The purpose of this study is to identify and establish how the area of the brain that controls motor function (motor cortex) of the non-affected hemisphere after stroke might serve as a new target for therapeutic interventions to improve motor performance after stroke.
It is well known that the motor area of one hemisphere of the brain (motor cortex) controls the movement of the opposite side of the body but the role of the motor cortex in the hemisphere spared by stroke (contralesional motor cortex) in motor performance during post stroke recovery is still unclear. It is also not clear whether the motor cortex of both hemispheres of the brain are involved, as movement becomes more complicated. Currently the role of the motor cortex on the same side of the body (referred to as ipsilateral motor cortex) in hand performance remains controversial. In most patients with stroke, only one side of the brain is affected by the stroke (affected hemisphere) resulting in weakness of half of the body opposite to the side of the stroke. Over the recent years, research has discovered that the side of the brain, that is spared by the stroke (non-affected hemisphere) may support recovery after stroke. However, there is also a question whether the non-affected hemisphere may interfere with the process of recovery. It is currently not known what factors influence the activity of non-affected hemisphere to either support or interfere with the recovery of stroke. A better understanding of those events is critical to development of optimal therapeutic strategies. For example, non-invasive stimulation of specific areas of the non-affected hemisphere may help to improve functional recovery following stroke. The objectives of this study are to define the factors that influence the activity in the non-affected hemisphere to either support or interfere with the recovery after stroke. The researchers will study the area of the brain that controls movements of the non-affected hemisphere as it relates to motor function post-stroke. Transcranial magnetic stimulation (TMS) is a device that allows non-invasive stimulation of the brain. When the brain is stimulated repetitively at a very low rate and low intensity for about 15 minutes, the stimulated brain area becomes less active. This effect lasts 10 minutes and is called a "transient artificial lesion" as it mimics the effects of transiently interfering with the function of the stimulated brain area. The study includes experiments that first identify the extent of stroke and brain areas involved in a motor task using functional MRI of the brain and TMS. The researchers will then determine the functional role of the contralesional motor cortex by studying the effect of low frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) on interhemispheric inhibition (IHI) (resting and active) and motor cortex excitability (short interval intracortical excitability and corticospinal excitability) and behavior. The researchers will thereby also identify rTMS protocols that enhance motor performance in stroke patients. In this study the researchers will conduct experiments using repetitive TMS to downregulate the activity of the motor area and measures its effect on activity of motor cortex of both hemispheres. In addition to enrolling participants who have had a stroke, the researchers will enroll healthy participants as this collected data will provide normative values for task related changes in M1s and their interactions - a prerequisite to studying abnormalities in stroke patients during motor recovery. The measurements and interventions will occur at two time points in all participants with stroke (1 and 6 months post-stroke). The data will be compared to the results of healthy age matched controls, assessed at a single time point.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
100
Single-pulse Transcranial Magnetic Stimulation (TMS) is a brief magnetic pulse that is applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Single-pulse transcranial magnetic stimulation (TMS) will be administered at study visits.
Paired-pulse Transcranial Magnetic Stimulation (ppTMS) is two brief sequential magnetic pulses that are applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Paired-pulse transcranial magnetic stimulation (ppTMS) will be administered at study visits.
Center for Rehabilitation Medicine
Atlanta, Georgia, United States
Emory University Hospital
Atlanta, Georgia, United States
Emory University School of Medicine
Atlanta, Georgia, United States
Motor Function Assessed by the Jebsen Test
The Jebsen Test assesses weighted and non-weighted hand function among participants who have had a stroke. Subjects are assessed through writing, turning over 3 by 5 inch cards, picking up small common objects, simulated feeding, stacking checkers, picking up large objects, and picking up large heavy objects. Patients are required to perform all of the subtests with both the right and left hands. Time to complete each task is recorded and normalized to healthy age and sex matched control subjects. The score ranges from 0 to 1 with 0 being normal.
