Stroke
Conditions
Keywords
PAS, TMS, Stroke, Paired Associative Stimulation, Transcranial Magnetic Stimulation
Brief summary
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.
Interventions
DEVICETranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (Latency - 3ms)
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.
DEVICETranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (Latency - 5ms)
Transcranial Magnetic Stimulation 5ms
DEVICEranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (Latency - 7ms)
Transcranial Magnetic Stimulation 7ms
DEVICETranscranial Magnetic Stimulation Time 100ms
Active Compator
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DEVICE_FEASIBILITY
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
Countries
United States
Participant flow
Pre-assignment details
There were no significant events or excluded participants prior to being assigned an intervention order
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants This is a cross-over study; all participants completed all four treatment arms. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 4 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 2 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
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.
Time frame: Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Latency Minus 3ms | Change in Cortical Excitability Using Single TMS Pulses | -.07667 Log10(microvolts) | Standard Deviation 0.06184 |
| Latency Minus 5ms | Change in Cortical Excitability Using Single TMS Pulses | 0.11 Log10(microvolts) | Standard Deviation 0.06164 |
| Latency Minus 7ms | Change in Cortical Excitability Using Single TMS Pulses | -.05667 Log10(microvolts) | Standard Deviation 0.2625 |
| Latency Plus 100ms | Change in Cortical Excitability Using Single TMS Pulses | .1233 Log10(microvolts) | Standard Deviation 0.15173 |