Theta Burst Stimulation for Brain Connectivity Changes

Overseen By Nicholas L Balderston

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Nicholas Balderston, PhD

Must not be taking: CNS medications

Disqualifiers: Psychiatric disorders, Seizure history, Alcohol/drug problems, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 week

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how Theta Burst Stimulation (TBS), a type of brain stimulation, affects brain connections. Researchers use this technique to determine if changes in brain connectivity can predict improvements in mental health symptoms. Participants will receive either intermittent or continuous TBS, a form of non-invasive brain stimulation, to study these effects. The trial seeks right-handed individuals without significant medical or psychiatric conditions, recent struggles with alcohol or drugs, or metal implants that would interfere with MRI scans. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance mental health treatments.

Will I have to stop taking my current medications?

The trial excludes participants who are taking medications that act on the central nervous system, so you may need to stop taking such medications to participate.

What prior data suggests that this technique is safe?

Research has shown that continuous theta burst stimulation (cTBS) is generally safe and well-tolerated. Studies indicate that cTBS does not increase unexpected or harmful effects, making it a safe option for treating various conditions.

Intermittent theta burst stimulation (iTBS) is also considered safe. In 2018, the FDA approved iTBS for treating major depression, confirming that it meets safety standards for this purpose. However, while iTBS is effective, its safety profile limits its use for longer or more intense sessions.

Both cTBS and iTBS typically do not cause serious side effects. They are well-tolerated, allowing most people to undergo these treatments without major issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about theta burst stimulation (TBS) because it offers a new way to influence brain connectivity, which is crucial for treating various neurological conditions. Unlike traditional treatments that may rely on medications or invasive procedures, TBS uses a non-invasive magnetic coil to deliver short bursts of stimulation to the brain, potentially leading to faster and more targeted effects. Additionally, the trial explores two different protocols, continuous (cTBS) and intermittent (iTBS), which might offer flexibility in treatment plans depending on individual patient needs. This approach could revolutionize how we enhance brain function with fewer side effects than current options.

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

Research has shown that Intermittent Theta Burst Stimulation (iTBS), one of the treatments in this trial, can quickly and effectively improve depression symptoms, particularly in teenagers. Studies suggest that iTBS alters brain activity, potentially aiding in the treatment of other conditions. Continuous Theta Burst Stimulation (cTBS), another treatment arm in this trial, has been shown to change how different parts of the brain connect and improve certain mental health symptoms, such as hearing voices. Both iTBS and cTBS appear to affect brain networks, which is why researchers are studying them for mental health treatments in this trial. These findings suggest that both types of stimulation could enhance brain function and alleviate mental health symptoms. ^{2 6 7 8 9}

Who Is on the Research Team?

Nicholas L Balderston

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for right-handed individuals who can consent to participate. It's not suitable for those with recent alcohol/drug issues, medical conditions affecting fMRI or TMS safety, metal implants, claustrophobia, severe psychiatric disorders, epilepsy, pregnancy, non-English speakers, CNS medications use or any significant health problems.

Inclusion Criteria

Right-handed

Able to give their consent

Exclusion Criteria

Pregnancy

Any metal in their body which would make having an MRI scan unsafe

I have a history of epilepsy or other neurological issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of either intermittent or continuous theta burst stimulation (iTBS and cTBS) over 3 stimulation days, with 5 sessions per day.

1 week

3 visits (in-person)

Follow-up

Participants are monitored for changes in resting state functional connectivity and working memory performance 24 hours after each dose.

1 week

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Continuous Theta Burst Stimulation
• Intermittent Theta Burst Stimulation

Trial Overview The study tests how brain connectivity changes after two types of Transcranial Magnetic Stimulation (TMS): Intermittent and Continuous Theta Burst Stimulation. The goal is to create a model predicting changes in brain networks that could help treat psychiatric symptoms.

How Is the Trial Designed?

Group I: Intermittent Theta Burst Stimulation Experimental Treatment 1 Intervention

TBS. A Magventure MagPro 100X stimulator with a B65 figure-8 coil will be used for the TBS sessions. On each of the 3 stimulation days, 5 iTBS sessions will be administered at 30 min intervals.

Group II: Continuous Theta Burst Stimulation Experimental Treatment 1 Intervention

TBS. A Magventure MagPro 100X stimulator with a B65 figure-8 coil will be used for the TBS sessions. On each of the 3 stimulation days, 5 cTBS sessions will be administered at 30 min intervals.

Who Is Running the Clinical Trial?