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Mean Motor Evoked Potential (MEP) Amplitudes Assessed by Stimulus Response Curve (SRC) of the Contralesional M1
Change in mean motor evoked potential (MEP) amplitudes at each stimulus intensity will be calculated. The sum of these means is calculated as the area under the curve.
Time frame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Presence of MEP in Response to TMS of the Ipsilesional M1
The presence of motor evoked potential (MEP) in response to maximum TMS applied to ipsilesional M1 was determined in participants with stroke.
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Lesion Volume
Normalized stroke lesion volume was determined at the one-month time point using structural MRI of the brain.
Time frame: 1 month post-stroke (subacute stroke)
Corticospinal Tract (CST) Lesion
Corticospinal tract (CST) lesion load will be determined at the one-month time point using structural MRI of the brain. The lesion size is expressed as percentage of the entire CST.
Time frame: 1 month post-stroke (subacute stroke)
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Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) is a sequence of brief magnetic pulses that are applied at 0.1 Hz frequency at low intensity through an air-cooled coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Low-frequency repetitive transcranial magnetic stimulation (rTMS) will be administered at study visits.
Sham motor cortex stimulation will be applied at study visits.
Motor Function Assessed by Time to Complete the Wolf Motor Function Test (WMFT)
Upper extremity motor ability among participants who had a stroke was evaluated with the Wolf Motor Function Test (WMFT). The test consists of 17 items (6 joint-segment movements, 9 integrative functional movements and 2 strength items). The items are rated on a 6-point functional ability scale (FAS) where 0 is "no attempt is made to use the more affected arm and 5 is a normal appearance of movement execution. The time taken to complete each task will be recorded up to 120 seconds. The mean time to complete all tasks will be used to evaluate motor ability.
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Motor Function Assessed by Grip Strength During the Wolf Motor Function Test (WMFT)
During the grip strength assessment of the WMFT, participants grip a dynamometer with as much strength as possible. There are three trials of gripping with a minute rest interval between trials. The mean kilograms of strength exerted during the three trials is calculated.
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Use of Paretic Arm Assessed by the Motor Activity Log (MAL)
In stroke patients, the everyday use of the paretic (the more affected) arm will be measured using the Motor Activity Log (MAL). The MAL is a subjective measure of semi- structured interview to examine a) how much and b) how well the subject uses their more-affected arm outside of the laboratory setting. Total scores range from 0 (no use of the more-affected arm) to 5 (use is as good as before stroke).
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
CST Subpathway Originating in M1 Lesion Load
CST sub M1 lesion volume will be determined at the one- month time point using structural MRI of the brain. The lesion load is expressed as percentage of the entire CST.
Time frame: 1 month post-stroke (subacute stroke)
Primary Motor Cortex (M1) Activity, Assessed by Functional Magnetic Resonance Imaging (fMRI)
Functional Magnetic Resonance Imaging (fMRI) will be used to determine hand movement related activity in the motor cortex of the brain in all subjects. Blood oxygenation level dependent (BOLD) response during execution of the motor task will be compared to rest. The subacute stroke and chronic stroke time points are compared to single study visit of healthy controls.
Time frame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Short Interval Cortical Inhibition (SICI) Measured by Repeated Transcranial Magnetic Stimulation (rTMS)
SICI in the contralesional M1 will be measured using paired pulse TMS at an interstimulus interval (ISI) of 2 milliseconds (ms). Cortical stimulation intensity was delivered at 60% and 80% of the motor threshold (MT). SICI is expressed as the ratio between the mean MEP amplitude in response to a single TMS and the mean MEP amplitude in response to a paired pulse TMS. A ratio of 1 means no inhibition, a ratio smaller than 1 means inhibition, and a ratio greater than 1 means facilitation.
Time frame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Peak Velocity During Wrist Extension Movement
Stroke patients are asked to rapidly execute 7 ballistic wrist extension movements following an auditory cue. A 2-dimensional gyrometer is mounted on the dorsum of the hand to measure wrist extension movements. Electromyography (EMG) activity will be recorded on the extensor carpi ulnaris (ECU) muscle, a muscle that supports wrist extension movements.
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)