Monoaminergic DriveEffect of Neural Constraints on Movement in Stroke

Inclusion Criteria:

• History of unilateral supratentorial ischemic stroke that occurred at least six months prior to enrollment
• Age between 18-80
• Paresis confined to one side, with substantial motor impairment of the upper limb and some residual voluntary movement (Upper Extremity Fugl-Meyer Assessment in the range of 10-50/66)
• Ability to communicate, understand, and provide informed consent
• Ability to elevate their limb against gravity up to at least 75 degrees of shoulder flexion and to generate active elbow extension
• MRI compatible
• Intact skin on the hemiparetic arm
• Ability to sit for three hours.

Exclusion Criteria:

• Motor or sensory impairment in the non-affected limb (FMA<66, filament >3.6)
• Any brainstem and/or cerebellar lesion
• untreated cardiovascular disease
• History of neurologic disorder other than stroke that affects the arms
• Any acute or chronic painful condition in the upper extremities or spine, indicated by a score ≥5 on a 10-point visual analog scale
• Current use of a pacemaker
• History of seizure
• Chemo denervation: botulinum toxin injection to any portion of the paretic upper extremity within the last 6 months, or phenol/alcohol injections <12 months before participation
• Flexion contractures larger than 30 degrees in the elbow, wrist, metacarpophalangeal joints (MCP) and interphalangeal joints (IP) after stretching for 15 minutes
• Current participation in any experimental rehabilitation or drug studies
• Individuals with any known contraindications to Tizanidine or currently taking Tizanidine; - concurrent use of medications known to suppress central nervous system activity
• pregnant women or women who are nursing.

Additionally, each participant will be asked to provide a list of their current medications and a medical screening questionnaire will be sent to their primary physician. Each participant's list of medications will be reviewed for possible interactions with the study drugs and, at the study physician's advice, will be excluded from the study or asked to withhold medications when applicable. A full list of potential drug interactions can be seen in "Medication Interactions", but concisely includes the following: medications with dopaminergic, serotonergic, or noradrenergic actions; central nervous system (CNS) depressants; antihypertensive/ antiarrhythmic agents; and hormonal medications/contraceptives.