Brain Stimulation for Language Disorder

Overseen By Matthew Nelson, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Age less than 18

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

Compensation: Varies

Number of Visits: Unknown

153 Participants Needed

Trial Summary

What is the purpose of this trial?

First, in a recording-only self-paced reading experiment, patients with epilepsy undergoing intracranial monitoring for clinical purposes will read or listen to sentences presented to them one word at time while the investigators simultaneously record neural activity through intracranial electrodes that are implanted for clinical purposes (see subject populations). At the end of the sentence, the subjects have to indicate how they comprehended the sentence by selecting which of several pictures matches the sentence they just read. Behavioral measures that the investigators record and analyze are their response times to advance to each next word in the sentence, and which picture they chose for each sentence. These behavioral measures are compared against the neural activity simultaneously recorded as they are made. Then, in a later session, the same participants will participate in a task-related stimulation experiment. This follows the exact same design as the recording-only reading experiment, the only difference is that on some trials, at controlled moments during the sentence presentation intracranial electrical stimulation is delivered through adjacent intracranial electrode contacts. The investigators will examine the effect of this stimulation on the subjects comprehension of the sentences measured by their behavior, and on the simultaneously recorded neural activity.

Do I have to stop taking my current medications for the trial?

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

What data supports the effectiveness of the treatment Direct brain stimulation, Intracranial Electrical Stimulation, Direct Cortical Stimulation, Sentence Type for language disorders?

Research shows that brain stimulation techniques like transcranial direct current stimulation (tDCS) can enhance speech therapy outcomes in stroke patients, improving language skills such as reading and writing. Additionally, studies indicate that non-invasive brain stimulation can help reorganize brain activity, potentially aiding language recovery after stroke. ^{1 2 3 4 5}

Is brain stimulation for language disorders safe for humans?

Research indicates that brain stimulation techniques, like transcranial direct current stimulation (tDCS), have been safely used in humans for language disorders, with no serious adverse events reported in studies involving stroke survivors with aphasia. ^{6 7 8 9 10}

How does the brain stimulation treatment for language disorder differ from other treatments?

This treatment is unique because it uses brain stimulation, specifically targeting the left lateral prefrontal cortex, to enhance language processing by improving executive-control functions. This approach is different from traditional language therapies as it directly influences brain activity to aid sentence comprehension and production. ^{1 10 11 12 13}

Research Team

Matthew Nelson, MD

Principal Investigator

The University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults over 18 with language disorders who are already undergoing brain monitoring (sEEG or ECoG) for epilepsy. Participants must be able to perform control trials of the task effectively.

Inclusion Criteria

I am currently receiving standard brain monitoring.

I am 18 years old or older.

I can competently perform the required tasks for the study.

Exclusion Criteria

I cannot perform certain tasks accurately on my own.

I am under 18 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Recording-only task

Participants perform language tasks requiring comprehension and response while neural activity is recorded.

1 hour per session

Multiple sessions during hospital stay

Stimulation task

Participants perform language tasks with controlled electrical stimulation to examine effects on comprehension and neural activity.

1 hour per session

Multiple sessions during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Direct brain stimulation
• Sentence Type

Trial Overview The study tests how sentence types and direct brain stimulation affect language comprehension. Patients read or listen to sentences while their neural activity is recorded, then choose pictures matching the sentences. Later, some receive brain stimulation during this task.

Participant Groups

Group I: Intracranial patients Experimental Treatment 2 Interventions

All participants with epilepsy undergoing intracranial monitoring for clinical purposes will be approached to participate in an experiment that is recording-only and an experiment that involves stimulation with simultaneous recording.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

Findings from Research

A 12-week language treatment program for 10 individuals with aphasia improved their ability to process passive sentences, leading to more typical eye movement patterns during sentence comprehension tasks.

