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

Trial Summary

What is the purpose of this trial?

Transcranial magnetic stimulation (TMS) is increasingly being applied to effectively treat mental illness, however efforts to quantify the effects of TMS on the network architecture of the brain have largely been limited in scope and tied to specific neurologic and psychiatric disorders. The objective of the current work is to build and validate a whole-brain, domain-general model of brain connectivity changes following TMS, based on physical models of the current distribution at the cortex. PUBLIC HEALTH RELEVANCE: This work is relevant to public health because it will provide direct evidence that brain connectivity changes following neuromodulatory TMS vary as a function of the current density at the cortex, which can be used to predict psychiatric symptom change following neuromodulatory TMS.

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 data supports the effectiveness of the treatment Theta Burst Stimulation for Brain Connectivity Changes?

Research shows that intermittent theta burst stimulation (iTBS) can improve motor function and reduce depression symptoms, suggesting it may help with brain connectivity changes. It has been effective in enhancing movement-related brain activity and reducing cortical inhibition, which are important for brain function. ^{1 2 3 4 5}

Is theta burst stimulation safe for humans?

Theta burst stimulation (TBS), including its variations like intermittent theta burst stimulation (iTBS), is generally considered safe for humans. Most adverse events are mild, occurring in about 5% of people, but there is a small risk of seizures, so it should be used with caution. ^{1 6 7 8 9}

How is intermittent theta burst stimulation (iTBS) different from other treatments?

Intermittent theta burst stimulation (iTBS) is unique because it uses magnetic pulses to stimulate the brain, which can help improve motor function by influencing brain activity. Unlike traditional treatments, iTBS is non-invasive and specifically targets the brain's motor cortex to enhance recovery and reduce inhibition in neural networks. ^{1 2 4 10 11}

Research Team

Nicholas L Balderston

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. Estonia 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. [2020]

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

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Intermittent θ burst stimulation over primary motor cortex enhances movement-related β synchronisation. [2011]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation to the Primary Motor Cortex Reduces Cortical Inhibition: A TMS-EEG Study. [2021]

5. United States 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). [2022]

6. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

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

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The After-Effect of Accelerated Intermittent Theta Burst Stimulation at Different Session Intervals. [2022]