Brain Stimulation for Speech Motor Learning

Recruiting at 2 trial locations

Overseen By David Ostry

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Antipsychotics, Antidepressants, Antianxiety

Disqualifiers: Epilepsy, Concussion, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Single day

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a brain stimulation technique called cTBS (Continuous Theta-Burst Stimulation) to aid in learning speech movements and sounds. Researchers aim to determine if this technique can alter the brain's memory areas during speech hearing or production. The trial includes several groups, with some receiving cTBS and others concentrating on memory tasks. Right-handed adults without neurological issues are ideal candidates. As an unphased trial, participants can contribute to groundbreaking research in speech and memory.

Will I have to stop taking my current medications?

Yes, you will need to stop taking antipsychotic, antidepressant, and antianxiety drugs to participate in this trial.

What prior data suggests that continuous theta-burst transcranial magnetic stimulation (cTBS) is safe for speech motor learning?

In a previous study, researchers tested a technique called continuous theta-burst transcranial magnetic stimulation (cTBS) on over 1,000 people, including both healthy individuals and those with conditions like autism. The results showed that cTBS is generally safe and well-tolerated. Most participants experienced minor side effects, such as headaches or scalp discomfort, which resolved quickly.

Research has also shown that adapting to altered auditory feedback, a method used to study speech and hearing, is safe. Studies have found that people can adjust to changes in the sounds they hear while speaking without any major safety issues.

Both cTBS and altered auditory feedback have been studied separately and found to be safe. This indicates that the treatments in this trial have a strong safety record in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the brain stimulation technique called cTBS, or continuous theta-burst stimulation, for speech motor learning because it offers a novel approach to enhancing speech abilities. Unlike traditional speech therapy, which primarily relies on practice and repetition, cTBS targets specific brain regions to potentially accelerate motor learning and adaptation. This technique could lead to faster and more effective improvements in speech by directly influencing the brain's plasticity, making it a promising avenue for treating speech-related issues.

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

Research has shown that continuous theta-burst stimulation (cTBS) can improve language skills in individuals with language difficulties, such as aphasia. Studies have found that cTBS enhances the understanding of spoken words and aids in language recovery. In this trial, some participants will receive cTBS combined with adaptation to altered auditory feedback or sensory memory tasks. For those adjusting to changes in how they hear their own voice, research indicates that individuals can modify their speech in response, potentially improving their speech learning. Additionally, sensory memory, which involves the brain's ability to remember sensory experiences, plays a crucial role in learning to speak. It helps individuals remember and adjust their speech based on sensory input. ^{6 7 8 9 10}

Who Is on the Research Team?

David Ostry

Principal Investigator

Haskins Laboratories

Are You a Good Fit for This Trial?

This trial is for right-handed adults with no known physical or neurological abnormalities. It's not suitable for those with metal in their body, claustrophobia, on antipsychotic/antidepressant/antianxiety drugs, pregnant women, anyone with heart clips or implants, a history of concussion or epilepsy.

Inclusion Criteria

I do not have any known physical or neurological abnormalities.

I am right-handed.

Exclusion Criteria

You or a family member have a history of epilepsy.

metal or metallic fragments in any part of the body

I am currently on medication for anxiety.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo auditory and somatosensory working memory tests followed by adaptation to altered auditory feedback. cTBS is used to disrupt neural activity in Brodmann area 46v.

Single day

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adaptation
• cTBS

Trial Overview The study tests how suppressing activity in part of the brain (Brodmann area 46v) using cTBS affects learning speech movements and sounds. The focus is on understanding memory's role in speech motor learning.

How Is the Trial Designed?

Group I: Somatosensory Sensory Memory Experimental Treatment 1 Intervention

Somatosensory Sensory Memory

Group II: Sensory Memory + cTBS to 46v Experimental Treatment 2 Interventions

Sensory Memory + cTBS to 46v

Group III: Auditory Sensory Memory Experimental Treatment 1 Intervention

Auditory Sensory Memory

Group IV: Adaptation to Altered Auditory Feedback + cTBS to 46v Experimental Treatment 2 Interventions

Adaptation to Altered Auditory Feedback + cTBS to 46v

Group V: Adaptation to Altered Auditory Feedback Experimental Treatment 1 Intervention

Adaptation to Altered Auditory Feedback

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?

