Brain State-dependent PCMS in Chronic Stroke

Study Overview
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Brief Summary
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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.

Official Title
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Upregulating Corticospinal Function After Stroke Using Brain State-dependent Paired Corticomotoneuronal Stimulation

Conditions
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Stroke

Intervention / Treatment
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* Combination Product: Brain state-dependent paired corticomotoneuronal stimulation (PCMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of stroke > 6 months ago Presence of residual upper extremity hemiparesis Willingness to participate Ability to provide informed consent Upper extremity Fugl-Meyer score < 66 Mini Mental State Exam score > 24 Discernible and reliable motor-evoked potential (MEP) elicited following single-pulse TMS to the lesioned hemisphere Exclusion Criteria: History of neurological disease other than stroke Presence of contraindications to transcranial magnetic stimulation (TMS) or peripheral nerve stimulation (PNS), including: history of adverse reactions to TMS or PNS metal in head, eyes, neck, chest/trunk, or arms, including but not limited to shrapnel, surgical clips, fragments from metalworking, fragments from welding, implanted device, history of frequent and severe headaches or migraines, immediate family history of seizure or epilepsy, personal history of seizure or epilepsy, current, suspected, or planned pregnancy, current or recent (within the last 3 months) use of medications acting on the central nervous system other than selective serotonin reuptake inhibitors (SSRIs), including but not limited to antipsychotic drugs, benzodiazepines, prescription stimulants. Upper extremity Fugl-Meyer score ≥ 66 (66 is the maximum on this scale) Mini Mental State Exam score <= 24 No discernible and reliable MEP elicited following single-pulse TMS to the lesioned hemisphere

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCMS during brain states reflecting strong corticospinal transmission<br> | Combination Product: Brain state-dependent paired corticomotoneuronal stimulation (PCMS)<br>* Paired corticomotoneuronal stimulation (PCMS) involves delivering precisely timed pairs of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) so that the neuronal activity evoked by such stimulation arrives synchronously at corticospinal-motoneuronal synapses. This synchronous arrival is postulated to cause long-term potentiation via spike timing-dependent plasticity, which then improves corticospinal transmission and hand function. In this study, paired corticomotoneuronal stimulation (PCMS) will be applied during specific brain states that reflect increased recruitment of motoneurons via the corticospinal tract. This increased recruitment is expected to enhance the beneficial effects of PCMS on human hand function after stroke.<br>|
| Active Comparator: PCMS during random brain states<br> | Combination Product: Brain state-dependent paired corticomotoneuronal stimulation (PCMS)<br>* Paired corticomotoneuronal stimulation (PCMS) involves delivering precisely timed pairs of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) so that the neuronal activity evoked by such stimulation arrives synchronously at corticospinal-motoneuronal synapses. This synchronous arrival is postulated to cause long-term potentiation via spike timing-dependent plasticity, which then improves corticospinal transmission and hand function. In this study, paired corticomotoneuronal stimulation (PCMS) will be applied during specific brain states that reflect increased recruitment of motoneurons via the corticospinal tract. This increased recruitment is expected to enhance the beneficial effects of PCMS on human hand function after stroke.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum hand force output | This will be measured using maximum voluntary contractions of the stroke-affected first dorsal interosseous hand muscle during pinching actions. | up to 1 hour after intervention | 
| Maximum hand muscle activation | This will be measured using electromyography recordings of the stroke-affected first dorsal interosseous muscle during maximum voluntary contractions during pinching actions | up to 1 hour after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amplitude of motor evoked potentials | This will be measured as the peak-to-peak amplitude of motor-evoked potentials recorded from the stroke-affected first dorsal interosseous muscle | up to 1 hour after intervention | 
| Time to complete the 9-hole peg test | This will be measured as the time needed to complete the task using the stroke-affected hand. | up to 1 hour after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic, movement