Brain Connectivity Techniques for Healthy Subjects

Overseen By Gabriel Fadel, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Neurological medications

Disqualifiers: Epilepsy, Heart disease, Mental disorders, others

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

Compensation: Varies

Number of Visits: 4

Duration: 3 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different areas of the brain connect and communicate in healthy individuals. Researchers use a non-invasive technique called paired associative stimulation (PAS), which delivers tiny magnetic pulses to two brain areas. The goal is to determine if this alters communication between these areas. Participants should be right-handed, have normal hearing and vision, and no metal in their body. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research on brain communication.

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

The trial excludes participants who are on medications that influence brain function, so you may need to stop taking such medications to participate. However, the protocol does not specify a washout period.

What prior data suggests that these brain connectivity techniques are safe for healthy subjects?

Previous studies have shown that paired associative stimulation (PAS) is safe and well-tolerated, with no major side effects. Some research indicates that PAS can easily combine with other treatments without issues.

Single-pulse transcranial magnetic stimulation (spTMS) also maintains a strong safety record. Participants might experience mild headaches or localized pain after a session, but these are usually manageable. Serious side effects, such as seizures, are rare and can often be prevented with proper precautions.

Both treatments are non-invasive, meaning they don't involve surgery or entering the body, which generally enhances their safety. Overall, these methods have been used safely in various research and medical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it's exploring innovative brain connectivity techniques, like paired associative stimulation (PAS) and single-pulse transcranial magnetic stimulation (spTMS). Unlike current methods that often focus on treating specific brain conditions, this trial is investigating how these techniques can enhance our understanding of normal brain functions in healthy individuals. By leveraging advanced MRI and TMS-EEG methodologies, the trial aims to uncover new insights into brain plasticity and connectivity, potentially paving the way for future treatments that could enhance cognitive function or aid in recovery from neurological conditions.

What evidence suggests that these brain connectivity techniques are effective for studying brain connectivity?

Research has shown that paired associative stimulation (PAS) can improve connections between different parts of the brain. Studies have found that PAS aids in motor skill recovery and enhances the brain's ability to send signals to muscles, potentially strengthening connections between brain areas. In this trial, participants will undergo PAS sessions to explore its effects on brain connectivity.

Research supports single-pulse transcranial magnetic stimulation (spTMS) in affecting brain activity. It serves as a tool to study brain networks and their connections. Participants in this trial will also experience spTMS sessions to determine its impact on brain activity. Together, these techniques may help researchers understand and enhance communication between different brain regions. ^{2 6 7 8 9}

Who Is on the Research Team?

Tommi Raij, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for right-handed, healthy individuals with normal hearing and vision who can understand and give informed consent. It's not suitable for those who don't meet these specific criteria.

Inclusion Criteria

I am right-handed.

My hearing and vision, with aids if necessary, are normal.

I understand the study and can give my consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Assessment

Participants undergo MRI scans and a TMS session to determine motor thresholds

1 visit

1 visit (in-person)

Treatment

Participants receive TMS-EEG procedures with ccPAS over three visits, each with a different asynchrony condition

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in EEG effective connectivity and task performance

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Paired associative stimulation (PAS)
• Single-pulse transcranial magnetic stimulation (spTMS)

Trial Overview The study investigates brain connectivity in healthy people using non-invasive methods: MRI scans, single-pulse TMS, and paired associative stimulation. Researchers will explore how different timing of TMS pulses affects brain region connections.

How Is the Trial Designed?

Group I: Healthy Participants Experimental Treatment 3 Interventions

All participants will be scheduled for a minimum of four separate visits. The first visit will consist of MRI scanning sessions (including T1 and T2 structural MRI, diffusion MRI, and resting-state fMRI), followed by a single-pulse TMS session to determine the participant's resting motor threshold. The remaining three visits consist of a series of TMS-EEG runs using the paired associative stimulation (PAS) methodology. Each visit will be restricted to a single asynchrony condition with every participant receiving all three conditions over the course of the three visits. Participants will not be informed of which asynchrony condition they are receiving on any given visit. Some subjects may be invited for additional sessions for the purposes of optimizing TMS, EEG, or MRI parameters, and to assess test-retest reliability.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11130975/

The Effectiveness of Paired Associative Stimulation on ... Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1878747925002569

Paired associative stimulation improves outcomes when ... Original Article. Paired associative stimulation improves outcomes when applied at the subacute stage after incomplete cervical spinal cord ...

3. nature.com nature.com/articles/s41598-019-40474-0

Increasing the frequency of peripheral component in paired ... Here we investigated whether the effectiveness of PAS can be further enhanced. Potentiation of MEPs up to 60 minutes after PAS with PNS ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06246942

NCT06246942 | Physiology of Human Brain Connectivity The purpose of this study is to investigate the effective connectivity between different regions of the human brain in healthy participants, ...

5. mdpi.com mdpi.com/2076-3425/15/5/461

A Methodological Evaluation of Four Different Paired ... Results: PAS-25 with 225 pairings produced a robust enhancement of corticospinal excitability, while PAS-25 with 180 pairings was less effective. Surprisingly, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6718871/

A Systematic Review of Paired Associative Stimulation (PAS ... PAS results in a rapid change in corticomotor excitability (CME) of the corticospinal pathway to the target muscle. This change in CME is ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5447079/

Paired-Associative Stimulation-Induced Long-term ... PAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS ...

8. mdpi.com mdpi.com/2076-3425/13/3/475

Effects of Paired Associative Stimulation on Cortical ... Paired associative stimulation (PAS) increases and decreases cortical excitability in primary motor cortex (M1) neurons, depending on the spike ...

9. frontiersin.org frontiersin.org/journals/rehabilitation-sciences/articles/10.3389/fresc.2023.1200958/full

The effect of paired associative stimulation with a high- ... This study revealed that high PAS is safe and does not show any cardiovascular effects over a 60-min follow-up. An increase in the HF band ...