Transcranial Magnetic Stimulation During Cognitive Tasks for Healthy Subjects

Overseen By Aaron Mclnnes, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Minnesota

Must not be taking: Seizure medications

Disqualifiers: Psychiatric disorder, Epilepsy, Neurological condition, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 2

Duration: 2 sessions

25 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently using or have recently stopped using medications that can increase the risk of seizure.

Will I have to stop taking my current medications?

The trial excludes people who are currently using medications that can increase the risk of seizure, so you may need to stop taking such medications to participate.

What data supports the idea that Transcranial Magnetic Stimulation During Cognitive Tasks for Healthy Subjects is an effective treatment?

The available research shows that Transcranial Magnetic Stimulation (rTMS) can improve cognitive processing and attention in healthy subjects. One study found that rTMS significantly decreased reaction time and improved cognitive processing when applied to the left prefrontal cortex. Another study showed that rTMS improved attentional function by reducing reaction time and errors in performance tests. These findings suggest that rTMS can enhance certain cognitive functions in healthy individuals. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation, rTMS, Repetitive Transcranial Magnetic Stimulation?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive processing and attentional function in healthy subjects. Studies found that high-frequency rTMS applied to specific brain areas, like the left prefrontal cortex, can lead to faster reaction times and fewer errors in cognitive tasks. ^{1 2 3 4 5}

What safety data exists for transcranial magnetic stimulation?

Safety data for transcranial magnetic stimulation (TMS) and its repetitive form (rTMS) indicate that while it is generally safe, there are potential risks and side effects. Known risks include the possibility of inducing seizures, with 7 cases reported by 1996. Mild adverse effects such as headaches and nausea have been observed, and discomfort during stimulation can affect task performance. Guidelines have been developed to ensure safe use, including limits on stimulation parameters and monitoring of subjects. Studies have shown that when applied within these guidelines, TMS is relatively safe for healthy subjects, with no significant changes in neurological, cognitive, or motor functions observed in some trials. ^{6 7 8 9 10}

Is transcranial magnetic stimulation (TMS) safe for healthy humans?

Transcranial magnetic stimulation (TMS) is generally considered safe for healthy people, but it can cause mild side effects like headaches and nausea. There is a small risk of seizures, especially with repetitive TMS (rTMS), but following safety guidelines can minimize this risk. Some studies have shown no adverse effects on neurological or cognitive functions when TMS is used within recommended limits. ^{6 7 8 9 10}

Is transcranial magnetic stimulation a promising treatment for improving cognitive tasks in healthy people?

Yes, transcranial magnetic stimulation (TMS) is a promising treatment for improving cognitive tasks in healthy people. Studies show that TMS can enhance cognitive processing, improve attention, and reduce reaction times. It works by stimulating specific areas of the brain, which can lead to better performance in tasks that require thinking and memory. ^{1 2 3 4 11}

How is transcranial magnetic stimulation during cognitive tasks different from other treatments?

Transcranial magnetic stimulation (TMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, which can enhance cognitive processing and attention in healthy individuals. Unlike other treatments that might involve medication or invasive procedures, TMS is non-invasive and can target brain regions directly involved in cognitive tasks. ^{1 2 3 4 11}

What is the purpose of this trial?

The study will examine whether the benefits of brain stimulation on mental functioning can be enhanced if an individual is actively engaging the target brain networks while receiving brain stimulation. The study includes two separate sessions and people will complete either a cognitive task or a perceptual task while receiving transcranial magnetic stimulation. The study will measure change in brain function with EEG.

Research Team

Alik Widge, MD, PhD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for healthy individuals aged between 18 and 65. Participants should not be pregnant, have metal in their head (except dental fillings), diagnosed psychiatric disorders, epilepsy or history of seizures, recent concussions, adverse reactions to TMS/MRI, neurological conditions like stroke or tinnitus, or implanted medical devices.