Post-treatment, participants showed enhanced predictive processing and thematic analysis for both active and passive sentences, indicating that targeted therapy can effectively support normal-like sentence comprehension processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery of Online Sentence Processing in Aphasia: Eye Movement Changes Resulting From Treatment of Underlying Forms. Mack, JE., Thompson, CK.[2018]

In a study involving two patients with chronic nonfluent aphasia, one patient (G01) showed significant improvement in sentence production and increased activity in Broca's area after treatment, indicating effective engagement of neural substrates for syntax production.

The other patient (J02) did not show similar improvements, suggesting that treatment effects can vary greatly between individuals, potentially due to differences in how their brains utilize existing neural pathways for language tasks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural substrates of syntactic mapping treatment: an fMRI study of two cases. Wierenga, CE., Maher, LM., Moore, AB., et al.[2007]

The combination of dual transcranial direct current stimulation (tDCS) and speech language therapy significantly improved linguistic deficits in a stroke patient with left brain damage, particularly enhancing reading and writing skills.

This approach not only improved specific language tasks, like reading non-words, but also positively affected overall communication quality and other cognitive functions, suggesting a broad therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rehabilitative effects on written language of a combined language and parietal dual-tDCS treatment in a stroke case. De Tommaso, B., Piedimonte, A., Caglio, MM., et al.[2018]

Non-invasive brain stimulation techniques, particularly low-frequency rTMS and cathodal tDCS, can significantly improve naming accuracy in patients with post-stroke aphasia, as shown in a meta-analysis of nine trials with 215 participants, yielding a moderate effect size of 0.51.

The application of these techniques to the non-language dominant hemisphere may promote neural reorganization and reduce competition between brain hemispheres, suggesting a promising adjunct to conventional speech and language therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory non-invasive brain stimulation to homologous language regions as an adjunct to speech and language therapy in post-stroke aphasia: a meta-analysis. Otal, B., Olma, MC., Flöel, A., et al.[2022]

Noninvasive brain stimulation (NIBS), including techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has shown promise in enhancing cognitive functions and inducing adaptive plasticity in both motor and cognitive networks.

Recent advances suggest that combining NIBS with neuroimaging or electrophysiological techniques can effectively modulate neural activity in the language network, which may aid in language recovery for individuals with poststroke aphasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Plasticity in the Healthy Language Network: Implications for Language Recovery after Stroke. Hartwigsen, G.[2018]

Electrical stimulation of cortical and sub-cortical areas of the brain can significantly impact language and speech functions, suggesting a direct relationship between brain activity and verbal abilities.

The study also reviews the effects of surgical procedures, such as resections or coagulations, that follow electrical stimulation, highlighting the potential consequences on verbal communication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of electrostimulation and of resective and stereotactic surgery on language and speech. Lebrun, Y., Leleux, C.[2019]

Transcranial direct current stimulation (tDCS) combined with speech and language treatment (SLT) is safe for stroke survivors with aphasia, showing no serious adverse events during a six-week treatment involving 30 sessions.

Participants receiving active tDCS exhibited greater improvements in functional language compared to those receiving sham treatment, suggesting that tDCS may enhance the effectiveness of SLT, although the superiority of one stimulation polarity over another remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended fMRI-Guided Anodal and Cathodal Transcranial Direct Current Stimulation Targeting Perilesional Areas in Post-Stroke Aphasia: A Pilot Randomized Clinical Trial. Cherney, LR., Babbitt, EM., Wang, X., et al.[2021]

In a study involving 14 patients undergoing left-hemisphere neurosurgery, cortical stimulation mapping revealed nine specific sites in the inferior frontal gyrus that selectively interfered with syntactic encoding during sentence production, without affecting single word processing.

The types of interference observed included errors in grammatical roles and omissions of function words, highlighting the critical role of the left inferior frontal gyrus in constructing syntactic structure in language.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Interference with Syntactic Encoding during Sentence Production by Direct Electrocortical Stimulation of the Inferior Frontal Gyrus. Chang, EF., Kurteff, G., Wilson, SM.[2019]

The study analyzed naming errors in patients undergoing cortical stimulation mapping (CSM) to identify essential language areas, revealing a variety of errors such as semantic paraphasias and phonological paraphasias, which indicate a complex and distributed cortical network involved in language processing.

