Premotor Cortex: A New Target for Stroke Motor Rehabilitation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Premotor Cortex: A New Target for Stroke Motor Rehabilitation Using Transcranial Magnetic Stimulation

Conditions
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Stroke

Intervention / Treatment
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* Device: rTMS over Premotor Cortex (Contralateral Hemisphere)
* Device: rTMS over Premotor Cortex (Ipsilateral Hemisphere)
* Device: rTMS (Control 1)
* Device: rTMS (Control 2)
* Device: rTMS (Control 3)
* Other: Motor Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Motor training only (pilot participants): Have the ability to give informed, written consent Be aged 18-80 years old Be right-handed using the Edinburgh handedness inventory Have intact cognitive abilities (score higher than 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) No current depression (score less than 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 evoke a motor evoked potential (MEP) in the ECU muscle MEP amplitude must increase by at least 20% as the TMS intensity increases The subjects must be comfortable when receiving TMS of all strengths. Remaining study participants: 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 (score higher than 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) No current depression (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 The subjects must be comfortable when receiving TMS of all strengths. Exclusion Criteria: Impaired cognitive abilities (score lesser than 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) Current depression (score 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single motor training only<br>For a pilot experiment, healthy, right-handed subjects will complete one testing session. During the testing session, subjects will complete motor training. The results of this experiment will determine the motor training protocol used in the main experiment. | Other: Motor Training<br>* 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.<br>|
| Experimental: Repetitive TMS during motor training<br>Healthy, right-handed subjects will complete five testing sessions. During each testing session, subjects will complete motor training while receiving one of five repetitive transcranial magnetic stimulation (rTMS) protocols. Subjects will receive a different rTMS protocol at each testing session. By the end of the study, each subject will have received all rTMS protocols. | Device: rTMS over Premotor Cortex (Contralateral Hemisphere)<br>* Location of rTMS: premotor cortex Frequency of rTMS: 0.1 Hz Time of rTMS: 50 milliseconds before the onset of movement-related EMG Device: MagStim Super Rapid 2 Transcranial Magnetic Stimulator<br>Device: rTMS over Premotor Cortex (Ipsilateral Hemisphere)<br>* Location of rTMS: premotor cortex Frequency of rTMS: 0.1 Hz Time of rTMS: 50 milliseconds before the onset of movement-related EMG Device: Super Rapid 2 Transcranial Magnetic Stimulator<br>Device: rTMS (Control 1)<br>* Location of rTMS: premotor cortex Frequency of rTMS: 0.1 Hz Time of rTMS: 400 milliseconds after the onset of movement-related EMG Device: Super Rapid 2 Transcranial Magnetic Stimulator<br>Device: rTMS (Control 2)<br>* Location of rTMS: somatosensory cortex Frequency of rTMS: 0.1 Hz Time of rTMS: 50 milliseconds before the onset of movement-related EMG Device: Super Rapid 2 Transcranial Magnetic Stimulator<br>Device: rTMS (Control 3)<br>* Location of rTMS: premotor cortex Frequency of rTMS: 0.1 Hz Time of rTMS: 50 milliseconds before the onset of movement-related EMG Device: Super Rapid 2 Transcranial Magnetic Stimulator with Sham Coil<br>Other: Motor Training<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in wrist acceleration | The subjects will be asked to perform 7 isometric wrist extensions before and after motor training. Wrist acceleration will be measured by a gyroscope taped to the dorsum of the subject's hand undergoing motor training. An increase in the maximum acceleration that persists at least an hour after training is indicative of motor learning. We will compare the effect of the rTMS protocols on the change in the wrist acceleration associated with motor learning (baseline to post 1 min, baseline to post 30 mins, baseline to post 60 mins). | Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training) | 
| Change in stimulus response curve (SRC) | The stimulus response curve (SRC) is a set of motor evoked potentials (MEPs) collected in response to transcranial magnetic stimulation (TMS) pulses of increasing intensities. The SRC can characterize input-output parameters of the corticospinal tract and organization of the primary motor cortex. A change in the SRC parameters after training will reflect a change in the organization of the primary motor cortex associated with motor learning. We will compare the effect of the rTMS protocols on the change in the SRC parameters associated with motor learning (baseline to post 1 min, baseline to post 30 mins, baseline to post 60 mins). | Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training) | 
| Change in short interval intracortical inhibition (SICI) | Short interval intracortical inhibition (SICI) is an inhibitory phenomenon in the motor cortex. To test for SICI, a sub-threshold conditioning stimulus (CS) will precede a supra-threshold test stimulus (TS) by 2 milliseconds (ms). The amplitude of a conditioned TS-evoked MEP will be expressed as a percent of the amplitude of an unconditioned TS-evoked MEP. A decrease in the percent MEP after training would indicate a increase in SICI. An increase in the percent MEP after training would indicate a decrease in SICI. We will compare the effect of the rTMS protocols on the change in SICI associated with motor learning (baseline to post 1 min, baseline to post 30 mins, baseline to post 60 mins). | Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in wrist force | The subjects will be asked to perform 7 isometric wrist extensions before and after motor training. A force transducer transducer will record the maximum force produced during the wrist extensions. | Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training) | 
| Change in reaction time | Subjects will be asked to perform 7 auditory-cued ballistic wrist extensions before and after motor training. Electomyographic (EMG) activity recorded during the ballistic wrist extensions will be 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. | Baseline and post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training) | 
| Change in task accuracy | Task accuracy will be determined by the number of successful trials over the number of total trials. A trial will be considered successful when the subject moves a cursor from the home position into a target box by modulating the acceleration of their wrist. An increase in task accuracy after training will indicate motor learning. | Baseline and post-motor training (1 minute after completion of motor training) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation