Brain State-Dependent PCMS for Stroke Recovery

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Texas at Austin

Must not be taking: Antipsychotics, Benzodiazepines, Stimulants, others

Disqualifiers: Neurological disease, Metal in body, others

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

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

After stroke, people often have difficulty using their hands. Combined brain and nerve stimulation can strengthen the neural pathways that control hand function. In this study, we will deliver combined brain and nerve stimulation during specific time windows that increase activation of neural pathways underlying hand function. We will compare the effects of combined brain and nerve stimulation during these optimal time windows to the effects of combined brain and nerve stimulation applied during random time windows on post-stroke hand function.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that act on the central nervous system, except for selective serotonin reuptake inhibitors (SSRIs), at least 3 months before participating.

Is Brain State-Dependent PCMS safe for humans?

The research on Brain State-Dependent PCMS, also known as Paired Corticomotoneuronal Stimulation, suggests it is generally safe for humans. Studies have shown it can increase the excitability of pathways in the brain without significant adverse effects, although it remains experimental and should be conducted within scientific studies. ^{1 2 3 4 5}

How is the Brain State-Dependent PCMS treatment different from other stroke recovery treatments?

Brain State-Dependent PCMS is unique because it uses brain activity to guide stimulation, making it more personalized and potentially more effective than traditional methods. This approach, known as activity-dependent stimulation, aims to strengthen brain connections by responding to specific brain signals, unlike standard treatments that do not adapt to individual brain states. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Brain State-dependent Paired Corticomotoneuronal Stimulation (PCMS) for stroke recovery?

Research shows that activity-dependent stimulation, which is similar to Brain State-dependent PCMS, can enhance recovery by strengthening brain connections. Studies on similar techniques, like repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have shown promise in improving motor function after stroke by enhancing brain plasticity (the brain's ability to adapt and reorganize). ^{6 8 9 11 12}

Eligibility Criteria

This trial is for individuals who have had a stroke at least 6 months ago and now struggle with hand function due to upper extremity hemiparesis. They must be mentally fit (with a Mini Mental State Exam score over 24), willing to participate, able to consent, and have some movement in their affected arm but not full recovery (Fugl-Meyer score under 66).

Inclusion Criteria

I had a stroke more than 6 months ago.

You scored higher than 24 on the Mini Mental State Exam.

I have weakness in one of my arms.

Exclusion Criteria

Your score on a mental exam is 24 or lower.

You have medical reasons that make it unsafe for you to receive transcranial magnetic stimulation or peripheral nerve stimulation.

My brain does not respond normally to a specific type of brain scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combined brain and nerve stimulation during specific time windows to enhance hand function

4 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Brain State-dependent Paired Corticomotoneuronal Stimulation (PCMS)
• Phase-dependent Paired Corticomotoneuronal Stimulation (PCMS)

Trial Overview The study tests whether delivering paired corticomotoneuronal stimulation (PCMS) during specific brain states improves hand function after stroke compared to random timing of PCMS. It aims to strengthen the neural pathways that control the hand by using combined brain and nerve stimulation.

Participant Groups

Group I: PCMS during brain states reflecting strong corticospinal transmission Experimental Treatment 1 Intervention

Group II: PCMS during random brain states Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Findings from Research

The TMS Synchronized Exoskeleton Feedback (TSEF) platform, which combines real-time feedback from exoskeleton movements and brain stimulation, showed promising results in enhancing cortical excitability in stroke patients, with a significant increase in Motor Evoked Potential and improvement in clinical scales after 20 sessions.

In a proof-of-concept study involving three patients, the TSEF platform demonstrated clinical gains that were not observed in a control group receiving standard physiotherapy, suggesting that personalized brain stimulation may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized closed-loop TMS synchronized with exoskeleton for modulation of cortical-excitability in patients with stroke: a proof-of-concept study. Singh, N., Saini, M., Kumar, N., et al.[2023]

New brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex of stroke patients, potentially improving motor function.

Activity-dependent stimulation, which tailors brain stimulation to the patient's neural or muscular activity, may offer even better outcomes compared to traditional neurorehabilitation methods, suggesting a promising direction for future stroke rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New modalities of brain stimulation for stroke rehabilitation. Edwardson, MA., Lucas, TH., Carey, JR., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

The impact of closed-loop intracortical stimulation on neural activity in brain-injured, anesthetized animals. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Individualized closed-loop TMS synchronized with exoskeleton for modulation of cortical-excitability in patients with stroke: a proof-of-concept study. [2023]

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

Safety of 6-Hz primed low-frequency rTMS in stroke. [2015]

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

Cortical stimulation as an adjuvant to upper limb rehabilitation after stroke. [2016]

5. Germany pubmed.ncbi.nlm.nih.gov

New modalities of brain stimulation for stroke rehabilitation. [2021]

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

Restoration of intracortical and thalamocortical circuits after transplantation of bone marrow mesenchymal stem cells into the ischemic brain of mice. [2021]

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

Involvement of N-methyl-d-aspartate receptors in plasticity induced by paired corticospinal-motoneuronal stimulation in humans. [2019]

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

Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation. [2020]

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

High-intensity, low-frequency repetitive transcranial magnetic stimulation enhances excitability of the human corticospinal pathway. [2021]

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

Controversy: Noninvasive and invasive cortical stimulation show efficacy in treating stroke patients. [2022]

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

Cortical propagation tracks functional recovery after stroke. [2021]

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

Cortical Excitability Measured with nTMS and MEG during Stroke Recovery. [2018]