Using advanced web-based tools, the research mapped the locations of these errors, contributing to our understanding of how different brain regions (frontal, parietal, and temporal) are involved in language comprehension and production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of naming errors during cortical stimulation mapping: implications for models of language representation. Corina, DP., Loudermilk, BC., Detwiler, L., et al.[2021]

In a study involving 6 subjects undergoing awake surgery, stimulation of the inferior frontal gyrus disrupted comprehension of complex passive sentences, highlighting its critical role in syntactic processing.

The results indicate that specific language regions, particularly the pars opercularis, are essential for understanding sentence-level tasks, suggesting that these areas should be targeted in future research on language processing and surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating syntactic comprehension during awake intraoperative cortical stimulation mapping. Riva, M., Wilson, SM., Cai, R., et al.[2023]

In a study involving 12 patients with chronic post-stroke aphasia, anodal transcranial direct current stimulation (tDCS) significantly improved naming abilities after language training compared to sham stimulation, indicating its potential to enhance treatment outcomes.

The benefits of anodal tDCS were maintained for at least 2 weeks post-training, and patients' baseline naming ability was a predictor of how well they responded to the stimulation, suggesting that individual differences may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term anomia training and electrical brain stimulation. Flöel, A., Meinzer, M., Kirstein, R., et al.[2016]

Anodal stimulation of the left lateral prefrontal cortex significantly improved performance in tasks requiring executive control, such as processing ambiguous sentences and complex memory tasks, compared to sham and cathodal stimulation.

This study provides evidence that brain stimulation can effectively reduce cognitive processing demands during language tasks, highlighting the left lateral prefrontal cortex's crucial role in executive control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex. Hussey, EK., Ward, N., Christianson, K., et al.[2020]

A comprehensive analysis of 45 studies identified a network in the brain, primarily in the bilateral frontal and temporal lobes, that is crucial for both understanding and producing sentences.

Differences were noted between auditory and visual sentence comprehension, particularly in the temporal lobes, and complex syntactic sentences engaged additional regions, including the right insula, suggesting that right hemisphere involvement may be important for language recovery in patients with agrammatic aphasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural networks for sentence comprehension and production: An ALE-based meta-analysis of neuroimaging studies. Walenski, M., Europa, E., Caplan, D., et al.[2020]

References

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

Recovery of Online Sentence Processing in Aphasia: Eye Movement Changes Resulting From Treatment of Underlying Forms. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Neural substrates of syntactic mapping treatment: an fMRI study of two cases. [2007]

3. England pubmed.ncbi.nlm.nih.gov

The rehabilitative effects on written language of a combined language and parietal dual-tDCS treatment in a stroke case. [2018]

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

Inhibitory non-invasive brain stimulation to homologous language regions as an adjunct to speech and language therapy in post-stroke aphasia: a meta-analysis. [2022]

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

Adaptive Plasticity in the Healthy Language Network: Implications for Language Recovery after Stroke. [2018]

6. Austria pubmed.ncbi.nlm.nih.gov

The effects of electrostimulation and of resective and stereotactic surgery on language and speech. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Extended fMRI-Guided Anodal and Cathodal Transcranial Direct Current Stimulation Targeting Perilesional Areas in Post-Stroke Aphasia: A Pilot Randomized Clinical Trial. [2021]

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

Selective Interference with Syntactic Encoding during Sentence Production by Direct Electrocortical Stimulation of the Inferior Frontal Gyrus. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Analysis of naming errors during cortical stimulation mapping: implications for models of language representation. [2021]

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

Evaluating syntactic comprehension during awake intraoperative cortical stimulation mapping. [2023]

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

Short-term anomia training and electrical brain stimulation. [2016]

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

Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex. [2020]

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

Neural networks for sentence comprehension and production: An ALE-based meta-analysis of neuroimaging studies. [2020]