Theta-Burst Stimulation for Language Disorders

(TAFE Trial)

Overseen By C. Nikki Arrington, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Georgia State University

Disqualifiers: Learning disability, Hearing deficits, Visual deficits, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how transcranial magnetic stimulation (TMS) affects reading and language skills. TMS uses magnetic fields to briefly influence brain function, and researchers aim to determine when these effects on reading are strongest. The trial compares different types of stimulation, including continuous theta-burst stimulation (cTBS) and intermittent theta-burst stimulation (iTBS), to understand their impact on reading and language tasks. Ideal participants are right-handed, native English speakers with typical reading skills and no history of learning disabilities. As an unphased trial, this study allows participants to contribute to groundbreaking research in understanding brain function and language skills.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that transcranial magnetic stimulation is safe for language and reading studies?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated. The FDA has approved it for treating major depression, confirming its safety for humans. Some studies have compared iTBS to other treatments and found it effective without serious side effects.

For continuous theta burst stimulation (cTBS), reviews suggest it is also safe but should be used carefully due to its relative novelty. Studies on cTBS have not shown major safety concerns, but caution is advised.

Both iTBS and cTBS are types of transcranial magnetic stimulation (TMS) that use magnetic fields to temporarily affect brain function. They have been studied in various settings. Overall, the safety data for both iTBS and cTBS appears promising. However, ongoing monitoring in studies helps ensure their safety for all participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about theta-burst stimulation (TBS) for language disorders because it offers a novel approach using non-invasive brain stimulation. Unlike traditional treatments that might involve medication or speech therapy, TBS uses magnetic pulses to modulate brain activity, potentially enhancing language abilities more directly and rapidly. Specifically, continuous theta-burst stimulation (cTBS) and intermittent theta-burst stimulation (iTBS) are being explored for their distinct effects on brain plasticity, which could lead to improved language processing. This method could provide a faster and more targeted option compared to conventional therapies, which often require lengthy and intensive sessions to achieve noticeable results.

What evidence suggests that this trial's treatments could be effective for language disorders?

This trial will compare intermittent theta burst stimulation (iTBS), continuous theta burst stimulation (cTBS), and sham stimulation. Studies have shown that iTBS can improve language skills, such as those affected by aphasia, by encouraging the brain to adapt and change. It has also benefited social understanding and reduced negative symptoms in people with schizophrenia. Meanwhile, cTBS has helped with understanding language structure. Research suggests that both iTBS and cTBS effectively target specific brain functions, which is promising for treating language disorders. Both types of stimulation use magnetic fields to temporarily alter the function of certain brain areas, aiming to aid reading and language. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with reading and language disorders, as well as healthy control subjects. Participants must be willing to undergo cognitive testing, MRI scans, TMS stimulation, and perform various tasks related to language, reading, and motor skills.

Inclusion Criteria

* Subjects must have a minimum of low average intellectual functioning (\>=80) on at least one subscale on the Wechsler Abbreviated Scale of Intelligence-2 (WASI-2; Wechsler, 2011) to be included.

* Within a normal range of reading skills as \>85 on the Test of Word Reading Efficiency - Second Edition (TOWRE-2; Torgesen et al., 2012) and the Woodcock-Johnson IV Tests of Achievement (WJ-IV; Schrank et al., 2014)

* Individuals with a documented history of learning disability will not be included. This will be determined via demographics questionnaire.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial magnetic stimulation (TMS) and undergo reading, language, and cognitive testing

6 weeks

Weekly visits for TMS and testing

Follow-up

Participants are monitored for changes in reading and language behavior after TMS

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• cTBS
• iTBS
• Sham Stimulation

Trial Overview The study investigates the timing and effects of different types of transcranial magnetic stimulation (iTBS - excitatory; cTBS - inhibitory; Sham Stimulation) on reading speed, ease, accuracy, and overall language behavior.

How Is the Trial Designed?

Group I: iTBS/Sham Experimental Treatment 2 Interventions

Adults age 18-30 with typical reading and language abilities

Group II: cTBS/Sham Experimental Treatment 2 Interventions

Adults age 18-30 with typical reading and language abilities

cTBS is already approved in United States for the following indications:

Approved in United States as cTBS for:

• Major Depressive Disorder (using iTBS protocol)

Who Is Running the Clinical Trial?

Georgia State University

Lead Sponsor

Trials

71

Recruited

33,600+

Published Research Related to This Trial

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]

Theta-burst stimulation appears to significantly reduce the severity of unilateral spatial neglect in stroke patients, based on a systematic review of nine studies involving 148 participants.

