Conditions: Stroke
Keywords: Transcranial Magnetic Stimulation Rehabilitation Stroke Plasticity
Allocation: RANDOMIZED | Intervention model: FACTORIAL
Enrollment: 33
Healthy volunteers: yes

Brief summary:
The purpose of this study is to use (Transcranial Magnetic Stimulation) TMS or drugs to improve learning of movement skills and the adaptation processes in patients after stroke. Once investigators have determined the improving effect of TMS and the drugs on learning of movement skills, the study team may be able to provide information that improves rehabilitative treatment and helps to improve recovery after stroke.

Detailed description:
Previous studies have shown, that when patients learn a new motor movement, it may cause a change in the way the nerves act in the area of the brain that controls movement. This change is called use-dependent plasticity. The ability of that part of the brain, called the motor cortex (M1), to reorganize plays a major role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. In this proposed study, investigators will further examine influences of use-dependent plasticity in the non-injured M1 of healthy subjects and injured M1 of stroke subjects using a combination of non-invasive cortical stimulation, medication, and exercise techniques. In Aim 1, investigators will test the effect of drugs that interact specifically with different neurotransmitter systems on use-dependent plasticity in intact M1 of healthy humans. In Aim 2, investigators will identify the parameters for non-invasive transcranial magnetic stimulation (TMS) of M1 that are most effective to enhance use-dependent plasticity in intact healthy human M1. In Aim 3, investigators will test the drugs and rTMS protocols that were demonstrated to be most effective to enhance use- dependent plasticity in the Specific Aim 1 and 2 and apply them to participants who have experienced a stroke. Results from this study will help to inform future research about the efficacy of plasticity enhancing methods in injured M1 of stroke patients.

Arms:
arm 1: Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability. arm 2: Healthy adult female and male subjects will receive repetitive TMS (rTMS) at different times or frequencies with respect to the training movement or sham stimulation. arm 3: Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.

Interventions: intervention 1: Transcranial Magnetic Stimulation (TMS) intervention 2: Carbidopa-Levodopa intervention 3: Methylphenidate intervention 4: Amphetamine Sulfate intervention 5: Placebo intervention 6: Sham Transcranial Magnetic Stimulation (TMS) intervention 7: Transcranial Magnetic Stimulation (TMS) Training
Intervention descriptions: intervention 1: Each TMS training session will begin with a baseline measurement lasting about 30 minutes in which brief magnetic pulses will be generated by the single-pulse and paired pulse TMS stimulator and the responses are recorded with surface EMG electrodes. Participants will be instructed to move their wrist for up to ½ hour. After these measures, rTMS will be applied to the scalp during training. Stimulation will occur at a low rate of different frequencies and different times with respect to the training movement depending on the experimental condition. In the last phase of the session post-training measurements will be done using single TMS pulses. TMS pulses and intensity with be given in random order. intervention 2: Participants will receive one oral dose of carbidopa-levodopa 25mg one hour prior to measuring wrist extension movements.

The order in which Carbidopa-Levodopa is given will be randomized per participant. intervention 3: Participants will receive one oral dose of methylphenidate 40mg 2 hours prior to measuring wrist extension movements.

The order in which Methylphenidate is given will be randomized per participant. intervention 4: Participants will receive one oral dose of amphetamine sulfate 10mg 2 hours prior to measuring wrist extension movements.

The order in which Amphetamine Sulfate is given will be randomized per participant. intervention 5: Participants will receive one oral tablet of placebo 2 hours prior to measuring wrist extension movements.

The order in which Placebo is given will be randomized per participant. intervention 6: Sham TMS pulses will be randomly administered during TMS sessions. intervention 7: TMS surface electromyographic activity will be recorded with surface electrodes mounted on the skin overlaying a forearm muscle. Single pulses of TMS at increasing intensity will be delivered to measure motor cortex excitability. Peak acceleration and TMS evoked responses in the muscle will be measured prior to the training, after completion of the training and again one hour after completion of the training.

Protocol document: