Transcranial Magnetic Stimulation for Healthy Subjects

Overseen By John A Westbrook, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Psychoactive medications

Disqualifiers: Drug abuse, Psychiatric illness, Epilepsy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines changes in the brain's flexibility during challenging thinking tasks and when receiving transcranial magnetic stimulation, a non-invasive procedure using magnetic fields to stimulate nerve cells. It compares different types of stimulation, including a sham version, to assess their effects on brain activity. The trial seeks healthy adults aged 18-45 with no mental or physical illnesses, normal vision, and fluency in English. Participants should be comfortable with MRI scans and two stimulation sessions. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on brain function and stimulation techniques.

Will I have to stop taking my current medications?

If you are currently taking psychoactive medication, you cannot participate in this trial. The protocol does not specify about other medications, but it seems you should not be on any medications that could affect brain activity.

What prior data suggests that transcranial magnetic stimulation is safe for healthy subjects?

Research has shown that transcranial magnetic stimulation (TMS), including both intermittent and continuous theta burst stimulation, is generally well-tolerated. Studies have found these TMS methods to be safe and effective for treating conditions like depression, indicating a strong safety record.

Safety reviews have found intermittent theta burst stimulation to be as safe as regular repetitive TMS, with no serious side effects reported. Similarly, continuous theta burst stimulation has been used in many studies without major safety issues.

Both methods use magnetic fields to stimulate brain cells. Some individuals might experience mild headaches or scalp discomfort, but these effects usually resolve quickly. Overall, existing research supports the safety of these treatments in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of Transcranial Magnetic Stimulation (TMS) because it offers a non-invasive way to modulate brain activity, potentially benefiting conditions like depression and anxiety. Unlike traditional treatments that often involve medication, TMS uses magnetic fields to stimulate nerve cells in the brain, providing a unique and direct approach to altering brain function. This trial is particularly intriguing as it explores different stimulation patterns—intermittent and continuous theta burst stimulation—each with distinct effects on brain activity. By understanding how these patterns influence the right frontal eye field, researchers hope to uncover new insights that could lead to more effective, personalized treatment options.

What evidence suggests that this trial's treatments could be effective for brain flexibility?

This trial will compare different types of theta burst stimulation. Research has shown that intermittent theta burst stimulation (iTBS), which participants in this trial may receive, can quickly and effectively alleviate depression symptoms, especially when targeted at specific brain areas. It may also enhance motor skills and reduce muscle tension in the arms. Another option in this trial, continuous theta burst stimulation (cTBS), has been found to boost brain activity and assist with mental health issues like auditory hallucinations. Both iTBS and cTBS appear to positively affect brain function, prompting further study. ^{6 7 8 9 10}

Who Is on the Research Team?

John A Westbrook, PhD

Principal Investigator

Rutgers University

Are You a Good Fit for This Trial?

This trial is for healthy, neurologically normal adults aged 18-45 who speak English fluently and have at least a high school education. Participants must have normal vision or corrected-to-normal vision, be willing to follow the MRI and stimulation protocol, and commit to the study duration.

Inclusion Criteria

I am willing to follow the MRI and stimulation protocol exactly.

I am fluent in English.

I am healthy with no diagnosed mental or physical illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Theta-burst Stimulation

Participants receive either sham, continuous, or intermittent theta-burst stimulation to the right frontal eye field in a cross-over design

1 session per stimulation type

3 visits (in-person)

Cognitive Task Performance

Participants perform control-demanding cognitive tasks to assess the effects of stimulation on cognitive control and subjective effort

Immediately after each stimulation session

Follow-up

Participants are monitored for safety and effectiveness after stimulation

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The study is testing how the brain's flexibility responds during challenging cognitive tasks by using transcranial magnetic stimulation (TMS), along with monitoring through electroencephalography (EEG) and MRI scans in healthy young adults.

How Is the Trial Designed?

Group I: Intermittent theta burst stimulation Active Control 1 Intervention

In a cross-over design, all participants will, in one session, receive intermittent theta burst stimulation, to the right frontal eye field. Session order will be counter-balanced across participants, and stimulation protocol will be blinded to participants and the Investigator until after data collection is complete.

Group II: Continuous theta burst stimulation Active Control 1 Intervention

In a cross-over design, all participants will, in one session, receive continuous theta burst stimulation, to the right frontal eye field. Session order will be counter-balanced across participants, and stimulation protocol will be blinded to participants and the Investigator until after data collection is complete.

Group III: Sham theta burst stimulation Placebo Group 1 Intervention

In a cross-over design, all participants will, in one session, receive sham theta burst stimulation, to the right frontal eye field. Session order will be counter-balanced across participants, and stimulation protocol will be blinded to participants and the Investigator until after data collection is complete.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

In a study involving 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

In a study involving 14 healthy subjects, repetitive transcranial magnetic stimulation (rTMS) at 20 Hz on the left prefrontal cortex significantly improved cognitive processing, as shown by decreased P3 latencies and faster reaction times.

The study demonstrated that rTMS has a measurable effect on cognitive processing, while single TMS at 1 Hz did not show any significant impact, highlighting the efficacy of rTMS over traditional stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of transcranial magnetic stimulation on cognitive processing: an event-related potential study. Evers, S., Böckermann, I., Nyhuis, PW.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

In a study involving 15 healthy participants, both 600 and 1200 pulses of 5-Hz rTMS significantly increased motor cortex excitability immediately and 30 minutes after stimulation, indicating its efficacy in enhancing cortical activity.

