We propose to enhance the effects of brain plasticity using a powerful noninvasive technique for brain modulation consisting of navigated transcranial magnetic stimulation (TMS) priming with transcranial direct current stimulation (tDCS) in combination with motor-training-like constraint-induced movement therapy (CIMT).

Inclusion Criteria:

1. age 18-90
2. first-time clinical ischemic or hemorrhagic cerebrovascular accident as noted in the radiological (or physician's) report;
3. the ability to extend =20° at the wrist and 10° at the metacarpophalangeal and interphalangeal joints of all digits;
4. participants must demonstrate adequate balance while wearing the restraint;
5. the ability to stand from a sitting position and the ability to stand for at least 2 minutes with or without upper extremity support;
6. weakness, defined as score of 15-55 (out of 66) on arm motor Fugl-Meyer (FM) scale; and
7. stroke onset more then 6 months prior to study enrollment.

Exclusion Criteria:

1. significant pre-stroke disability;
2. where applicable (a history of depression before the stroke);
3. any substantial decrease in alertness, language reception, or attention that might interfere with understanding the instructions for the motor testing;
4. excessive pain in any joint of the paretic extremity;
5. contraindications to single-pulse TMS (TMS will be used to measure cortical excitability) such as metal head implants;
6. advanced liver, kidney, cardiac, or pulmonary disease;
7. a terminal medical diagnosis consistent with survival 1 year;
8. coexistent major neurological or psychiatric disease (to decrease the number of confounders);
9. a history of significant drug abuse in the prior 6 months;
10. the use of certain neuropsychotropic drugs such as tricyclics, antidepressants, or 51 of 66 carbamazepine;
11. active enrollment in a separate intervention study targeting stroke recovery; (
12. previously applied constraint-induced motor therapy and/or tDCS treatment for stroke; and
13. a history of epilepsy before stroke (or episodes of seizures within the last six months).

Double (Participant, Outcomes Assessor)