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

Active, not recruiting

Phase N/A Results N/A

Trial Description

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

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.

Conditions

Interventions

  • Transcranial Magnetic Stimulation (Magstim) Device
    ARM 1: Kind: Experimental
    Label: Latency minus 3ms
    Description: 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.
    ARM 2: Kind: Experimental
    Label: Latency minus 5ms
    Description: 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.
    ARM 3: Kind: Experimental
    Label: Latency minus 7ms
    Description: 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.
    ARM 4: Kind: Experimental
    Label: Latency plus 100ms
    Description: 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.

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Subject)
  • Purpose: Basic Science
  • Endpoint: Safety/Efficacy Study
  • Intervention: Crossover Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Change in cortical excitability using single TMS pulses Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application. No

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