Brain Stimulation for Speech Motor Learning

Recruiting at 1 trial location

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

Trial Summary

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 data supports the effectiveness of the treatment Adaptation, cTBS, Continuous Theta-Burst Stimulation, cTBS, Theta-Burst Transcranial Magnetic Stimulation for speech motor learning?

Research shows that continuous theta burst stimulation (cTBS) can influence brain activity related to motor learning, which might help in speech motor learning. Studies have found that cTBS can affect motor cortex excitability and motor learning, suggesting it could be useful for improving speech-related motor skills. ^{1 2 3 4 5}

Is theta-burst transcranial magnetic stimulation (TBS) safe for humans?

Theta-burst transcranial magnetic stimulation (TBS) is generally considered safe for humans, with most adverse events being mild and occurring in about 5% of people. However, there is a small risk of seizures, so it should be used with caution, especially since it is a relatively new technique. ^{2 4 6 7 8}

How is the treatment cTBS different from other treatments for speech motor learning?

Continuous theta-burst stimulation (cTBS) is unique because it uses magnetic pulses to temporarily reduce brain activity in specific areas, which can help with learning speech motor skills by targeting the brain's motor cortex. Unlike other treatments, cTBS can produce longer-lasting effects with a brief session, making it a novel approach for enhancing speech motor learning. ^{1 3 4 6 9}

What is the purpose of this trial?

The proposed studies focus on memory for speech movements and sounds and its relation to learning. Continuous theta-burst transcranial magnetic stimulation (cTBS) will be used to suppress activity in a region of pre-frontal cortex associated with somatic and auditory working memory (Brodmann area 46v) to test its involvement in learning.

Research Team

David Ostry

Principal Investigator

Haskins Laboratories

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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) 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. [2018]

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

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

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

Paired associative stimulation increases motor cortex excitability more effectively than theta-burst stimulation. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Prolonged motor skill learning--a combined behavioural training and θ burst TMS study. [2013]

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

Comparing the after-effects of continuous theta burst stimulation and conventional 1 Hz rTMS on semantic processing. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. [2012]

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

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Discrimination of speech and non-speech sounds following theta-burst stimulation of the motor cortex. [2022]