However, there was no significant difference in the effects of the two pulse conditions, suggesting a potential ceiling effect where increasing the number of pulses beyond a certain point does not further enhance cortical excitability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of different pulse numbers of transcranial magnetic stimulation on motor cortex excitability: Single-blind, randomized cross-over design. Tang, ZM., Xuan, CY., Li, X., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) was found to be safe for a patient with an implanted subdural cortical electrode, showing no serious adverse effects during treatment.

Ex-vivo experiments indicated that rTMS caused only a slight increase in coil temperature and no displacement of the electrodes, suggesting that rTMS can be safely applied in clinical settings for patients with such implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case. Phielipp, NM., Saha, U., Sankar, T., et al.[2019]

Repetitive magnetic stimulation (rTMS) is a non-invasive and painless technique that can effectively activate specific areas of the brain, making it useful for studying language, memory, and visual perception.

rTMS shows potential therapeutic benefits for conditions like movement disorders and depression, but there are safety considerations regarding its potential to induce seizures, which are addressed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. Brandt, SA., Ploner, CJ., Meyer, BU.[2019]

High frequency rTMS at 25 Hz significantly decreased motor thresholds and reduced the duration of the silent period in the motor cortex of 16 healthy young adult males, indicating increased cortical excitability.

The effects of rTMS lasted for at least 30 minutes after treatment, suggesting potential for therapeutic applications in enhancing brain plasticity, although the effects returned to baseline within 2 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation. Khedr, EM., Rothwell, JC., Ahmed, MA., et al.[2008]

In a study involving 10 healthy volunteers, repetitive transcranial magnetic stimulation (rTMS) at varying intensities (80-120% of muscle twitch threshold) showed that higher rTMS intensity inversely correlated with blood flow in the stimulated prefrontal cortex and other brain regions, indicating a unique response compared to motor cortex stimulation.

Higher intensity rTMS also led to increased blood flow in distant brain areas like the anterior cingulate and cerebellum, suggesting that stronger stimulation may enhance therapeutic effects for neuropsychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: II. Effects of prefrontal cortex rTMS. Speer, AM., Willis, MW., Herscovitch, P., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

In a study involving 27 healthy right-handed subjects, ipsilateral repetitive transcranial magnetic stimulation (rTMS) before motor training negatively affected finger tracking performance, while contralateral rTMS showed no significant impact.

The results suggest that ipsilateral rTMS may disrupt motor performance temporarily, indicating potential differences in how rTMS could affect individuals with abnormal brain function, such as stroke patients, by possibly enhancing performance in their affected hand.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS combined with motor learning training in healthy subjects. Carey, JR., Fregni, F., Pascual-Leone, A.[2007]

Repetitive transcranial magnetic stimulation (rTMS) significantly improved motor function in stroke patients within the first month after treatment, particularly in upper limb function, as shown by various motor functional scores assessed over time.

The benefits of rTMS on upper extremity function were observed to last for up to one year, indicating its potential as a long-term therapeutic intervention for motor recovery after stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of repetitive transcranial magnetic stimulation (rTMS) after acute stroke: A one-year longitudinal randomized trial. Guan, YZ., Li, J., Zhang, XW., et al.[2021]

In a study with 12 healthy volunteers, 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the left motor cortex slowed down responses of the right hand, indicating that rTMS can affect motor performance.

The effects of rTMS were specific to the stimulated motor areas, as rTMS of the left somatosensory cortex did not impact hand responses, suggesting that the observed behavioral changes are linked to motor cortex excitability rather than general sensory processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slow frequency repetitive transcranial magnetic stimulation affects reaction times, but not priming effects, in a masked prime task. Schlaghecken, F., Münchau, A., Bloem, BR., et al.[2019]

In a study involving 15 chronic stroke patients, five sessions of low-frequency repetitive transcranial magnetic stimulation (rTMS) on the unaffected hemisphere significantly improved motor function in the affected hand for up to 2 weeks, compared to a sham treatment.

The study found that this increased rTMS treatment did not lead to any cognitive side effects or increased risk of seizures, indicating it is a safe intervention for enhancing motor recovery in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Fregni, F., Boggio, PS., Valle, AC., et al.[2022]

Citations

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Interindividual variability in response to continuous theta-burst ... We used complete-linkage cluster analysis to identify healthy subpopulations with distinct responses to continuous theta-burst stimulation (cTBS).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X15008967

Efficacy and Time Course of Theta Burst Stimulation in ... ITBS applied for 190 s significantly increases cortical excitability up to 60 min with a mean maximum potentiation of 35.54 ± 3.32%.

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

Theta burst stimulation for depression: a systematic review ... The current study outcomes included the response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, ...

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1446849/full

The efficacy and safety of continuous theta burst ... Preliminary findings have suggested that cTBS therapy may yield positive results in improving auditory hallucination and minimizing adverse ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6344075/

Effects of continuous theta-burst stimulation of the primary ... Effects of paired continuous theta-burst stimulation (cTBS) on the processing and perception of nociceptive trigeminal input were investigated in 18 healthy ...

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

Safety of Theta Burst Transcranial Magnetic Stimulation There are two commonly used patterns of TBS, continuous (cTBS) and intermittent (iTBS). In cTBS, bursts of 3 pulses at 50 Hz are applied at a frequency of 5 Hz ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1094715923007420

Review Articles Efficacy and Safety of Theta Burst Versus ... Theta burst stimulation (TBS) is more energy- and time-efficient than is standard repetitive transcranial magnetic stimulation (rTMS).

8. 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.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00878787

Theta-burst Transcranial Magnetic Stimulation Stimulation intensity for theta burst will be set at 60% active motor threshold (visit 1), 80% active motor threshold (visit 2), and 80% resting ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4316715/

Safety and tolerability of theta burst stimulation vs. single ... Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 ...