Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional

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.
    

Intervention name(s): Transcranial Magnetic Stimulation (TMS); Carbidopa-Levodopa; Methylphenidate; Amphetamine Sulfate; Placebo; Sham Transcranial Magnetic Stimulation (TMS); Transcranial Magnetic Stimulation (TMS) Training
Intervention type(s): Other; Drug; Drug; Drug; Drug; Other; Other
Intervention description(s): 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.; 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.; 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.; 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.; 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.; Sham TMS pulses will be randomly administered during TMS sessions.; 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.
Other intervention name(s): Sinemet
Intervention MeSH terms: Levodopa; Carbidopa; Carbidopa, levodopa drug combination; Methylphenidate; Amphetamine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Transcranial Magnetic Stimulation; Rehabilitation; Stroke; Plasticity