Finding an Optimal Latency for Paired Associative Stimulation in People With Chronic Stroke

Study Overview
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Brief Summary
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After a stroke, there is an exaggerated inhibitory influence from the non-stroke hemisphere to the stroke hemisphere. Brain stimulation using repetitive transcranial magnetic stimulation (rTMS) to the non-stroke hemisphere can decrease this inhibition. Paired Associative Stimulation (PAS) may be a more effective way to produce this same inhibition, as shown in healthy subjects. However, it is not known whether this will translate to people with stroke. PAS consists of a peripheral nerve stimulus paired a short time later with a cortical stimulus to change the excitability within the brain. Thus the investigators will apply PAS to people with stroke, but the investigators need to first determine the most effective interpulse interval (IPI) between the peripheral and cortical stimuli. Our research question is which of three different IPIs is most effective in changing the excitability of the brain. The purpose of this study is to determine the optimal IPI between a peripheral nerve pulse and a cortical stimulus that will be most effective in changing excitability of the brain in people with chronic stroke. The investigators hypothesize that the cortical excitability of the nonstroke hemisphere will be most inhibited with the latency-5ms condition.

Detailed Description
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Numerous PAS studies have been done in healthy subjects and all have been done safely. The proper interpulse interval in healthy individuals between the peripheral nerve stimulus and the cortical stimulus is known to be latency-5ms. However, this may be different in individuals with stroke. Specific Aim: what is the optimal interpulse interval to achieve the maximum inhibitory effect in the nonstroke hemisphere? We will recruit three subjects with chronic stroke. Electroencephalography (EEG) will be used to determine the latency between the peripheral nerve stimulus and the sensory evoked potential in each subject. We will then assess the following IPIs on each subject in a random order: latency - 3ms, -5ms and -7ms. There will be a fourth condition of latency + 100ms (known to have no effect) to be used as a control. The washout period will be at least one week between each of these conditions. The optimal IPI will be determined from these tests by comparing single pulse transcranial magnetic stimulation (TMS) measures for cortical excitability. Prior to each treatment, each subject will receive 20 single pulse cortical stimuli to serve as pretest data. The post tests for each condition will consist of 20 single pulse cortical stimuli at 0, 5, 10, 15, 30, 45 and 60 minutes after the PAS condition. Data analysis will consist of a single-subject analysis with the two standard deviation bandwidth method of each post-test compared to pre-test. We hypothesize that there will be no adverse advents and that this optimal IPI will be latency-5ms.

Official Title
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Effect of Different Interpulse Intervals of Paired Associative Stimulation on Cortical Excitability in People With Chronic Stroke

Conditions
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Stroke

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation (Magstim)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stroke (ischemic or hemorrhagic) of greater than 6 months duration impairment in the paretic hand over 18 years old male or female on mini mental status exam must have score of 22 or higher must have elicitable motor evoked potential (MEP) Exclusion Criteria: seizure within the past two years receptive aphasia epileptogenic medication major psychiatric disorder other interfering comorbidities pregnancy

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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Latency minus 3ms<br>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (Latency - 3ms) where latency refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. | Device: Transcranial Magnetic Stimulation (Magstim)<br> <br> * Other names: Magstim;|
| Experimental: Latency minus 5ms<br>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (Latency - 5ms) where latency refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. | Device: Transcranial Magnetic Stimulation (Magstim)<br> <br> * Other names: Magstim;|
| Experimental: Latency minus 7ms<br>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (Latency - 7ms) where latency refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. | Device: Transcranial Magnetic Stimulation (Magstim)<br> <br> * Other names: Magstim;|
| Active Comparator: Latency plus 100ms<br>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (Latency + 100ms), known to have no effect, where latency refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. | Device: Transcranial Magnetic Stimulation (Magstim)<br> <br> * Other names: Magstim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cortical excitability using single TMS pulses | Assess average size of 20 motor evoked potentials via electromyography (EMG) signal resulting from single TMS pulses to the motor cortex. Measurements taken before and after paired associative stimulation treatment at each session. | Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAS, TMS, Stroke, Paired Associative Stimulation, Transcranial Magnetic Stimulation