Paired Associative Stimulation in Stroke

Stroke is the third most common cause of death in the United States after heart disease and cancer. An innovative recovery treatment is in demand for stroke motor recovery. Paired associative stimulation (PAS) is a new technique where one pairs a peripheral stimulation with centrally applied transcranial magnetic stimulation (TMS), and produces plasticity, as measured by TMS motor-evoked potentials (MEP's). The investigators will also compare post-stroke patients to healthy controls on the modulation effect of PAS and motor behavior measures.

Aim1. To investigate whether PAS (PAS25 or PAS10) can modulate motor excitability and plasticity;

Aim2. To investigate whether PAS can modify motor behaviors measures in both post-stroke patients and healthy controls;

Aim3. To investigate whether post-stroke patients show different modulation of PAS on both cortical plasticity and motor behavior measure compared to healthy controls.

For this study the investigators will enroll a total of 10 chronic stroke patients and 10 neurologically healthy controls matched for age and gender. Participants will have 4 visits. The first visit is for screening. They will receive either sham PAS or real PAS25 or real PAS10 at each following treatment visit.

Experimental Methods: Clinical Behavioral Measures: Handgrip; Nine-hole Peg Test; Wolf Motor Function Test; Imaging protocol: T1 weighted anatomical image, fluid attenuation inversion recovery (FLAIR) and diffusion tensor imaging (DTI); Stimulation locations: Left primary motor (M1); right median nerve; PAS methods: TMS stimulation will be delivered at 25 ms or 10 ms or 100 ms after median nerve stimulation.

Inclusion criteria

• 18-80 years old;
• first-ever ischemic stroke involving only one hemisphere;
• Patient demonstrates at least 10 degrees of voluntary finger, thumb and wrist extension; ;
• 6 - 24 months after ischemic stroke

Exclusion criteria

• Primary or secondary intracerebral hematoma, or subarachnoid hemorrhage, or subdural/epidural hematoma;
• Bihemispheric ischemic strokes;
• History of prior stroke or old infarct demonstrated on the CT or MRI or documented in medical records or current on anticoagulant;
• Other concomitant neurological disorders, such as brain tumor, abscess or spinal cord disease affecting upper extremity motor function;
• Documented history of dementia prior to index event;
• Presence of any MRI/TMS risk factors such as (a) an electrically, magnetically or mechanically activated implant including cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system; (b) non-fixed metal in any part of the body, including a previous metallic injury to eye [all jewelry will be removed during stimulation]; (c) pregnancy, since the effect of TMS on the fetus is unknown, females of child bearing age will have to undergo a pregnancy test to confirm eligibility; (d) history of seizure disorder or post-stroke seizures. This last exclusion criterion applies only to the modulation portion of the proposal; (e) median nerve is damaged