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) over the lip motor representation impairs the ability to discriminate between lip-articulated speech sounds, such as 'ba' and 'da', indicating a specific role of the motor cortex in processing these sounds.

No changes in motor excitability were observed after cTBS, suggesting that the effects on speech discrimination are not due to changes in motor excitability but rather reflect the importance of articulatory features in speech perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discrimination of speech and non-speech sounds following theta-burst stimulation of the motor cortex. Rogers, JC., Möttönen, R., Boyles, R., 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]

In a study involving 30 healthy participants, inhibitory continuous theta burst stimulation (cTBS) decreased motor cortex excitability and slowed motor learning, while excitatory intermittent theta burst stimulation (iTBS) increased excitability but did not enhance learning performance.

The findings suggest that the effects of TBS on motor learning are more related to changes in motor cortex plasticity rather than just the level of activation, which could inform future neurorehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Jelić, MB., Milanović, SD., Filipović, SR.[2018]

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]

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]

Prolonged motor practice over three weeks led to significant improvements in motor skills for the non-dominant arm, with similar benefits observed in the dominant arm, indicating enhanced overall sensorimotor abilities.

Inhibiting motor-related brain regions with continuous theta burst stimulation (cTBS) after extensive training did not harm motor performance; in fact, cTBS applied to the primary motor cortex (M1) even improved performance in certain tasks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged motor skill learning--a combined behavioural training and θ burst TMS study. Platz, T., Roschka, S., Doppl, K., et al.[2013]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4433313/

Auditory-Perceptual Learning Improves Speech Motor ... In the present study, the 5–7-year-old children were capable of adapting to the altered auditory feedback even prior to perceptual training, indicating that ...

2. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2018.00091/full

Online Adaptation to Altered Auditory Feedback Is ... We conclude that adaptation to altered auditory feedback is very well-predicted by general auditory acuity, as suggested by the DIVA model. In line with the ...

3. nature.com nature.com/articles/s44271-025-00304-8

Auditory-motor adaptation and de-adaptation for speech ... Auditory-motor adaptation and de-adaptation for speech depend more on time in the new environment than on the amount of practice | ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5857594/

Online Adaptation to Altered Auditory Feedback Is ... We conclude that adaptation to altered auditory feedback is very well-predicted by general auditory acuity, as suggested by the DIVA model. In line with the ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304394015001160

Feedback delays eliminate auditory-motor learning in ... We investigated adaptation to altered auditory feedback during speech articulation. •. Speech audio-motor adaptation is completely eliminated with delays of 100 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8259784/

Speech auditory-motor adaptation to formant-shifted feedback ... Auditory-motor adaptation to frequency-altered auditory feedback occurs when participants ignore feedback. BMC Neuroscience, 14, 25. 10.1186/1471-2202-14-25 ...

7. pubs.asha.org pubs.asha.org/doi/abs/10.1044/2025_PERSP-24-00306?af=R

Can Typically Fluent Adults Adapt to Long-Latency ... Speech auditory–motor adaptation to formant-shifted feedback lacks an explicit component: Reduced adaptation in adults who stutter reflects limitations in ...

8. elifesciences.org elifesciences.org/articles/73694

A single exposure to altered auditory feedback causes ... The paper establishes the presence of a single-trial adaptation response to the perturbation of the first formant of a vowel in speech production.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8642089/

Auditory Feedback Is Used for Adaptation and ... The aim of this study was to examine adaptation in response to temporal perturbation using real-time perturbation of ongoing speech.

10. bmcneurosci.biomedcentral.com bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-14-25

Auditory-motor adaptation to frequency ... - BMC Neuroscience These data suggest that musical training is effective in suppressing compensatory responses only when FAF occurs after vocal onset (500-2500 ms).