Stroke
Conditions
Keywords
Transcranial Magnetic Stimulation, Hemiparesis, Post-stroke rehabilitation
Brief summary
The goal of the study is to determine the effect of repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex on training-related improvements in motor performance and associated neural plasticity.
Detailed description
Occlusion of the middle cerebral artery is the most common cause of stroke. Because the middle cerebral artery supplies blood to the motor cortices, middle cerebral artery stroke often impacts the integrity of the motor cortex and its associated corticospinal projections. Consequently, the majority of the 6.8 million people who have suffered a stroke in the United States experience hemiparesis as a result of the infarct. Although stroke survivors are encouraged to participate in rehabilitation programs, less than half of all individuals post-stroke regain complete motor function. Because motor deficits, especially of the upper extremities, can dampen the quality of life, there is an urgent need to improve current rehabilitation programs to allow more stroke survivors to achieve higher functional gains. Motor training is an important part of recovery after stroke. During motor training, stroke patients practice performing a movement and become better at performing the trained movement over time. Repetitive transcranial magnetic stimulation (rTMS), which uses magnetism to excite neurons near the surface of the brain, may further improve performance. Healthy adults made larger training-related improvements in their motor performance when they received rTMS over the primary motor cortex during motor training. There is evidence that the premotor cortex may be a more effective target than the primary motor cortex for rTMS for some stroke survivors. In the current study, the investigator will determine the effect of rTMS over the premotor cortex on training-related improvements in motor performance in healthy adults. In this study the researchers will evaluate the effect of premotor cortex (PMC) rTMS on motor learning with a double-blind randomized study consisting of five experiments separated by at least 72 hours. During each experiment, participants complete motor training while receiving one of five rTMS protocols. All participants will receive each rTMS protocol once. The order of the rTMS protocols will be randomized and counterbalanced prior to recruitment. The researchers will evaluate the effect of each rTMS protocol on training-related motor learning by collecting kinematic and neurophysiological measurements before (pre-training), immediately post-training, and 60 minutes post-training.
Interventions
DEVICErTMS Over Contralateral Hemisphere of Premotor Cortex
This intervention uses rTMS located over the premotor cortex of the contralateral hemisphere (opposite side of the body) to the training wrist. For this intervention the rTMS occurs at a frequency of 0.1 Hz, 50 milliseconds (ms) before the onset of movement-related electromyography (EMG). The MagStim Super Rapid 2 Transcranial Magnetic Stimulator is used.
DEVICErTMS Over Ipsilateral Hemisphere of Premotor Cortex
This intervention uses rTMS located over the premotor cortex of the ipsilateral hemisphere (the same side of the body) to the training wrist. For this intervention the rTMS occurs at a frequency of 0.1 Hz, 50 milliseconds (ms) before the onset of movement-related EMG. The MagStim Super Rapid 2 Transcranial Magnetic Stimulator is used.
DEVICEControl 1: rTMS Timed 400 ms After Movement-related EMG
Control condition 1 uses rTMS over the premotor cortex of the contralateral hemisphere to the training wrist, with a frequency of 0.1 Hz. The rTMS occurs 400 milliseconds (ms) after the onset of movement-related EMG and uses the MagStim Super Rapid 2 Transcranial Magnetic Stimulator.
DEVICEControl 2: rTMS Over the Somatosensory Cortex
This intervention uses rTMS located over the somatosensory cortex of the contralateral hemisphere to the training wrist. For this intervention the rTMS occurs at a frequency of 0.1 Hz, 50 milliseconds (ms) before the onset of movement-related EMG. The MagStim Super Rapid 2 Transcranial Magnetic Stimulator is used.
DEVICEControl 3: Sham rTMS
Control condition 3 uses rTMS located over the premotor cortex of the contralateral hemisphere to the training wrist, at a frequency of 0.1 Hz, 50 milliseconds (ms) before the onset of movement-related EMG. The MagStim Super Rapid 2 Transcranial Magnetic Stimulator with the sham coil is used.
OTHERMotor Training
During motor training, participants will quickly extend their hand at a pace of one extension every 5 seconds (0.2Hz) in response to an auditory cue.
Sponsors
Emory University
American Heart Association
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Participants are randomized to the order in which they receive the five rTMS protocols.
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Have the ability to give informed, written consent * Be aged 55-80 years old * Be right-handed using the Edinburgh handedness inventory * Have intact cognitive abilities, determined by a score higher than the 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) * No current depression, determined by a score less than a 7 on the Hamilton Depression Rating Scale (HDRS) * No neurological disease * No contradictions to Transcranial Magnetic Stimulation (TMS) * TMS over the extensor carpi ulnaris (ECU) hotspot must be able to evoke a motor evoked potential (MEP) in the ECU muscle * MEP amplitude must increase by at least 20% as the TMS intensity increases * Comfortable when receiving TMS of all strengths
Exclusion criteria
* Impaired cognitive abilities, determined by a score less than the 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) * Current depression, determined by a score of more than 7 on the Hamilton Depression Rating Scale (HDRS) * Neurological disease * Has a contradiction to TMS * MEP cannot be evoked with TMS in the ECU muscle * Inability to tolerate one or more TMS strengths
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Primary Motor Cortex (M1) Excitability Derived From Stimulus Response Curve (SRC) | Baseline/Pre-training, Immediately Post-training, 60 Minutes Post-training during each of 5 study visits (up to 217 days) | Functional organization of ipsilateral M1 is assessed by changes in area under the curve of stimulus response curves over the hotspots of an agonist (extensor carpi ulnaris (ECU)) muscle of the training movement. The area under the curve (AUC) was calculated by summing the mean motor evoked potential (MEP) amplitudes per intensity and subject evoked by TMS at intensities 25 -80% maximum stimulator output (MSO), in increments of 5% MSO. The area under the stimulus response curve is normalized to the pre-training measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Reaction Time | Baseline/Pre-training, Immediately Post-training, 60 Minutes Post-training during each of 5 study visits (up to 217 days) | Participants are asked to perform 7 auditory-cued ballistic wrist extensions before and after motor training. Electromyographic (EMG) activity recorded during the ballistic wrist extensions is used to measure reaction time. Reaction time is the length of time between the auditory cue and the onset of the movement-related EMG burst of the extensor carpi ulnaris (ECU) muscle. The change in reaction time from baseline is calculated as the post-training score minus the baseline score. |
| Change in Mean Peak Velocity | Baseline/Pre-training, Immediately Post-training, 60 Minutes Post-training during each of 5 study visits (up to 217 days) | Peak velocity of wrist movement from 6 auditory-paced ballistic wrist extension was collected using a gyrometer. Peak velocity is an assessment of hand motor kinematics. Velocity measures speed in a particular direction of motion. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCathrin Buetefisch, MD, PhD
Emory University
Participant flow
Recruitment details
Participant enrollment began July 7, 2016 and all study visits were completed by November 10, 2019. Participants were enrolled at Emory University in Atlanta, Georgia, USA. The study was suspended for several years and was ultimately terminated in 2024.
Pre-assignment details
Participants were randomized to the order of the 5 different test conditions and each participant had a unique sequence of interventions.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.00 years STANDARD_DEVIATION 5.73 |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
Outcome results
None listed