Despite the promising results, the evidence is limited and inconsistent due to variations in study protocols and terminology, making it difficult to draw definitive conclusions about its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of theta-burst stimulation on unilateral spatial neglect following stroke: a systematic review. Cotoi, A., Mirkowski, M., Iruthayarajah, J., et al.[2019]

In a study involving 29 patients with major depression, continuous theta-burst transcranial magnetic stimulation (cTBS) did not show a significant overall improvement compared to sham treatment, indicating modest efficacy.

However, patients who were either medication-free or had unchanged medication status experienced a greater reduction in depression scores with active cTBS, suggesting it may be beneficial for those not responding to traditional pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary assessment of the therapeutic efficacy of continuous theta-burst magnetic stimulation (cTBS) in major depression: a double-blind sham-controlled study. Chistyakov, AV., Kreinin, B., Marmor, S., et al.[2018]

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) applied to the left frontal lobe showed significant improvements in language abilities for participants with post-stroke aphasia, as evidenced by moderate to large effect sizes on tests like the Boston Naming Test and Semantic Fluency Test.

The study, involving 36 participants over 3 weeks, demonstrated that iTBS not only enhanced language function but also led to increased brain activation and connectivity, suggesting that this treatment may promote cortical plasticity in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation (iTBS) for Treatment of Chronic Post-Stroke Aphasia: Results of a Pilot Randomized, Double-Blind, Sham-Controlled Trial. Szaflarski, JP., Nenert, R., Allendorfer, JB., et al.[2021]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

Intermittent theta burst stimulation (iTBS) applied to the language-responsive cortex in chronic poststroke aphasia patients led to increased activation in the left inferior frontal gyrus (IFG) and decreased activation in the right IFG, suggesting a shift towards more effective language processing in the left hemisphere.

Although there were no significant changes in grey matter volume, the functional MRI results indicate that iTBS may help improve language fluency by reducing right IFG activity, which is associated with language production, thereby enhancing the use of residual language areas in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia. Griffis, JC., Nenert, R., Allendorfer, JB., et al.[2018]

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]

Continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated in patients with major depressive disorder (MDD) or bipolar depression (BD), with no significant differences in adverse events compared to sham treatment.

However, the meta-analysis of three randomized controlled trials involving 78 participants showed no significant improvement in depression scores or response rates with cTBS compared to sham, indicating that cTBS may not provide a therapeutic advantage for treating major depressive episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. Cai, DB., Qin, XD., Qin, ZJ., et al.[2023]

In a study involving 34 aphasic patients, continuous theta burst stimulation (cTBS) over the right posterior superior temporal gyrus significantly improved language performance compared to sham stimulation, as measured by the Western Aphasia Battery scores.

The mechanism behind these improvements appears to involve decreased intrinsic activity in the right fronto-thalamic-cerebellar circuit and enhanced connectivity in the right temporoparietal region, suggesting a targeted approach to language rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous theta burst stimulation-induced suppression of the right fronto-thalamic-cerebellar circuit accompanies improvement in language performance in poststroke aphasia: A resting-state fMRI study. Zheng, K., Xu, X., Ji, Y., et al.[2023]

Citations

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Advances in theta-burst transcranial magnetic stimulation for ... Aphasia is a language network disorder caused by organic brain lesions, which severely affects patients' daily communication and interaction.

2. sciencedirect.com sciencedirect.com/science/article/pii/S105381192500014X

Continuous theta-burst stimulation demonstrates language ... These findings reveal the specific causal relevance of the language areas for hierarchical syntactic processing, separable from other general cognitive (such ...

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

The efficacy and safety of continuous theta burst ... This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia.

4. gpsych.bmj.com gpsych.bmj.com/content/38/2/e102012

Evaluating the feasibility, safety and efficacy of accelerated ... In this study, we conducted an open-label trial to assess the feasibility, safety and efficacy of the novel 5-day a-cTBS intervention among children with ASD.

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

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

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

Safety of Theta Burst Transcranial Magnetic Stimulation Based on this review, TBS appears to be a safe and efficacious technique. However, given its novelty, it should be applied with caution.

7. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1610016/full

Advances in theta-burst transcranial magnetic stimulation ... Therefore, this article reviews the research progress related to the use of TBS in treating auditory comprehension in aphasia, aiming to provide ...

8. med.stanford.edu med.stanford.edu/content/dam/sm/scsnl/documents/xiao_Et_al_2025.pdf

Personalized Theta Burst Stimulation Enhances Social Skills ... Transcranial magnetic stimulation (TMS) has emerged as a promising treatment modality for various psychiatric and neurological disorders (8,9).

9. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024082823

A systematic review of transcranial magnetic stimulation ... Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms.