Brain Stimulation for Speech Learning

Overseen By David Ostry

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Psychoactive medications

Disqualifiers: Epilepsy, Neurological disorders, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 days

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the brain learns and remembers speech using transcranial magnetic stimulation (TMS). Researchers focus on the roles of different brain areas, such as those for hearing, touch, and movement, in learning and retaining speech skills. Participants will undergo brain stimulation, specifically with continuous theta-burst stimulation (cTBS), while performing speech tasks to assess its impact on their ability to learn and remember. This trial may suit right-handed, fluent English speakers with normal hearing and no speech or reading issues. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research on brain function and speech learning.

Will I have to stop taking my current medications?

The trial excludes participants who are taking psychoactive medications, so you would need to stop taking those to participate. For other medications, the protocol does not specify.

What prior data suggests that this brain stimulation technique is safe for speech learning?

Research has shown that continuous theta-burst stimulation (cTBS) is generally safe. Studies have found that cTBS, used to treat conditions like auditory hallucinations in schizophrenia and tinnitus, does not cause major side effects. For example, one study found that applying cTBS to brain areas involved in hearing and speech was safe and did not impair these functions.

In another study on learning to speak, cTBS was used without any serious side effects. Overall, these findings suggest that cTBS is a safe option for similar research. However, as with any treatment, individual experiences may vary, so discussing any concerns with the study staff or a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how continuous theta-burst stimulation (cTBS) can enhance speech learning by targeting specific brain regions. Unlike traditional speech therapy that focuses on exercises and practice over time, cTBS offers a unique approach by directly stimulating the auditory, somatosensory, or motor cortex. This method could accelerate learning and retention by directly influencing brain activity patterns. The trial aims to uncover how these targeted stimulations improve speech learning, potentially offering a more efficient and effective way to address speech disorders.

What evidence suggests that this trial's treatments could be effective for speech learning?

Studies have shown that continuous theta-burst stimulation (cTBS) can improve speech and sound comprehension. Research indicates that applying cTBS to certain brain areas can significantly enhance speech understanding and conditions like aphasia, which affects speaking and comprehension. Additionally, cTBS is considered safe for hearing and speech perception. In this trial, participants will receive cTBS applied to different brain areas, such as the auditory, somatosensory, or motor cortex, with either altered or unaltered auditory feedback. This approach suggests that targeting specific brain areas with cTBS might aid in learning and remembering new speech patterns. Overall, early findings are promising for using cTBS in learning and retaining speech skills. ^{2 5 6 7 8}

Who Is on the Research Team?

David Ostry

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for right-handed, fluent English speakers with normal hearing and no speech disorders or reading disabilities. It's not suitable for individuals with a cardiac pacemaker, cochlear implant, tinnitus, metal implants in the brain or body, history of epilepsy or severe head injuries, those who are pregnant or on psychoactive medications.

Inclusion Criteria

Right-handed

No speech disorder or reading disability

I have normal hearing.

Exclusion Criteria

Pregnancy

Cardiac pacemaker

Aneurysm clip

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants perform learning tasks with altered or unaltered auditory feedback, followed by cTBS to specific brain regions. This is repeated on day 2.

2 days

2 visits (in-person)

Retention Assessment

Participants return 24 hours after treatment to assess retention of learning.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adaptation
• continuous theta-burst stimulation (cTBS)

Trial Overview The study tests how learning and retaining new ways to speak might change the brain. Participants will undergo continuous theta-burst stimulation (cTBS) to disrupt brain activity and adaptation exercises while their brain function is monitored using fMRI scans and sensory/motor evoked potentials.

How Is the Trial Designed?

Group I: Unaltered auditory feedback + cTBS to somatosensory cortex Experimental Treatment 2 Interventions

Participants will perform learning tasks while receiving unaltered auditory feedback.This procedure will be repeated on day 2. cTBS will be applied to the left hemisphere somatosensory cortex following learning. Participants then leave the laboratory and return 24 hours later to assess retention of learning. If the effects of cTBS are specific to learning, no effect should be observed in these control conditions.

Group II: Unaltered auditory feedback + cTBS to motor cortex control zone Experimental Treatment 2 Interventions

Participants in a control condition will undergo the same procedures using cTBS to a motor cortex control zone in the right hemisphere (associated with the hand muscle first dorsal interosseous). cTBS will be applied following learning and subjects will return 24 hours later to test for retention. This control condition is included as a test for non-specific effects of cTBS stimulation. If the effects of cTBS are specific to learning, no effect should be observed in these control conditions.

Group III: Unaltered auditory feedback + cTBS to motor cortex Experimental Treatment 2 Interventions

Participants will perform learning tasks while receiving unaltered auditory feedback.This procedure will be repeated on day 2. cTBS will be applied to the left hemisphere motor cortex following learning. Participants then leave the laboratory and return 24 hours later to assess retention of learning. If the effects of cTBS are specific to learning, no effect should be observed in these control conditions.

Group IV: Unaltered auditory feedback + cTBS to auditory cortex Experimental Treatment 2 Interventions

Participants will perform learning tasks while receiving unaltered auditory feedback.This procedure will be repeated on day 2. cTBS will be applied to the left hemisphere auditory cortex following learning. Participants then leave the laboratory and return 24 hours later to assess retention of learning. If the effects of cTBS are specific to learning, no effect should be observed in these control conditions.

Group V: Altered auditory feedback + cTBS to somatosensory cortex Experimental Treatment 2 Interventions

Participants will perform learning tasks while receiving altered auditory feedback.This procedure will be repeated on day 2. cTBS will be applied to the left hemisphere somatosensory cortex following learning. Participants then leave the laboratory and return 24 hours later to assess retention of learning.

