Neurobiological Principles Applied to the Rehabilitation of Stroke Patients

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.

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.

Eligibility Criteria:
Aims 1 and 2

Inclusion Criteria:

* Normal neurological examination
* Ability to meet criteria of inclusion experiment
* Ability to give informed consent.

Exclusion Criteria:

* History or neurological or psychiatric disease
* Abnormal MRI of brain
* Abnormal neuropsychological testing
* Intake of CNS active drugs
* History of seizure disorder
* History of migraine headaches
* History of anaphylaxis or allergic reactions
* Contraindication to TMS

Aim 3:

Inclusion Criteria:

* Cerebral ischemic infarction more than 6 months prior to entering the study
* Single lesion as defined by MRI of the brain affecting the primary motor output system of the hand at a cortical (M1) level or subcortical level, or unilateral, and supratentorial in absence of history of a previous symptomatic stroke within 3 months of the current stroke
* Dense paresis of the hand for more than three days after cerebral infarction (MRC of \< 4- of wrist- and finger extension/flexion movements)
* Good functional recovery of hand function as defined by MRC of 4 or 4+ of wrist- and finger extension/flexion movements
* Ability to perform wrist extension movements
* Ability to meet criteria of inclusion experiment
* Ability to give informed consent
* Ability of TMS to elicit a measurable MEP of \> 100 μV and an increase in MEP amplitude with increasing stimulus intensity (up to 100% of MSO) of at least 20% over MEP amplitude at MT

Exclusion Criteria:

* History or neurological or psychiatric disease, including bipolar disorder
* Intake of CNS active drugs
* History of seizure disorder
* History of migraine headaches
* History of anaphylaxis or allergic reactions
* Contraindication to TMS