Inclusion Criteria

Healthy controls

Exclusion Criteria

Currently pregnant

Any metal in the head (excluding mouth)

I have epilepsy or have had a seizure before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive transcranial magnetic stimulation while engaging in cognitive or perceptual tasks

2 sessions

2 visits (in-person)

Follow-up

Participants are monitored for changes in brain function using EEG after TMS

1 week

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The study tests if engaging in cognitive or perceptual tasks while receiving transcranial magnetic stimulation (TMS) can enhance mental function. It involves two sessions where brain function changes are measured with EEG during the application of TMS.

Participant Groups

Group I: Healthy control Experimental Treatment 1 Intervention

All participants receive the same procedures

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

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]

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]

In a study involving 27 healthy subjects, 10 Hz repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex significantly improved reaction times and reduced commission errors in attention tasks, indicating enhanced attentional function.

The active rTMS also led to decreased resting motor threshold and short-interval intracortical inhibition, suggesting changes in neurophysiological activity associated with the stimulation, while not affecting motor evoked potentials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attentional and neurophysiologic effects of repetitive transcranial magnetic stimulation. Kim, YW., Cui, JX., Jin, SL., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) applied to the right or left dorsolateral prefrontal cortex (DLPFC) negatively impacted performance on a verbal working memory task, indicating a potential temporary disruption of cognitive function.

The study revealed that rTMS not only reduced regional cerebral blood flow (rCBF) at the stimulation site but also affected distant brain regions, suggesting that rTMS can create temporary functional lesions in neural networks, leading to observable behavioral changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation. Mottaghy, FM., Krause, BJ., Kemna, LJ., et al.[2022]

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) applied to the left dorsolateral prefrontal cortex can lead to significant cognitive improvements, particularly in patients with psychiatric or neurological disorders, compared to healthy volunteers.

The most effective stimulation parameters were found to be 10, 15, or 20 Hz over 10-15 sessions, with patients showing greater cognitive gains than healthy individuals, highlighting the need for further research to understand the underlying mechanisms and effects in various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: a systematic review. Guse, B., Falkai, P., Wobrock, T.[2022]

In a study involving 6 healthy subjects, repeated short trains of rapid-rate transcranial magnetic stimulation (rrTMS) at 20 Hz and slightly above motor threshold were found to be safe, with no adverse effects on neurological, cognitive, or motor functions.

The study observed transient increases in motor evoked potentials (MEPs) in some subjects, suggesting that rrTMS may enhance cortical excitability, indicating its potential utility in studying cognitive and motor functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid rate transcranial magnetic stimulation--a safety study. Jahanshahi, M., Ridding, MC., Limousin, P., et al.[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]

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]

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 healthy subjects performing a verbal working memory task, it was found that discomfort from transcranial magnetic stimulation (TMS) correlated with increased error rates, indicating that side effects can negatively impact task performance.

The results highlight the need for researchers to control for TMS side effects in cognitive neuroscience studies to avoid misinterpretation of findings, as discomfort can bias the outcomes of the experiments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of transcranial magnetic stimulation biased task performance in a cognitive neuroscience study. Abler, B., Walter, H., Wunderlich, A., et al.[2019]

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]

References

1. United States 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. [2019]

2. England pubmed.ncbi.nlm.nih.gov

The impact of transcranial magnetic stimulation on cognitive processing: an event-related potential study. [2019]

3. Singapore pubmed.ncbi.nlm.nih.gov

Attentional and neurophysiologic effects of repetitive transcranial magnetic stimulation. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation. [2022]

5. Austria pubmed.ncbi.nlm.nih.gov

Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: a systematic review. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Rapid rate transcranial magnetic stimulation--a safety study. [2019]

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

Side effects of repetitive transcranial magnetic stimulation. [2005]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. [2022]

9. Ireland 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. [2022]

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

Side effects of transcranial magnetic stimulation biased task performance in a cognitive neuroscience study. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Effect of different pulse numbers of transcranial magnetic stimulation on motor cortex excitability: Single-blind, randomized cross-over design. [2020]