Nicholas Balderston, PhD

Lead Sponsor

Trials

2

Recruited

240+

Published Research Related to This Trial

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Continuous theta burst stimulation (cTBS) effectively inhibits synaptic transmission in the primary motor cortex for up to 1 hour, demonstrating its potential as a novel neuromodulation technique.

cTBS applied to the left motor cortex increases local GABA levels, indicating enhanced GABAergic activity, while not significantly affecting glutamate/glutamine levels, suggesting a specific mechanism of action for this stimulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. Stagg, CJ., Wylezinska, M., Matthews, PM., et al.[2022]

In a study involving 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

Transcranial magnetic intermittent theta burst stimulation (iTBS) with a prolonged protocol (1200 pulses) significantly increased corticospinal excitability in the targeted primary motor cortex (M1) while inhibiting excitability in the opposite M1 for up to 30 minutes, indicating its potential for modulating motor function.

iTBS1200 also enhanced post-movement beta synchronisation in the stimulated M1, suggesting a link between this brain activity and improved motor output, while not affecting alpha and low gamma rhythms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent θ burst stimulation over primary motor cortex enhances movement-related β synchronisation. Hsu, YF., Liao, KK., Lee, PL., et al.[2011]

In a study involving 31 healthy volunteers, it was found that the effectiveness of intermittent theta burst stimulation (iTBS) in enhancing motor function varies based on the baseline excitability of the primary motor cortex (M1), as indicated by the size of motor evoked potentials (MEPs).

Participants who showed greater facilitation from iTBS had smaller baseline MEPs and exhibited more synchronization in specific EEG oscillations, suggesting that both baseline MEP amplitude and iTBS-evoked beta oscillations are key factors influencing the variability of iTBS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study. Leodori, G., Fabbrini, A., De Bartolo, MI., et al.[2021]

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]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

Intermittent theta burst stimulation (iTBS) applied to the primary motor cortex (M1) significantly reduced cortical inhibition, as evidenced by decreased N100 amplitude in TMS-evoked potentials, indicating enhanced cortical excitability.

The study involved 18 young adults and demonstrated that iTBS specifically affects the M1, leading to changes in motor performance and cortical network dynamics, suggesting potential therapeutic applications for neurological and psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation to the Primary Motor Cortex Reduces Cortical Inhibition: A TMS-EEG Study. Bai, Z., Zhang, J., Fong, KNK.[2021]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

Intermittent theta-burst stimulation (iTBS) can be safely administered in doses of 1,800 pulses per day, with different protocols affecting motor cortical excitability in varying ways.

The protocol with 30-minute intervals between sessions (iTBS600 × 3∗30) not only enhanced cortical excitability the most but also had the longest-lasting effects compared to other protocols tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The After-Effect of Accelerated Intermittent Theta Burst Stimulation at Different Session Intervals. Yu, F., Tang, X., Hu, R., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34670201/

Brain network effects by continuous theta burst stimulation in ... Network connectivity changes after single and repetitive stimulations of cTBS were analyzed.Main results.Using electrophysiological source ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10113132/

A systematic review of the neurobiological effects of theta ... Network based statistical analysis detects changes induced by continuous theta-burst stimulation on brain activity at rest. Front Psychiatry ...

3. nature.com nature.com/articles/s41467-024-51443-1

Theta-burst direct electrical stimulation remodels human ... Theta-burst stimulation (TBS), a patterned brain stimulation technique that mimics rhythmic bursts of 3–8 Hz endogenous brain rhythms, ...

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 consequences (30–33) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2451902224002064

The Neurophysiological Effects of Theta Burst Stimulation ... In this systematic review, we summarize the electrophysiological effects of a single session of TBS measured with EEG and concurrent TMS-EEG in nonclinical ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8617062/

A Systematic Review of the Safety and Tolerability of Theta ... In 2018 the FDA cleared intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex for the treatment of major depressive ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291820302794

Safety Considerations for Cerebellar Theta Burst Stimulation No serious adverse events have been reported for cerebellar TBS. There is no substantial evidence of a tolerable maximal-efficacy stimulation dose in humans.

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

Safety of Theta Burst Transcranial Magnetic Stimulation However, TBS protocols appear to lead to sustained changes in cortical activity lasting well beyond the duration of the TMS application, providing a putative ...

9. nature.com nature.com/articles/s41398-025-03605-y

Modulation of brain oscillations by continuous theta burst ... Continuous theta burst stimulation (cTBS) induces long-lasting depression of cortical excitability in motor cortex. In the present study, ...