed of four emotional images. They will be asked to indicate whether the total duration of positive or negative emotional events was longer, by responding with a button press to a contextual cue defining the relevant action (Left vs Right button). The amount of temporal evidence in favor of one valence in a 12-s sequence is varied orthogonally with respect to the (predominant) emotional valence by varying individual picture presentation times. Participants will undergo one fMRI session and 3 TMS+fMRI sessions (2 of the TMS sessions target prefrontal (PFC) sites, and 1 targets a non-PFC control site).

TMS Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as TMS Therapy for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Chronic Pain

Approved in Canada as TMS Therapy for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

University of California, Santa Barbara

Lead Sponsor

Trials

33

Recruited

3,100+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that offers advantages over other methods like vagus nerve stimulation and deep brain stimulation, which require surgery or anesthesia.

TMS has shown promise in various areas, including as a therapeutic tool for neuropsychiatric conditions, a research instrument in neuroscience, and a potential method to enhance cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms and the current state of transcranial magnetic stimulation. George, MS., Nahas, Z., Kozol, FA., et al.[2019]

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

This study mapped the optimal stimulation areas for the thenar and anterior tibial muscles in the primary motor cortex using navigated transcranial magnetic stimulation (TMS) in 59 healthy right-handed subjects, providing important normative data for future clinical assessments.

The research revealed significant variability in optimal stimulation sites, particularly in the anteroposterior direction, which is crucial for understanding how brain plasticity affects functional cortical areas in clinical populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Group-level variations in motor representation areas of thenar and anterior tibial muscles: Navigated Transcranial Magnetic Stimulation Study. Niskanen, E., Julkunen, P., Säisänen, L., et al.[2021]

This study established normative values for navigated transcranial magnetic stimulation (TMS) parameters by analyzing muscle responses from 65 healthy volunteers aged 22 to 81, which can help improve the accuracy of TMS in clinical settings.

The findings provide a modified baseline for TMS-related parameters, including motor thresholds and muscle response latencies, which can assist in distinguishing between true pathophysiological changes and suboptimal stimulation in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor potentials evoked by navigated transcranial magnetic stimulation in healthy subjects. Säisänen, L., Julkunen, P., Niskanen, E., et al.[2009]

A review of 84 single pulse and paired-pulse TMS studies with 1091 Parkinson's disease patients, and 77 repetitive TMS studies with 1137 patients, found a very low risk of adverse events, with no seizures reported.

The overall risk of adverse events from rTMS was 0.040 per patient, with common side effects being mild and transient, such as headaches and scalp pain, indicating that TMS is generally safe for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Vonloh, M., Chen, R., Kluger, B.[2021]

Mild adverse effects (MAEs) from transcranial magnetic stimulation (TMS) occur in about 5% of sessions, with most symptoms like headache and nausea reported after the sessions, particularly during initial treatments.

The study found no significant links between participant characteristics (age and gender) or TMS parameters (frequency and intensity) and the occurrence of MAEs, suggesting that initial participant anxiety may play a role in these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Maizey, L., Allen, CP., Dervinis, M., et al.[2022]

Transcranial magnetic stimulation (TMS) is a valuable non-invasive tool for studying brain function and behavior, particularly in visual perception and cognition, and offers unique advantages over traditional neuropsychological lesion studies.

Despite its usefulness, TMS has limitations, particularly regarding the understanding of its physiological effects, which can lead to ambiguous interpretations of results; combining TMS with functional neuroimaging may help address some of these issues, but challenges remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining transcranial magnetic stimulation and functional imaging in cognitive brain research: possibilities and limitations. Sack, AT., Linden, DE.[2019]

Transcranial magnetic stimulation (TMS) was used to assess the cortical representation of lower-limb muscles in 16 healthy young adults, but it could not reliably identify distinct cortical areas for these muscles.

The study found variability in the topography of muscle representation across individuals, suggesting that while TMS can provide insights into muscle mapping, it may not be effective for precise identification of muscle-specific cortical areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using transcranial magnetic stimulation to map the cortical representation of lower-limb muscles. Davies, JL.[2022]

In a study of 31 right-handed healthy students, transcranial magnetic stimulation (TMS) revealed that motor thresholds increased in the left hemisphere when there was a lack of regular activity in the right hand, indicating a potential impact of muscle use on brain function.

When regular functional loads were resumed on the right hand, the motor thresholds in the left hemisphere decreased, restoring hemispheric asymmetry, suggesting that physical activity can influence motor cortex excitability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of transcranial magnetic stimulation for monitoring of the motor cortex condition in dynamics in healthy subjects]. Gimranov, RF.[2008]

In a study involving 429 pediatric patients undergoing transcranial magnetic stimulation (TMS) for motor and language mapping, most adverse events were benign, with seizures occurring in 5.8% of sessions but not conclusively linked to TMS.

TMS was safely performed in patients with cranial metal, and useful mapping results were achieved in nearly all cases, indicating that TMS is a safe option for functional mapping in pediatric patients with epilepsy or brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided TMS is safe in a predominately pediatric clinical population. Braden, AA., Weatherspoon, SE., Boardman, T., et al.[2022]

The new 'sandwich' TMS setup significantly reduces the magnetic field in the sham condition to about one eighth of that in the active stimulation condition, effectively minimizing unwanted stimulation of both the targeted brain area and neighboring regions.

This innovative design allows researchers to conduct TMS studies with a reliable sham condition, ensuring that subjects cannot distinguish between active and sham stimulation based on external cues, thus improving the overall quality of TMS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation--a sandwich coil design for a better sham. Sommer, J., Jansen, A., Dräger, B., et al.[2021]

Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses magnetic fields to stimulate specific areas of the brain, revealing new insights into brain function and recovery processes, such as those following a stroke.

Over 15 years, TMS has contributed to understanding complex brain functions, including the neuronal basis of consciousness, and is particularly effective when combined with imaging techniques like magnetic resonance imaging (MRI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ferrier Lecture 2004 what can transcranial magnetic stimulation tell us about how the brain works? Cowey, A.[2023]

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can stimulate neurons in the brain, potentially affecting both local and distant neuronal activity.

Despite ongoing research and potential applications, current blinded, sham-controlled trials have not demonstrated that TMS is as effective as conventional treatments for any psychiatric or neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic potential of repetitive transcranial magnetic stimulation in brain disorders]. Fumal, A., Schoenen, J., de Noordhout, AM., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11234753/

Utilization and outcomes of transcranial magnetic ... On balance, we found that the significant and sustained reduction in symptom severity that TMS was able to achieve in this largely treatment- ...

2. uclahealth.org uclahealth.org/news/release/study-finds-possible-early-predictor-successful-transcranial

Study finds possible early predictor of successful ... The new study published this week in Psychiatry Research found that 54% of patients exhibited clinical response (at least a 50% improvement) in ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178121002833

Ten years' data of Transcranial Magnetic Stimulation (TMS) TMS responses of all patients were evaluated 26.1% as response, 29.2% as partial response, and 44.7% as inadequate response. •. It has been determined that MDD ...

4. ir.neuronetics.com ir.neuronetics.com/news-releases/news-release-details/brain-stimulation-highlights-best-practices-optimal-tms

Brain Stimulation Highlights Best Practices for Optimal TMS ... Patients who received a full course of 36 TMS sessions had an 82% greater improvement in remission rate and a 43% greater improvement in response rate.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39549597/

A multisite observational real-world study on the ... The response and remission rates at the end of rTMS therapy as assessed by the HAMD-17 were 53.5 % and 42.8 %, respectively. The dropout rate ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7894543/

Adverse events of repetitive transcranial magnetic ... Serious AE found in trials and case reports are psychiatric hospitalization, suicide ideation, retinal tear and posterior vitreous detachment. Routine ...

7. accessdata.fda.gov accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrfoi__id=11322003&pc=OBP

MAUDE Adverse Event Report: NEURONETICS, INC ... The document i signed outlining the risks of tms included, painful sensations at the treatment site, possible headaches and possible hearing loss.There were no ...

8. nimh.nih.gov nimh.nih.gov/news/media/2020/sarah-h-lisanby-transcranial-magnetic-stimulation-safety-and-risk

Sarah H. Lisanby: Transcranial Magnetic Stimulation Safety ... Most of the common adverse events were headache and scalp discomfort, and 5.5 percent of the patients receiving active TMS discontinued due to ...

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

Transcranial magnetic stimulation The FDA also approved TMS for obsessive-compulsive disorder (OCD), migraines and to help people stop smoking when standard treatments haven't ...

10. cognitivefxusa.com cognitivefxusa.com/blog/side-effects-of-tms-benefits-vs-risks

Side Effects of TMS: Do the Benefits Outweigh the Risks? No long-term negative side effects have been reported and TMS is considered a safe procedure. This applies to the various types of TMS, ranging ...