Group VI: Altered auditory feedback + cTBS to motor cortex control zone Experimental Treatment 2 Interventions

Participants in a control condition will undergo the same procedures using cTBS to a motor cortex control zone in the right hemisphere (associated with the hand muscle first dorsal interosseous). cTBS will be applied following learning and subjects will return 24 hours later to test for retention. This control condition is included as a test for non-specific effects of cTBS stimulation.

Group VII: Altered auditory feedback + cTBS to motor cortex Experimental Treatment 2 Interventions

Participants will perform learning tasks while receiving altered auditory feedback.This procedure will be repeated on day 2. cTBS will be applied to the left hemisphere motor cortex following learning. Participants then leave the laboratory and return 24 hours later to assess retention of learning.

Group VIII: Altered auditory feedback + cTBS to auditory cortex Experimental Treatment 2 Interventions

Participants will perform learning tasks while receiving altered auditory feedback.This procedure will be repeated on day 2. cTBS will be applied to the left hemisphere auditory cortex following learning. Participants then leave the laboratory and return 24 hours later to assess retention of learning.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

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]

Continuous theta burst stimulation (cTBS) can effectively induce temporary impairments in semantic processing, similar to traditional 1 Hz repetitive transcranial magnetic stimulation (rTMS), as shown in a study with 80 subjects across five groups.

cTBS at 90% active motor threshold resulted in a significant increase in reaction times during a lexical decision task, indicating its efficacy in creating 'virtual lesions' in the left superior temporal cortex, while also being faster and more comfortable for participants compared to 1 Hz rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the after-effects of continuous theta burst stimulation and conventional 1 Hz rTMS on semantic processing. Brückner, S., Kiefer, M., Kammer, T.[2013]

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]

Theta-burst stimulation (TBS) was found to be safe for children, with no serious adverse events reported among 40 participants aged under 18, including those with Tourette syndrome and typically developing children.

Only 11.6% of participants experienced mild, self-limited side effects, such as finger twitching and headaches, indicating that TBS is well tolerated in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. Wu, SW., Shahana, N., Huddleston, DA., et al.[2012]

The study demonstrated that electrical theta burst stimulation (eTBS) can be safely applied to the primary motor cortex at intensities up to 10 mA, with only mild side effects reported by a few participants.

Despite the safe application of eTBS, none of the tested protocols produced lasting effects on muscle-evoked potential (MEP) amplitudes compared to sham stimulation, indicating that further research is needed to optimize stimulation parameters for efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5 kHz Transcranial Alternating Current Stimulation: Lack of Cortical Excitability Changes When Grouped in a Theta Burst Pattern. Kunz, P., Antal, A., Hewitt, M., 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]

The study found that continuous theta-burst stimulation (cTBS) can effectively reduce cortical excitability, but its effects show limited reproducibility across sessions, indicating variability in its impact.

Among the neurophysiological markers assessed, the modulation of corticospinal excitability measured 5 minutes after cTBS was the most consistent, suggesting it could be a reliable measure for future research on cTBS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants. Vernet, M., Bashir, S., Yoo, WK., et al.[2022]

In a study involving 16 young participants, inhibition of the right Broca homolog using continuous theta burst stimulation (cTBS) did not show a significant effect on new word learning performance at the group level.

However, the effectiveness of cTBS on learning was influenced by individual differences, particularly the level of resting-state alpha-band coherence in the brain, suggesting that the impact of rTMS may vary based on each person's unique neural network state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurobiological Correlates of Inhibition of the Right Broca Homolog during New-Word Learning. Nicolo, P., Fargier, R., Laganaro, M., et al.[2022]

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]

Paired associative stimulation (PAS) significantly increased motor evoked potential (MEP) amplitudes in the primary motor cortex, indicating enhanced cortical excitability, while intermittent theta burst stimulation (iTBS) did not produce significant changes.

The study involved 16 healthy young participants and demonstrated that PAS is a robust method for inducing excitatory changes in the motor cortex, making it a valuable tool for investigating brain plasticity in both healthy individuals and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paired associative stimulation increases motor cortex excitability more effectively than theta-burst stimulation. Player, MJ., Taylor, JL., Alonzo, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10465698/

Continuous theta burst stimulation over right cerebellum for ... The primary outcome measures are voice/speech quality and neurobehavioral parameters of auditory-vocal integration. The secondary outcome measures are cognitive ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X12001970

Hearing Safety of Long-Term Treatment with Theta Burst ... Theta burst stimulation of the temporal and temporoparietal cortex appears to be safe with respect to hearing and speech perception. These data provide evidence ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12340521/

Advances in theta-burst transcranial magnetic stimulation for ... The results showed that the cTBS group showed significantly greater improvement in auditory comprehension and aphasia after 3 weeks of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04818268

NCT04818268 | Sensory Memory in Speech Motor Learning The proposed studies focus on memory for speech movements and sounds and its relation to learning. Continuous theta-burst transcranial magnetic stimulation ( ...

5. frontiersin.org frontiersin.org/journals/integrative-neuroscience/articles/10.3389/fnint.2020.00035/full

Assessing the Effects of Continuous Theta Burst ... We conclude that continuous theta burst stimulation over the dorsolateral prefrontal cortex mainly inhibits cognitive performance.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11366629/

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.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2739195/

Efficacy and safety of bilateral continuous theta burst ... We hypothesize that compared to sham stimulation cTBS can induce a distinctive attenuation of tinnitus distress and loudness and thus be of therapeutic value.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06467292

Speech Motor Learning and Retention (Master Protocol) | ... Continuous theta-burst stimulation (cTBS) is delivered following adaptation to altered auditory feedback to assess its effects on the retention of new learning.