BCI-FES Therapy for Stroke Rehabilitation

Inclusion Criteria:

1. Age18-80 years inclusively at time of consent;

2. Radiologically confirmed stroke, ischemic or intracerebral hemorrhage (ICH) inetiology, with day of onset at least 26 weeks prior to day of randomization

3. Gait velocity<0.8 m/s at screening and baseline visits.

4. Foot-drop in affected limb as defined by dorsiflexion active range of motion (AROM)via goniometry in seated position foot dangling is less than passive range of motionand less than 15 degrees.

5. Plantarflexors spasticity<3 on modified Ashworth Scale;

6. Can walk >10 m (with or without ankle foot orthosis (AFO), and cane or walkerpermitted) at a supervised level;

7. Can tolerate FES with pain no more than 4 on pain analog scale and has adequatemuscle response of dorsiflexion ≥10 degrees;

8. Passive Range of Motion at least 0 degrees ankle dorsiflexion in subtalar neutral orwith FES

Exclusion Criteria:

1. A major, active, coexistent medical, neurological (apart from stroke) or psychiatricdisease (apart from stroke), including alcoholism or dementia, orthopedic injuries,that substantially affects gait. **Because old orthopedic injuries may or may notaffect gait, at the discretion of the site's study PI, exclusion criterion #2related to orthopedic injuries can be waived if the injury was not on the strokeaffected side and the joint/muscles are back to normal motor and range of motionfunction.

2. A major medical disorder that substantially reduces the likelihood that a subjectwill be able to comply with all study procedures or safely complete studyprocedures. This includes, but not limited to documented serious cardiac conditions,serious pulmonary conditions, legal blindness, end stage renal or liver disease,pulmonary embolism or deep venous thrombosis.

3. Resting systolic blood pressure above 170, diastolic blood pressure above 100 atscreening and baseline evaluations

4. Implanted electronic device (e.g. pacemaker) or skull metallic implants (e.g.cranioplasty plate covering the leg motor area);

5. Deficits in communication that interfere with reasonable study participation:language or attention impairment (score>1 on NIH Stroke Scale items 9 and 11,respectively)

6. Significant cognitive impairment, defined as Montreal Cognitive Assessment score < 22 (For those with aphasia: **Because Montreal Cognitive Assessment scores may bedifficult to interpret for patients with aphasia, at the discretion of the site'sstudy PI, exclusion criterion #5 ("MoCA score cannot be <22") can be waived)

7. A new symptomatic stroke occurs apart from the index stroke during the screeningprocess and prior to randomization

8. Life expectancy < 6 months

9. Skin breakdown over electrical stimulation sites;

10. Received chemical denervation (eg Botox) to legs in the preceding 6 months, orexpectation that chemical denervation will be administered to the leg prior toexpected completion of the study

11. Unable or unwilling to perform study procedures/therapy, or expectation ofnon-compliance with study procedures/therapy

12. Pregnancy;

13. Significant pain (visual analog scale >4), chest pain, or shortness of breath withwalking.

14. Receiving any outside concurrent physical therapy involving the lower extremitiesafter enrollment in the study up to 1 month post treatment

15. Any general medical condition and psychosocial situation that substantiallyinterferes with reasonable participate in study appointments

16. Non-English speaking, such that subject does not speak sufficient English to complywith study procedures

17. Concurrent enrollment in another investigational interventional study

18. Severe depression, defined as Geriatric Depression Scale Score >11: **BecauseGeriatric Depression scale scores may be difficult to interpret for some patients,at the discretion of the site's study PI, exclusion criterion #17 ("GeriatricDepression score cannot be >11") can be waived)

19. Concurrent use of FES orthosis for gait.

20. A new symptomatic stroke occurs apart from the index stroke during the screeningprocess and prior to randomization If TMS Eligible (note that potential subjects who do not qualify for TMS will not beexcluded from the main study, they will only be excluded from undergoing TMSprocedures):

21. TMS: Metallic hardware on the scalp (e.g. vascular clips or cranioplasty mesh)

22. TMS: Implanted medication pumps, intracardiac line, or central venous catheter

23. TMS: History of cortical stroke or other cortical lesion such as brain tumor

24. TMS: Prior diagnosis of seizure or epilepsy

25. TMS: Any electrical, mechanical, or magnetic implants

26. TMS: History of neurosurgery

27. TMS: uncontrolled Migraine headaches

28. TMS: Any current medications that affect seizure threshold such as tricyclicantidepressants and neuroleptics

29. TMS: Unstable medical conditions